Patent application title: IMMUNOGENIC COMPOSITION FOR USE IN VACCINATION AGAINST STAPHYLOCOCCEI
Inventors:
Cindy Castado (Rixensart, BE)
Cindy Castado (Rixensart, BE)
Nicolas Pierre Fernand Lecrenier (Rixensart, BE)
Cecile Anne Neyt (Rixensart, BE)
Jan Poolman (Rixensart, BE)
IPC8 Class: AA61K39085FI
USPC Class:
4241391
Class name: Drug, bio-affecting and body treating compositions immunoglobulin, antiserum, antibody, or antibody fragment, except conjugate or complex of the same with nonimmunoglobulin material binds antigen or epitope whose amino acid sequence is disclosed in whole or in part (e.g., binds specifically-identified amino acid sequence, etc.)
Publication date: 2015-11-19
Patent application number: 20150328302
Abstract:
The present application relates to immunogenic compositions comprising a
mixture of staphylococcal antigens which combines antigen having
different functions, for instance, combinations including a
staphylococcal extracellular component binding protein and a
staphylococcal transporter protein or a staphylococcal extracellular
component binding protein and a staphylococcal regulator of virulence or
toxin or a staphylococcal transporter protein and a staphylococcal
regulator of virulence or toxin. Vaccines, methods of treatment, uses of
and processes to make a staphylococcal vaccine are also described.Claims:
1. An immunogenic composition comprising at least two different proteins
or immunogenic fragments thereof selected from at least two groups of
proteins or immunogenic fragments selected from the following groups:
Group a) at least one staphylococcal extracellular component binding
protein or immunogenic fragment thereof selected from the group
consisting of SdrG, laminin receptor, EbhA, EbhB, Elastin binding protein
(EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrH, Lipase GehD, FnbA,
FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP,
Vitronectin binding protein, coagulase, and MAP; Group b) at least one
staphylococcal transporter protein or immunogenic fragment thereof
selected from the group consisting of immunodominant ABC transporter,
IsdA, IsdB, Mg2+ transporter, SitC and Ni ABC transporter; Group c) at
least one staphylococcal regulator of virulence, toxin or immunogenic
fragment thereof selected from the group consisting of alpha toxin (Hla),
alpha toxin H35R mutant, alpha toxin H35L mutant and RNA III activating
protein (RAP).
2. The immunogenic composition of claim 1 wherein at least one protein or immunogenic fragment is selected from group a).
3. The immunogenic composition of claim 1 wherein at least one protein or immunogenic fragment is selected from group b).
4. The immunogenic composition of claim 1 wherein at least one protein or immunogenic fragment is selected from group c).
5. The immunogenic composition of claim 1 4 wherein at least one protein or immunogenic fragment is selected from group a), group b) and group c).
6. The immunogenic composition of claim 1 comprising at least one protein or immunogenic fragment from S. Aureus.
7. The immunogenic composition of claim 1 comprising at least one protein or immunogenic fragment from S. Epidermidis.
8. The immunogenic composition of claim 1 further comprising a PIA polysaccharide or oligosaccharide.
9. The immunogenic composition of claim 1 further comprising type V and/or type VIII capsular polysaccharide or oligosaccharide from S. Aureus.
10. The immunogenic composition of claim 1 further comprising Type I, and/or Type II and/or Type III capsular polysaccharide or oligosaccharide from S. Epidermidis.
11-12. (canceled)
13. The immunogenic composition of claim 8 wherein a staphylococcal capsular polysaccharide is conjugated to a protein carrier.
14. (canceled)
15. The immunogenic composition of claim 13 wherein the protein carrier is selected from the group consisting of tetanus toxic, diphtheria toxic, CRM197, Haemophilus influenzae protein D, pneumolysin and alpha toxic.
16. The immunogenic composition of claim 1 which is capable of generating an effective immune response against both S. Aureus and S. Epidermidis.
17. A vaccine comprising the immunogenic composition of claim 1 and a pharmaceutically acceptable excipient.
18. A method of making a vaccine comprising the steps of mixing antigens to make the immunogenic composition of claim 1 and adding a pharmaceutically acceptable excipient.
19. A method of preventing or treating staphylococcal infection comprising the step of administering the vaccine of claim 17 to a patient in need thereof.
20. (canceled)
21. A method of preparing an immune globulin for use in prevention or treatment of staphylococcal infection comprising the steps of immunizing a recipient with the vaccine of claim 17 and isolating the immune globulin from the recipient.
22. An immune globulin prepared by the method of claim 21.
23. A pharmaceutical composition comprising the immune globulin of claim 22 and a pharmaceutically acceptable excipient.
24. A method for treatment or prevention of staphylococcal infection comprising a step of administering to a patient an effective amount of the pharmaceutical composition of claim 23.
25. (canceled)
26. A pharmaceutical composition comprising two or more monoclonal antibodies or fragments thereof which are reactive against at least two constituents of the immunogenic composition of claim 1 wherein the at least two constituents are selected from at least 2 of groups a), b), and c).
Description:
STATEMENT REGARDING SEQUENCE LISTING
[0001] The Sequence Listing associated with this application is provided in text format in lieu of a paper copy and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is 400077--412C1_SEQUENCE_LISTING.txt. The text file is 499 KB, was created on Mar. 16, 2015, and is being submitted electronically via EFS-Web.
BACKGROUND
[0002] 1. Technical Field
[0003] The present invention relates to the field of Staphylococcal immunogenic compositions and vaccines, their manufacture and the use of such compositions in medicine. More particularly, it relates to vaccine compositions comprising a combination of antigens for the treatment or prevention of staphylococcal infection. Methods of using such vaccines in medicine and methods for their preparation are also provided.
[0004] 2. Description of the Related Art
[0005] The number of both community acquired and hospital acquired infections have increased over recent years with the increased use of intravascular devices. Hospital acquired (nosocomial) infections are a major cause of morbidity and mortality, more particularly in the U.S., where if affects more than 2 million patients annually. Following various studies, about 6 percent of the U.S. patients will acquire an infection during their stay in hospital. The economic burden in the USA was estimated to be more than $4.5 billion in 1992 (Emori and Gaynes, 1993, Clin. Microbiol. Rev. 6; 428). The most frequent infections are urinary tract infections (UTI-33% of the infections), followed by pneumonia (15.5%), surgical site infections (14.8%) and primary bloodstream infections (13%) Emori and Gaynes, 1993, Clin. Microbiol. Rev. 6; 428).
[0006] Staphylococcus aureus, Coagulase-negative Staphylococci (mostly Staphylococcus epidermidis), enterococcus spp, Escherichia coli and Pseudomonas aeruginosa are the major nosocomial pathogens. Although those pathogens almost cause the same number of infections, the severity of the disorders they can produce combined with the frequency of antibiotic resistant isolates balance this ranking towards S. aureus and S. epidermidis as being the most significant nosocomial pathogens.
[0007] Staphylococcus aureus is the most common cause of nosocomial infections with a significant morbidity and mortality (Romero-Vivas et al., 1995, Infect. Dis. 21; 1417). It is the cause of some cases of osteomyelitis, endocarditis, septic arthritis, pneumonia, abscesses and toxic shock syndrome.
[0008] S. epidermidis is a normal skin commensal which is also an important opportunistic pathogen responsible for infections of implanted medical devices and infections at sites of surgery. Medical devices infected by S. epidermidis include cardiac pacemakers, cerebrospinal fluid shunts, continuous ambulatory peritoneal dialysis catheters, orthopedic devices and prosthetic heart valves.
[0009] S. aureus and S. epidermidis infections are treated with antibiotics with penicillin being the drug of choice whereas vancomycin is used for methicillin resistant isolates. The percentage of staphylococcal strains exhibiting wide-spectrum resistance to antibiotics has become increasingly prevalent since the 1980's (Panlilo et al., 1992, Infect. Control. Hosp. Epidemiol. 13; 582), posing a threat for effective antimicrobial therapy. In addition, the recent emergence of vancomycin resistant S. aureus strain has aroused fear that methicillin resistant S. aureus strains will emerge and spread for which no effective therapy is available.
[0010] An alternative approach of using antibodies against staphylococcal antigens in passive immunotherapy has been investigated. Therapy involving administration of polyclonal antisera is under development (WO 00/15238, WO 00/12132) as well as treatment with a monoclonal antibody against lipoteichoic acid (WO 98/57994).
[0011] An alternative approach would be use of active vaccination to generate an immune response against staphylococci. Several candidates for inclusion as vaccine components have been identified. These include Fibronectin binding protein (U.S. Pat. No. 5,840,846), MHC II analogue (U.S. Pat. No. 5,648,240), fibrinogen binding protein (U.S. Pat. No. 6,008,341), GehD (US 2002/0169288), collagen binding protein (U.S. Pat. No. 6,288,214), SdrF, SdrG and SdrH (WO 00/12689), mutant SEA and SEB exotoxins (WO 00/02523) and 52 kDa vitronectin binding protein (WO 01/60852).
[0012] The S. aureus genome has been sequenced and many of the coding sequences have been identified (EP786519, WO02/094868). The same is true for S. epidermidis (WO 01/34809). As a refinement of this approach, others have identified proteins that are recognized by hyperimmune sera from patients who have suffered staphylococcal infection (WO01/98499, WO 02/059148).
[0013] The first generation of vaccines targeted against S. aureus or against the exoproteins it produces have met with limited success (Lee 1996 Trends Microbiol. 4; 162). There remains a need to develop effective vaccines against staphylococcal infections.
BRIEF SUMMARY
[0014] Accordingly the present invention provides an immunogenic composition comprising at least two different proteins or immunogenic fragments thereof, selected from at least two groups of proteins or immunogenic fragments selected from the following groups:
[0015] Group a) at least one staphylococcal extracellular component binding protein or immunogenic fragment thereof selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, fig and MAP;
[0016] Group b) at least one staphylococcal transporter protein or immunogenic fragment thereof selected from the group consisting of Immunodominant ABC transporter, IsdA, IsdB, Mg2+transporter, SitC and Ni ABC transporter;
[0017] Group c) at least one staphylococcal regulator of virulence, toxin or immunogenic fragment thereof selected from the group consisting of alpha toxin (H1a), alpha toxin H35R mutant, RNA III activating protein (RAP).
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIGS. 1A-1M--Polypeptide sequences of preferred proteins. Table 1 provides information on which protein is represented by each SEQ ID.
[0019] FIGS. 2A-2KK--Nucleotide sequences encoding preferred proteins. Table 1 provides information on which protein is encoded by each SEQ ID.
[0020] FIG. 3 (Panel A and Panel B)--Purification of alpha toxin under native conditions. Panel A shows a Coomassie stained SDS-PAGE of samples prepared during the purification of alpha toxin. Lane 1--molecular weight markers, lane 2--soluble fraction containing over-expressed alpha toxin, lane 3--flow through from the Ni-NTA column, lane 4--fractions eluted with 10% buffer B, lane 5--fractions eluted with 20% buffer B, lane 6--fractions eluted with 30% buffer B, lane 7--fractions eluted with 50% buffer B, lane 8--fractions eluted with 75% buffer B, lane 9 and 10 fractions eluted with 100% buffer B, lane 11 bacteria at T=0 before induction, lane 12--bacteria at T=4 hours after induction, lane 13--cell lysate, lane 14--soluble fraction, lane 15--insoluble fraction.
[0021] Panel B shows a Coomassie stained SDS-PAGE of 10, 5, 2 and 1 μl of the purified alpha toxin.
[0022] FIG. 4 (Panel A and Panel B)--Purification of SdrC under denaturing conditions. Panel A shows a Coomassie stained SDS-PAGE of samples prepared during the purification of alpha toxin. Lane M--molecular weight markers, lane Start--supernatant formed from the insoluble fraction containing over-expressed SdrC, lane FT1--flow through from the Ni-NTA column, lane C--fractions eluted with wash buffer C, lane D--fractions eluted with buffer D, lane E--fractions eluted with buffer E.
[0023] Panel B shows a Coomassie stained SDS-PAGE of 1, 2, 5 and 10 μl of the purified SdrC.
[0024] FIGS. 5A-5O--ELISA results for antisera against staphylococcal proteins in plates coated with purified proteins.
[0025] Pool mice pre--result using pooled sera extracted from mice pre-inoculation. Pool mice Post III--result using pooled mouse sera extracted post-immunization. Pool rabbit pre--result using pooled sera extracted from rabbits pre-inoculation. Pool rabbit Post III--result using pooled rabbit sera extracted post-immunization. Blc-negative control.
[0026] FIGS. 6A-6E--ELISA results for mouse antisera raised against staphylococcal proteins in plates coated with killed staphylococci.
[0027] Panel A uses plates coated with S. aureus serotype 5 killed whole cells. Panel B uses plates coated with S. aureus serotype 8 killed whole cells. Panel C uses plates coated with S. epidermidis killed whole cells.
[0028] The line marked with square signs shows the ELISA result using antisera from mice immunized three times with the indicated staphylococcal protein. The line marked with diamond signs shows the ELISA result for pre-immune mouse sera.
[0029] FIGS. 7A-7H--ELISA results for rabbit antisera raised against staphylococcal proteins in plates coated with killed staphylococci.
[0030] Panel A uses plates coated with S. aureus serotype 5 killed whole cells. Panel B uses plates coated with S. aureus serotype 8 killed whole cells. Panel C uses plates coated with S. epidermidis killed whole cells.
[0031] The line marked with square signs shows the ELISA result using antisera from rabbits immunized three times with the indicated staphylococcal protein (except for HarA where only one immunization was given). The line marked with diamond signs shows the ELISA result for pre-immune rabbit sera.
DETAILED DESCRIPTION
[0032] The present invention discloses particular combinations of Staphylococcal antigens which when combined, lead to the production of an immunogenic composition that is effective at treating or preventing staphylococcal infection. Immunogenic compositions of the invention suitably incorporate antigens which are involved in different staphylococcal functions. Such immunogenic compositions target the immune response towards different aspects of the staphylococcal function and are therefore able to induce a particularly effective immune response.
[0033] Staphylococcal infections progress through several different stages. For example, the staphylococcal life cycle involves commensal colonization, initiation of infection by accessing adjoining tissues or the bloodstream, anaerobic multiplication in the blood, interplay between S. aureus virulence determinants and the host defense mechanisms and induction of complications including endocarditis, metastatic abscess formation and sepsis syndrome. Different molecules on the surface of the bacterium will be involved in different steps of the infection cycle. By targeting the immune response against an effective amount of a combination of particular antigens involved in different processes of Staphylococcal infection, a Staphylococcal immunogenic composition or vaccine with increased efficacy can be achieved.
[0034] In particular, combinations of certain antigens from different classes, some of which are involved in adhesion to host cells, some of which are involved in iron acquisition or other transporter functions, some of which are toxins or regulators of virulence and immunodominant antigens can elicit an immune response which protects against multiple stages of infection.
[0035] The effectiveness of the immune response can be measured either in animal model assays as described in the examples and/or using an opsonophagocytic assay as described in the examples.
[0036] An additional advantage of the invention is that the combination of antigens of the invention from different families of proteins in an immunogenic composition will enable protection against a wider range of strains.
[0037] The invention relates to immunogenic compositions comprising a plurality of proteins selected from at least two different categories of protein, having different functions within Staphylococci. Examples of such categories of proteins are extracellular binding proteins, transporter proteins such as Fe acquisition proteins, toxins or regulators of virulence and other immunodominant proteins. The vaccine combinations of the invention are effective against homologous Staphylococcal strains (strains from which the antigens are derived) and preferably also against heterologous Staphylococcal strains.
[0038] An immunogenic composition of the invention comprises a number of proteins equal to or greater than 2, 3, 4, 5 or 6 selected from 2 or 3 of the following groups:
[0039] group a)--at least one staphylococcal extracellular component binding protein or immunogenic fragment thereof selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, fig and MAP;
[0040] group b)--at least one staphylococcal transporter protein or immunogenic fragment thereof selected from the group consisting of Immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC and Ni ABC transporter;
[0041] group c)--at least one staphylococcal regulator of virulence, toxin or immunogenic fragment thereof selected from the group consisting of alpha toxin (H1a), alpha toxin H35R mutant, RNA III activating protein (RAP).
[0042] For example a first protein is selected from group a), b) or c) and a second protein is selected from a group selected from groups a), b) and c) which does not include the second protein.
[0043] In a preferred embodiment, the immunogenic composition of the invention contains at least one protein selected from group a) and an additional protein selected from group b) and/or group c).
[0044] In a further embodiment, the immunogenic composition of the invention contains at least one antigen selected from group b) and an additional protein selected from group c) and/or group a).
[0045] In a further embodiment, the immunogenic composition of the invention contains at least one antigen selected from group c) and an additional protein selected from group a) and/or group b).
[0046] The immunogenic composition of the invention suitably contains proteins from S. aureus, and/or S. epidermidis.
Proteins
[0047] Immunogenic compositions of the invention comprise an isolated protein which comprises an amino acid sequence which has at least 85% identity, preferably at least 90% identity, more preferably at least 95% identity, most preferably at least 97-99% or exact identity, to that of any sequence of FIG. 1.
[0048] Where a protein is specifically mentioned herein, it is preferably a reference to a native or recombinant, full-length protein or optionally a mature protein in which any signal sequence has been removed. The protein may be isolated directly from the staphylococcal strain or produced by recombinant DNA techniques. Immunogenic fragments of the protein may be incorporated into the immunogenic composition of the invention. These are fragments comprising at least 10 amino acids, preferably 20 amino acids, more preferably 30 amino acids, more preferably 40 amino acids or 50 amino acids, most preferably 100 amino acids, taken contiguously from the amino acid sequence of the protein. In addition, such immunogenic fragments are immunologically reactive with antibodies generated against the Staphylococcal proteins or with antibodies generated by infection of a mammalian host with Staphylococci. Immunogenic fragments also includes fragments that when administered at an effective dose, (either alone or as a happen bound to a carrier), elicit a protective immune response against Staphylococcal infection, more preferably it is protective against S. Aureus and/or S. Epidermidis infection. Such an immunogenic fragment may include, for example, the protein lacking an N-terminal leader sequence, and/or a trans membrane domain and/or a C-terminal anchor domain. In a preferred aspect the immunogenic fragment according to the invention comprises substantially all of the extracellular domain of a protein which has at least 85% identity, preferably at least 90% identity, more preferably at least 95% identity, most preferably at least 97-99% identity, to that a sequence selected from FIG. 1 over the entire length of the fragment sequence.
[0049] Also included in immunogenic compositions of the invention are fusion proteins composed of Staphylococcal proteins, or immunogenic fragments of staphylococcal proteins. Such fusion proteins may be made recombinant and may comprise one portion of at least 2, 3, 4, 5 or 6 staphylococcal proteins. Alternatively, a fusion protein may comprise multiple portions of at least 2, 3, 4 or 5 staphylococcal proteins. These may combine different Staphylococcal proteins or immunogenic fragments thereof in the same protein. Alternatively, the invention also includes individual fusion proteins of Staphylococcal proteins or immunogenic fragments thereof, as a fusion protein with heterologous sequences such as a provider of T-cell epitopes or purification tags, for example: β-galactosidase, glutamine-S-transferase, green fluorescent proteins (GAP), epitope tags such as FLAG, my tag, poly histidine, or viral surface proteins such as influenza virus hem agglutinin, or bacterial proteins such as tetanus toxic, diphtheria toxic, CRAM197.
TABLE-US-00001 TABLE 1 The following table sets out the SEQ ID numbers of preferred protein sequences and DNA sequences that are found in FIG. 1 and FIG. 2, respectively. SA indicates a sequence from S. aureus and SE indicates a sequence from S. epidermidis. Name Protein sequence DNA sequence Immunodominant ABC transporter SA SEQ ID 1 SEQ ID 34 SE SEQ ID 2 SEQ ID 35 Laminin receptor SA SEQ ID 3 SEQ ID 36 SE SEQ ID 4 SEQ ID 37 Secretory Antigen A Ssa SA 1 SEQ ID 5 SEQ ID 38 SA 2 SEQ ID 6 SEQ ID 39 SE SEQ ID 7 SEQ ID 40 SitC SA SEQ ID 8 SEQ ID 41 SE SEQ ID 9 SEQ ID 42 IsaA/PisA (IssA) SA SEQ ID 10 SEQ ID 43 SE SEQ ID 11 SEQ ID 44 EbhA/B SA EbhA SEQ ID 12 SEQ ID 45 SA EbhB SEQ ID 13 SEQ ID 46 SE EbhA SEQ ID 14 SEQ ID 47 SE EbhB SEQ ID 15 SEQ ID 48 Accumulation-assoc pro Aap SA SEQ ID 16 SEQ ID 49 SE SEQ ID 17 SEQ ID 50 RNA III activating protein RAP SA SEQ ID 18 SEQ ID 51 SE SEQ ID 19 SEQ ID 52 FIG/SdrG SA SEQ ID 20 SEQ ID 53 SE SEQ ID 21 SEQ ID 54 Elastin binding protein EbpS SA SEQ ID 22 SEQ ID 55 SE SEQ ID 23 SEQ ID 56 Extracellular protein EFB SA SEQ ID 24 SEQ ID 57 alpha toxin SA SEQ ID 25 SEQ ID 58 SBI SA SEQ ID 26 SEQ ID 59 IsdA SA SEQ ID 27 SEQ ID 60 IsdB SA SEQ ID 28 SEQ ID 61 SdrC SA SEQ ID 29 SEQ ID 62 ClfA SA SEQ ID 30 SEQ ID 63 FnbA SA SEQ ID 31 SEQ ID 64 ClfB SA SEQ ID 32 SEQ ID 65 Coagulase SA SEQ ID 33 SEQ ID 66 FnbB SA SEQ ID 67 SEQ ID 71 MAP SA SEQ ID 68 SEQ ID 72 SdrC SA SEQ ID 69 SEQ ID 73 SdrG SA SEQ ID 70 SEQ ID 74
Extracellular Component Binding Proteins
[0050] Extracellular component binding proteins are proteins that bind to host extracellular components. The term includes, but is not limited to adhesions.
[0051] Examples of extracellular component binding proteins include laminin receptor (Naiad et al., J. Med. Microbiol. 1992, 36; 177), SitC/MntC/saliva binding protein (U.S. Pat. No. 5,801,234, Wilts hire and Foster, Infect. Immune. 2001, 69; 5198), EbhA (Williams et al., Infect. Immune. 2002, 70; 6805), EbhB, Elastin binding protein (EbpS) (Park et al., 1999, J. Biol. Them. 274; 2845), EFB (FIB) (Wasteful and Flock, 1995, J. Clin. Microbiol. 33; 2347), SBI (Hang et al., FEMS Immune. Med. Microbiol. 2000, 28; 211), autolysin (Rump et al., 2001, J. Infect. Dis. 183; 1038), ClfA (U.S. Pat. No. 6,008,341, McDevitt et al., Mol. Microbiol. 1994, 11; 237), SdrC, SdrG (McCrea et al., Microbiology 2000, 146; 1535), SdrH (McCrea et al., Microbiology 2000, 146; 1535), Lipase GehD (US2002/0169288), SasA, FnbA (Flock et al., Mol Microbiol. 1994, 12; 599, U.S. Pat. No. 6,054,572), FnbB (WO 97/14799, Booth et al., 2001 Infect. Immune. 69; 345), collagen binding protein Cna (Visai et al., 2000, J. Biol. Chem. 275; 39837), ClfB (WO 99/27109), FbpA (Phonimdaeng et al., 1988 J. Gen Microbiol. 134; 75), Npase (Flock 2001 J. Bacteriol. 183; 3999), IsaA/PisA (Lonenz et al., FEMS Immuno. Med. Microbiol. 2000, 29; 145), SsaA (Lang et al., FEMS Immunol. Med. Microbiol. 2000, 29; 213), EPB (Hussain and Hermann symposium on Staph Denmark 14-17th 2000), SSP-1 (Veenstra et al., 1996, J. Bacteriol. 178; 537), SSP-2 (Veenstra et al., 1996, J. Bacteriol. 178; 537), 17 kDa heparin binding protein HBP (Fallgren et al., 2001, J. Med. Microbiol. 50; 547), Vitronectin binding protein (Li et al., 2001, Curr. Microbiol. 42; 361), fibrinogen binding protein, coagulase, Fig (WO 97/48727) and MAP (U.S. Pat. No. 5,648,240).
SitC/MntC/Saliva Binding Protein
[0052] This is an ABC transporter protein which is a homologue of adhesin PsaA in S. pneumoniae. It is a highly immunogenic 32 kDa lipoprotein which is distributed through the bacterial cell wall (Cockayne et al., Infect. Immune. 1998 66; 3767). It is expressed in S. Aureus and S. Epidermidis as a 32 kDa lipoprotein and a 40 kDa homologue is present in S. hominis. In S. Epidermidis, it is a component of an iron-regulated operon. It shows considerable homology to both adhesions including FimA of Streptococcus parasanguis, and with lipoproteins of a family of ABC transporters with proven or putative metal iron transport functions. Therefore SitC is included as an extracellular binding protein and as a metal ion transporter.
[0053] The saliva binding protein disclosed in U.S. Pat. No. 5,801,234 is also a form of SitC and can be included in an immunogenic composition of the invention.
ClfA and ClfB
[0054] Both these proteins have fibrinogen binding activity and trigger S. Aureus to form clumps in the presence of plasma. They contain a LPXTG motif common to wall associated proteins.
[0055] ClfA is described in U.S. Pat. No. 6,008,341 and ClfB is described in WO 99/27109.
Coagulase (FbpA)
[0056] This is a fibrinogen binding protein which triggers S. Aureus to form clumps in the presence of plasma. It is described in references related to Coagulase: Phonimdaeng et al., (J. Gen. Microbiol. 1988, 134:75-83), Phonimdaeng et al., (Mol, Microbiol, 1990; 4:393-404), Cheung et al. (Infect. Immune. 1995; 63:1914-1920) and Shopsin et al. (J. Clin. Microbiol. 2000; 38:3453-3456).
[0057] Preferred fragments for inclusion in the immunogenic composition of the invention include the mature protein in which the signal peptide has been removed (amino acids 27 to the C-terminus).
[0058] Coagulase has three distinct domains. Amino acids 59-297 which is a coiled coil region, amino acids 326-505 which is a proline and glycine rich region and the C-terminal domain from amino acid 506 to 645 which has a beta sheet conformation. Each of these domains is a preferred fragment of the invention.
SdrG-Fbe--EfB/FIG
[0059] Fbe is a fibrinogen binding protein that is found in many isolates of S. Epidermidis and has a deduced molecular weight of 119 kDa (Nilsson et al., 1998. Infect. Immune. 66; 2666). Its sequence is related to that of clumping factor from S. Aureus (ClfA). Antibodies against Fbe can block the binding of S. Epidermidis to fibrinogen coated plates and to catheters (Pei and Flock, 2001, J. Infect. Dis. 184; 52). This protein is also described as SdrG in WO 00/12689. SdrG is found in coagulase negative staphylococci and is a cell wall associated protein containing a LPXTG sequence.
[0060] SdrG contains a signal peptide (amino acids 1-51), a region containing fibrinogen binding sites and collagen binding sites (amino acids 51-825), two CnaB domains (amino acids 627-698 and 738-809), a SD repeat region (amino acids 825-1000) and an anchor domain (amino acids 1009-1056).
[0061] Fbe has a putative signal sequence with a cleavage site between amino acids 51 and 52. Therefore a preferred fragment of Fbe contains the mature form of Fbe extending from amino acid 52 to the C-terminus (amino acid 1,092).
[0062] The domain of Fbe from amino acid 52 to amino acid 825 is responsible for fibrinogen binding. Therefore a preferred fragment of Fbe consists of or contains amino acids 52-825.
[0063] The region between amino acid 373 and 516 of Fbe shows the most conservation between Fbe and ClfA. Preferred fragment will therefore contain amino acids 373-516 of Fbe.
[0064] Amino acids 825-1041 of Fbe contains a highly repetitive region composed of tandemly repeated aspartic acid and serine residues.
[0065] Preferred fragments of SdrG include polypeptides in which the signal peptide and/or the SD repeats and the anchor domain have been removed. These include polypeptides comprising or consisting of amino acids 50-825, amino acids 50-633, amino acids 50-597 (SEQ ID NO 2 of WO 03/76470), amino acids 273-597 (SEQ ID NO 4 of WO 03/76470), amino acids 273-577 (SEQ ID NO 6 of WO 03/76470) amino acids 1-549, amino acids 219-549, amino acids 225-549, amino acids 219-528, amino acids 225-528 of SEQ ID NO:70.
[0066] Preferably, an SdrG polypeptide having a sequence at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or 100% homologous to the sequence of SEQ ID 70, 20 or 21 is incorporated into the immunogenic composition of the invention.
[0067] The compositions of the invention optionally comprise a fragment of the SdrG polypeptides described above.
[0068] Preferred fragments have the signal peptide and/or the SD repeat domain and/or the anchoring domain deleted. For example sequences corresponding to amino acids 1-713 , 1-549, 225-549, 225-529, 24-717, 1-707, 1-690, 1-680, 1-670, 1-660, 1-650, 1-640, 1-630, 1-620, 1-610, 1-600, 34-707, 44-697, 36-689 of SEQ ID 76 or sequences having 85%, 90%, 92%, 95%, 97%, 98%, 99% or 100% identity to SEQ ID NO:70 or 20 or 21.
[0069] Preferred fragment with the signal peptide deleted have a methionine residue at the N-terminus of the fragment to ensure correct translation.
[0070] A more preferred fragment has the following sequence (SEQ ID NO: 75):
TABLE-US-00002 MEENSVQDVKDSNTDDELSDSNDQSSDEEKNDVINNNQSINTDDNNQ IIKKEETNNYDGIEKRSEDRTESTTNVDENEATFLQKTPQDNTHLTE EEVKESSSVESSNSSIDTAQQPSHTTINREESVQTSDNVEDSHVSDF ANSKIKESNTESGKEENTIEQPNKVKEDSTTSQPSGYTNIDEKISNQ DELLNLPINEYENKARPLSTTSAQPSIKRVTVNQLAAEQGSNVNHLI KVTDQSITEGYDDSEGVIKAHDAENLIYDVTFEVDDKVKSGDTMTVD IDKNTVPSDLTDSFTIPKIKDNSGEIIATGTYDNKNKQITYTFTDYV DKYENIKAHLKLTSYIDKSKVPNNNTKLDVEYKTALSSVNKTITVEY QRPNENRTANLQSMFTNIDTKNHTVEQTIYINPLRYSAKETNVNISG NGDEGSTIIDDSTIIKVYKVGDNQNLPDSNRIYDYSEYEDVTNDDYA QLGNNNDVNINFGNIDSPYIIKVISKYDPNKDDYTTIQQTVTMQTTI NEYTGEFRTASYDNTIAFSTSSGQGQGDLPPEKTYKIGDYVWEDVDK DGIQNTNDNEKPLSNVLVTLTYPDGTSKSVRTDEDGKYQFDGLKNGL TYKITFETPEGYTPTLKHSGTNPALDSEGNSVWVTINGQDDMTIDSG FYQTPKYSLGNYVWYDTNKDGIQGDDEKGISGVKVTLKDENGNIIST TTTDENGKYQFDNLNSGNYIVHFDKPSGMTQTTTDSGDDDEQDADGE EVHVTITDHDDFSIDNGYYDDE
EbhA and EbhB
[0071] EbhA and EbhB are proteins that are expressed in both S. aureus and S. epidermidis (Clarke and Foster. Infect. Immun. 2002, 70; 6680, Williams et al., Infect. Immun. 2002, 20; 6805) and which bind to fibronectin. Since fibronectin is an important component of extracellular matrix, EbhA and EbhB have an important function in adhering staphylococci to host extracellular matrix.
[0072] The Ebh proteins are large, having a molecular weight of 1.1 megadaltons. It is advantageous to use a fragment of the Ebh protein rather than the complete sequence due to ease of production and formulation. The central region of the protein contains imperfect repeats which contain fibronectin binding sites. Fragments containing one or more of the repeat domains described below are preferred fragments for incorporation into the immunogenic composition of the invention.
[0073] Ebh proteins contain imperfect repeats units of 127 amino acids in length which are characterized by containing the consensus sequence:
TABLE-US-00003 (SEQ ID NO: 152) L.G.{ 10}A.{ 13}Q.{ 26}L...M..L.{ 33}A Preferably (SEQ ID NO: 153) .{ 19}L.G.{ 10}A.{ 13}Q.{ 26}L...M..L.{ 33}A.{ 12} More preferably (SEQ ID NO: 154) .....I/V..A...I/V..AK.ALN/DG..NL..AK..A.{ 6}L..LN. AQK..L..QI/V..A..V..V.{ 6}A..LN/D.AM..L...I/V. D/E...TK.S.NY/F.N/DAD..K..AY/F..AV..A..I/V. N/D.......
[0074] Where `.` means any amino acid and `.{10}` means any 10 amino acids and I/V indicates alternative choices of amino acid.
[0075] By reference to the sequence disclosed in Kuroda et al., (2001) Lancet 357; 1225-1240, and Table 2, the repeat sequences within Ebh proteins are readily deduced.
[0076] Preferred fragments to be included in the immunogenic composition of the invention include polypeptides containing of one, two, three, four, five, six, seven, eight, nine, ten or more than 10 of the 127 amino acid repeat units. Such fragments may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more repeats of the 127 amino acid repeat region or may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more repeats with additional amino acid residues present at either or both ends of the fragment. A further preferred fragment is the H2 polypeptide of about 44 kDa spanning three repeats (amino acids 3202-3595) as described in Clarke et al., Infection and Immunity 70, 6680-6687, 2002. Such fragments will preferably be able to bind fibronectin and/or to elicit antibodies that are reactive against the whole Ebh protein.
[0077] The Ebh polypeptides are capable of binding to fibronectin. Preferred fragments of these polypeptides sequences retain the ability to bind to fibronectin. Binding to fibronectin can be assessed by ELISA as described by Clarke et al. (Infection and Immunity 70; 6680-6687, 2002).
[0078] Still further preferred fragments are those which comprise a B-cell or T-helper epitope, for example those fragments/peptides described in Tables 3 and 4.
TABLE-US-00004 TABLE 2 Repeat sequences in the full-length sequence of Ebh. The full-length sequence of Ebh is disclosed in Kuroda et al., (2001) Lancet 357; 1225-1240. The following table shows the amino acid residues at which the 127 amino acid repeats begin and end within the full length sequence. Begin End 1 3204 3330 2 3331 3457 3 3457 3583 4 3583 3709 5 3709 3835 6 3835 3961 7 3961 4087 8 4200 4326 9 4326 4452 10 4452 4578 11 4578 4704 12 4704 4830 13 4830 4956 14 4956 5082 15 5082 5208 16 5208 5334 17 5334 5460 18 5460 5586 19 5585 5711 20 5711 5837 21 5837 5963 22 5963 6089 23 6089 6215 24 6215 6341 25 6341 6467 26 6467 6593 27 6593 6719 28 6719 6845 29 6845 6971 30 6971 7097 31 7097 7223 32 7223 7349 33 7349 7475 34 7475 7601 35 7601 7727 36 7727 7853 37 7852 7978 38 7978 8104 39 8104 8230 40 8230 8356 41 8356 8482 42 8482 8608 43 8604 8730 44 8858 8984
TABLE-US-00005 TABLE 3 B-cell epitope prediction for a 127 amino acid repeat: The full-length sequence is disclosed in Kuroda et al., (2001) Lancet 357; 1225-1240. One of these repeats, encoded by amino acids 3204-3331 of the full-length sequence was chosen to carry out an epitope prediction:- (SEQ ID NO: 76) MDVNTVNQKAASVKSTKDALDGQQNLQRAKTEATNAITHASDLNQ AQKNALTQQVNSAQNVHAVNDIKQTTQSLNTAMTGLKRGVANHNQ VVQSDNYVNADTNKKNDYNNAYNHANDIINGNAQHPVI Begin End Epitope sequence Start Stop 5 10 TVNQKA 3208 3213 (SEQ ID NO: 77) 14 19 KSTKDA 3217 3222 (SEQ ID NO: 78) 21 33 DGQQNLQRAKTEA 3224 3236 (SEQ ID NO: 79) 42 51 DLNQAQKNAL 3245 3254 (SEQ ID NO: 80) 66 74 DIKQTTQSL 3269 3277 (SEQ ID NO: 81) 100 112 ADTNKKNDYNNAY 3303 3315 (SEQ ID NO: 82) 117 123 DIINGNA 3320 3326 (SEQ ID NO: 83)
[0079] The "Begin" and "End" columns present the position of the predicted B-cell epitopes in the 127 amino acid repeat.
[0080] The "Start" and "Stop" columns present the position of the predicted B-cell epitopes in the Ebh full length sequence.
TABLE-US-00006
[0080] TABLE 4 T-helper cell epitope prediction in Ebh: The full-length sequence is disclosed in TrEMBL database, sequence reference Q8NWQ6. One of these repeats, encoded by amino acids 3204-3331 of the full-length sequence was chosen to carry out an epitope prediction:- (SEQ ID NO: 84) MDVNTVNQKAASVKSTKDALDGQQNLQRAKTEATNAITHASDLNQAQ KNALTQQVNSAQNVHAVNDIKQTTQSLNTAMTGLKRGVANHNQVVQS DNYVNADTNKKNDYNNAYNHANDIINGNAQHPVI Position Position repeat Epitope sequence sequence 1 MDVNTVNQK (SEQ ID NO: 85) 3204 3 VNTVNQKAA (SEQ ID NO: 86) 3206 6 VNQKAASVK (SEQ ID NO: 87) 3209 26 LQRAKTEAT (SEQ ID NO: 88) 3229 37 ITHASDLNQ (SEQ ID NO: 89) 3240 43 LNQAQKNAL (SEQ ID NO: 90) 3246 51 LTQQVNSAQ (SEQ ID NO: 91) 3254 55 VNSAQNVHA (SEQ ID NO: 92) 3258 61 VHAVNDIKQ (SEQ ID NO: 93) 3264 64 VNDIKQTTQ (SEQ ID NO: 94) 3267 67 IKQTTQSLN (SEQ ID NO: 95) 3270 74 LNTAMTGLK (SEQ ID NO: 96) 3277 78 MTGLKRGVA (SEQ ID NO: 97) 3281 81 LKRGVANHN (SEQ ID NO: 98) 3284 85 VANHNQVVQ (SEQ ID NO: 99) 3288 91 VVQSDNYVN (SEQ ID NO: 100) 3294 92 VQSDNYVNA (SEQ ID NO: 101) 3295 97 YVNADTNKK (SEQ ID NO: 102) 3301 98 VNADTNKKN (SEQ ID NO: 103) 3302 108 YNNAYNHAN (SEQ ID NO: 104) 3311 112 YNHANDIIN (SEQ ID NO: 105) 3315 118 IINGNAQHP (SEQ ID NO: 106) 3321 119 INGNAQHPV (SEQ ID NO: 107) 3322
[0081] The "Position repeat" column presents the position of the predicted T-cell epitopes in the repeat.
[0082] The "Position sequence" column presents the position of the predicted T-cell epitopes in the Ebh full length sequence.
[0083] Fragments of the polypeptides of the invention may be employed for producing the corresponding full-length polypeptide by peptide synthesis; therefore, these fragments may be employed as intermediates for producing the full-length polypeptides of the invention.
[0084] Particularly preferred are variants in which several, 5-10, 1-5, 1-3, 1-2 or 1 amino acids are substituted, deleted, or added in any combination.
Elastin Binding Protein (EbpS)
[0085] EbpS is a protein containing 486 amino acids with a molecular weight of 83 kDa. It is associated with the cytoplasmic membrane of S. Aureus and has three hydrophobic regions which hold the protein in the membrane (Downer et al., 2002, J. Biol. Them. 277; 243; Park et al., 1996, J. Biol. Them. 271; 15803).
[0086] Two region between amino acids 1-205 and 343-486 are surface exposed on the outer face of the cytoplasmic membrane. The ligand binding domain of EbpS is located between residues 14-34 at the N-terminus (Park et al., 1999, J. Biol. Them. 274; 2845).
[0087] A preferred fragment to be incorporated into the immunogenic composition of the invention would be the surface exposed fragment containing the elastin binding region (amino acids 1-205). Some preferred fragments do not contain the entire exposed loop but should contain the elastin binding region (amino acids 14-34). An alternative fragment which could be used consists of amino acids forming the second surface exposed loop (amino acids 343-486). Alternative fragments containing up to 1, 2, 5, 10, 20, 50 amino acids less at one or both ends are also possible.
Laminin Receptors
[0088] The laminin receptor of S. Aureus plays an important role in pathogenicity. A characteristic feature of infection is bloodstream invasion which allows widespread metastatic abscess formation. Bloodstream invasion requires the ability to extravasate across the vascular basement membrane. This is achieved through binding to laminin through the laminin receptor (Lopes et al., Science 1985, 229; 275).
[0089] Laminin receptors are surface exposed and are present in many strains of staphylococci including S. Aureus and S. Epidermidis.
Sbi
[0090] Sbi is a protein having an IgG binding region and an apolipoprotein H binding domain and it is expressed in most strains of S. Aureus (Hang et al., 1998, Microbiology 144; 985).
[0091] The N-terminus of the sequence of Sbi has a typical signal sequence with a cleavage site after amino acid 29. Therefore a preferred fragment of Sbi to be incorporated into an immunogenic composition of the invention starts at amino acid residue 30, 31, 32 or 33 and continues to the C-terminus of Sbi, for example of SEQ ID NO: 26.
[0092] The IgG binding domain of Sbi has been identified as a region towards the N-terminus of the protein from amino acids 41-92. This domain is homologous to the IgG binding domains of protein A.
[0093] The minimal IgG binding domain of Sbi contains the following sequence (SEQ ID NO: 108):
TABLE-US-00007 QTTQNNYVTDQQKAFYQVLHLKGITEEQRNQYIKTLREHP ** *** * *** * * * ERAQEVFSESLK * * *- denotes amino acids which are similar between IgG binding domains
[0094] Preferred fragment of Sbi to be included in the immunogenic composition of the invention contains an IgG binding domain. This fragment contains the consensus sequence for an IgG binding domain as designated by * as shown in the above sequence. Preferably the fragment contains or consists of the complete sequence shown above. More preferably, the fragment contains or consists of amino acids 30-92, 33-92, 30-94, 33-94, 30-146, 33-146, 30-150, 33-150, 30-160, 33-160, 33-170, 33-180, 33-190, 33-200, 33-205 or 33-210 of Sbi, for example of SEQ ID NO:26.
[0095] Preferred fragment may contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 amino acid substitutions from the sequences indicated.
[0096] Preferred fragments may contain multiple repeats (2, 3, 4, 5, 6, 7, 8, 9 or 10) of the IgG binding domain.
Efb-Fib
[0097] Fib is a 19 kDa fibrinogen binding protein which is secreted into the extracellular medium by S. Aureus. It is produced by all S aureus isolates tested (Wasteful and Flock 1995, J. Clin. Microbiol. 33; 2347).
[0098] S. Aureus clumps in the presence of fibrinogen and binds to fibrinogen coated surfaces. This ability facilitates staphylococcal colonization of catheters and endothelial cells.
[0099] Fib contains a signal sequence at the N-terminus of the protein with a putative cleavage site at about amino acid 30. Therefore a preferred fragment to be introduced in the immunogenic composition of the invention would contain the sequence of the mature protein (from about amino acid 30 to the C-terminus of the protein).
IsaA/PisA
[0100] IsaA is a 29 kDa protein, also known as PisA has been shown to be a immunodominant staphylococcal protein during sepsis in hospital patients (Lorenz et al., 2000, FEMS Immunol. Med. Microb. 29; 145).
[0101] The first 29 amino acids of the IsaA sequence are thought to be a signal sequence. Therefore a preferred fragment of IsaA to be included in an immunogenic composition of the invention would contain amino acid residues 30 onwards, to the end of the coded sequence.
Fibronectin Binding Protein
[0102] Fibronectin binding protein A (FnbA) is described in U.S. Pat. No. 5,320,951 and Schennings et al., (1993, Microb. Pathog. 15; 227). Fibronectin binding protein A contains several domains that are involved in binding to fibronectin (WO 94/18327). These are called D1, D2, D3 and D4. Preferred fragments of fibronectin binding protein A or B comprise or consist of D1, D2, D3, D4, D1-D2, D2-D3, D3-D4, D1-D3, D2-D4 or D1-D4 (as described in WO 94/18327).
[0103] Fibronectin binding protein contains a 36 amino acid signal sequence. For example:
TABLE-US-00008 (SEQ ID NO: 109) VKNNLRYGIRKHKLGAASVFLGTMIVVGMGQDKEAA
[0104] Optionally, the mature protein omitting this signal sequence is included in the immunogenic composition of the invention.
Transporter Proteins
[0105] The cell wall of Gram positive bacteria acts as a barrier preventing free diffusion of metabolites into the bacterium. A family of proteins orchestrates the passage of essential nutrients into the bacterium and are therefore essential for the viability of the bacterium. The term transporter protein covers proteins involved in the initial step of binding to metabolites such as iron as well as those involved in actually transporting the metabolite into the bacterium.
[0106] Molecular iron is an essential co-factor for bacterial growth. Siderophores are secreted that bind free iron and then are captured by bacterial surface receptors that deliver iron for transport across the cytoplasmic membrane. Iron acquisition is critical for the establishment of human infections so that the generation of an immune response against this class of proteins leads to a loss of staphylococcal viability.
[0107] Examples of transporter proteins include Immunodominant ABC transporter (Burnie et al., 2000 Infect. Immune. 68; 3200), IsdA (Mazmanian et al., 2002 PNAS 99; 2293), IsdB (Mazmanian et al., 2002 PNAS 99; 2293), Mg2+ transporter, SitC (Wilts hire and Foster 2001 Infect. Immune. 69; 5198) and Ni ABC transporter.
Immunodominant ABC Transporter
[0108] Immunodominant ABC transporter is a well conserved protein which may be capable of generating an immune response that is cross-protective against different staphylococcal strains (Mei et al., 1997, Mol. Microbiol. 26; 399). Antibodies against this protein have been found in patients with septicemia (Burnie et al., 2000, Infect. Immune. 68; 3200).
[0109] Preferred fragments of immunodominant ABC transporter will include the peptides DRHFLN, GNYD, RRYPF, KTTLLK, GVTTSLS, VDWLR, RGFL, more preferably KIKVYVGNYDFWYQS, TVIVVSHDRHFLYNNV and/or TETFLRGFLGRMLFS (SEQ ID NOS: 110-119 respectively) since these sequences contain epitopes that are recognized by the human immune system.
IsdA-IsdB
[0110] The isd genes (iron-regulated surface determinant) of S. Aureus encode proteins responsible for hemoglobin binding and passage of heme iron to the cytoplasm, where it acts as an essential nutrient. IsdA and IsdB are located in the cell wall of staphylococci. IsdA appear to be exposed on the surface of bacterium since it is susceptible to proteinase K digestion. IsdB was partially digested suggesting that it is partially exposed on the surface of the bacterium (Mazmanian et al., 2003 Science 299; 906).
[0111] IsdA and IsdB are both 29 kDa proteins which bind heme. Their expression is regulated by the availability of iron via the Fur repressor. Their expression will be high during infection in a host where the concentration of iron will be low.
[0112] They are also known as FrpA and FrpB (Morrissey et al., 2002, Infect. Immune. 70; 2399). FrpA and FrpB are major surface proteins with a high charge. They have been shown to provide a major contribution to adhesion to plastic.
[0113] In an embodiment, the immunogenic composition of the invention comprises a fragment of IsdA and/or IsdB which is described in WO 01/98499 or WO 03/11899.
Toxins and Regulators of Virulence
[0114] Members of this family of proteins include toxin such as alpha toxin, hemolysin, enterotoxin B and TSST-1 as well as proteins that regulate the production of toxins such as RAP.
Alpha Toxin (H1a)
[0115] Alpha toxin is an important virulence determinant produced by most strains of S. Aureus. It is a pore forming toxin with hemolytic activity. Antibodies against alpha toxin have been shown to neutralize the detrimental and lethal effects of alpha toxin in animal models (Adlam et al., 1977 Infect. Immune. 17; 250). Human platelets, endothelial cells and mononuclear cells are susceptible to the effects of alpha toxin.
[0116] The high toxicity of alpha toxin requires that it should be detoxified before being used as an immunogen. This can be achieved by chemical treatment, for instance by treating with formaldehyde, glutaraldehyde of other cross-linking reagents or by chemically conjugating it to bacterial polysaccharides as described below.
[0117] A further way of removing toxicity is to introduce point mutations that remove toxicity while retaining the antigenicity of the toxin. The introduction of a point mutation at amino acid 35 of alpha toxin where a histidine residue is replaced with a leucine residue results in the removal of toxicity whilst retaining immunogenicity (Menzies and Kernodle 1996; Infect. Immune. 64; 1839). Histidine 35 appears to be critical for the proper oligomerization required for pore formation and mutation of this residue leads to loss of toxicity.
[0118] When incorporated into immunogenic compositions of the invention, alpha toxin is preferably detoxified by mutation of His 35, most preferably by replacing His 35 with Leu or Arg. In an alternative embodiment, alpha toxin is detoxified by conjugation to other components of the immunogenic composition, preferably capsular polysaccharides, most preferably to S. Aureus type V polysaccharide and/or S. Aureus Type VIII polysaccharide and/or PNAG.
RNA III Activating Protein (RAP)
[0119] RAP is not itself a toxin, but is a regulator of the expression of virulence factors. RAP is produced and secreted by staphylococci. It activates the agr regulatory system of other staphylococci and activates the expression and subsequent release of virulence factors such as hemolysin, enterotoxin B and TSST-1.
[0120] An immune response generated against RAP would not kill the bacterium but would interfere with their pathogenicity. This has the advantage of providing less selective pressure for new resistant strains to emerge.
[0121] It would have a second advantage of producing an immune response that would be instrumental in reducing the morbidity of the infection.
[0122] It is particularly advantageous to combine RAP with other antigens in a vaccine, particularly where the additional antigen would provide an immune response that is able to kill the bacterium.
Other Proteins
Accumulation-Associated Protein (Aap)
[0123] Aap is a 140 kDa protein which is essential for the accumulation of S. Epidermidis strains on surfaces (Hussain et al., Infect. Immune. 1997, 65; 519). Strains expressing this protein produced significantly larger amounts of biofilm and Aap appear to be involved in biofilm formation. Antibodies against Aap are able to inhibit biofilm formation and inhibit the accumulation of S. Epidermidis.
[0124] A preferred fragment of Aap is a conserved domain comprising or consisting of amino acids 550-1069.
Staphylococcal Secretory Antigen SsaA
[0125] SsaA is a strongly immunogenic protein of 30 kDa found in both S. Aureus and S. Epidermidis (Lang et al., 2000 FEMS Immunol. Med. Microbiol. 29; 213). Its expression during endocarditis suggested a virulence role specific to the pathogenesis of the infectious disease.
[0126] SsaA contains an N-terminal leader sequence and a signal peptidase cleavage site. The leader peptide is followed by a hydrophilic region of approximately 100 amino acids from residue 30 to residue 130.
[0127] A preferred fragment of SsaA to be incorporated into the immunogenic composition of the invention is made up of the mature protein (amino acids 27 to the C-terminus or amino acids 30 to the C-terminus).
[0128] A further preferred fragments contains the hydrophilic area of SsaA from amino acid 30 to amino acid 130.
Preferred Combinations
[0129] A preferred combination of proteins in the immunogenic composition of the invention comprises laminin receptor and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0130] A further preferred combination of proteins in the immunogenic composition of the invention comprises SitC and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0131] A further preferred combination of proteins in the immunogenic composition of the invention comprises EbhA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0132] A further preferred combination of proteins in the immunogenic composition of the invention comprises EbhB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0133] A further preferred combination of proteins in the immunogenic composition of the invention comprises EbpS and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0134] A further preferred combination of proteins in the immunogenic composition of the invention comprises EFB(FIB) and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0135] A further preferred combination of proteins in the immunogenic composition of the invention comprises SBI and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0136] A further preferred combination of proteins in the immunogenic composition of the invention comprises autolysin and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0137] A further preferred combination of proteins in the immunogenic composition of the invention comprises ClfA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0138] A further preferred combination of proteins in the immunogenic composition of the invention comprises SdrC and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0139] A further preferred combination of proteins in the immunogenic composition of the invention comprises SdrG and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant and RAP.
[0140] A further preferred combination of proteins in the immunogenic composition of the invention comprises SdrH and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0141] A further preferred combination of proteins in the immunogenic composition of the invention comprises Lipase GehD and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0142] A further preferred combination of proteins in the immunogenic composition of the invention comprises SasA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0143] A further preferred combination of proteins in the immunogenic composition of the invention comprises FnbA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0144] A further preferred combination of proteins in the immunogenic composition of the invention comprises FnbB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0145] A further preferred combination of proteins in the immunogenic composition of the invention comprises Cna and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0146] A further preferred combination of proteins in the immunogenic composition of the invention comprises ClfB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0147] A further preferred combination of proteins in the immunogenic composition of the invention comprises FbpA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0148] A further preferred combination of proteins in the immunogenic composition of the invention comprises Npase and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0149] A further preferred combination of proteins in the immunogenic composition of the invention comprises IsaA/PisA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0150] A further preferred combination of proteins in the immunogenic composition of the invention comprises SsaA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0151] A further preferred combination of proteins in the immunogenic composition of the invention comprises EPB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0152] A further preferred combination of proteins in the immunogenic composition of the invention comprises SSP-1 and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0153] A further preferred combination of proteins in the immunogenic composition of the invention comprises SSP-2 and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0154] A further preferred combination of proteins in the immunogenic composition of the invention comprises HPB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0155] A further preferred combination of proteins in the immunogenic composition of the invention comprises vitronectin binding protein and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0156] A further preferred combination of proteins in the immunogenic composition of the invention comprises fibrinogen binding protein and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0157] A further preferred combination of proteins in the immunogenic composition of the invention comprises coagulase and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0158] A further preferred combination of proteins in the immunogenic composition of the invention comprises Fig and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0159] A further preferred combination of proteins in the immunogenic composition of the invention comprises MAP and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0160] A further preferred combination of protein in the immunogenic composition of the invention comprises immunodominant ABC tranporter and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0161] A further preferred combination of protein in the immunogenic composition of the invention comprises IsdA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0162] A further preferred combination of protein in the immunogenic composition of the invention comprises IsdB and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0163] A further preferred combination of protein in the immunogenic composition of the invention comprises SitC and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, alpha toxin, alpha toxin H35L OR H35R mutant, RAP, Aap and SsaA.
[0164] A further preferred combination of protein in the immunogenic composition of the invention comprises alpha toxin and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.
[0165] A further preferred combination of protein in the immunogenic composition of the invention comprises alpha toxin H35L OR H35R variant and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.
[0166] A further preferred combination of protein in the immunogenic composition of the invention comprises RAP and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.
[0167] A further preferred combination of protein in the immunogenic composition of the invention comprises Aap and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, RAP, alpha toxin and H35L OR H35R alpha toxin.
[0168] A further preferred combination of protein in the immunogenic composition of the invention comprises SsaA and 1, 2, 3, 4 or 5 further antigens selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, immunodominant ABC transporter, IsdA, IsdB, Mg2- transporter, SitC, Ni ABC transporter, RAP, alpha toxin and H35L OR H35R alpha toxin.
[0169] The inventors have demonstrated that certain antigens produce a particularly effective immune response within the context of a mixture of antigens. Accordingly, an embodiment of the invention is an immunogenic composition comprising IsaA and a staphylococcal transporter protein, or IsaA and a staphylococcal regulator of virulence or toxin, or comprising Sbi and a staphylococcal transporter protein, or Sbi and a staphylococcal regulator of virulence or toxin, or comprising SdrC and a staphylococcal transporter protein, or SdrC and a staphylococcal regulator of virulence or toxin, or IsaA and Sbi, or IsaA and SdrC, or IsaA and autolysin, or IsaA and Ebh, or Sbi and SdrC, or Sbi and Autolysin, or Sbi and Ebh, or SdrC and autolysin, or SdrC and Ebh, or Autolysin-glucosaminidase and Ebh. For each of these combinations, the proteins may be full length or fragments, having sequences at least 85%, 90%, 95%, 98% or 100% identical to that of the sequences of FIG. 1.
[0170] In the above and below combinations, the specified proteins may optionally be present in the immunogenic composition of the invention as a fragment or fusion protein as described above.
[0171] Preferred immunogenic compositions of the invention do not include the protein sequences disclosed in WO02/094868.
Combinations of Three Proteins
[0172] A preferred immunogenic composition of the invention contains three protein components in a combination of alpha-toxin, an extracellular component binding protein (preferably an adhesin) and a transporter protein (preferably an iron-binding protein).
[0173] In such a combination, the alpha toxin may be chemically detoxified or genetically detoxified by introduction of point mutation(s), preferably the His35Leu point mutation. The alpha toxin is present as a free protein or alternatively is conjugated to a polysaccharide or LTA component of the immunogenic composition.
[0174] Preferred combinations include:
[0175] An immunogenic composition comprising alpha toxin, IsdA and an extracellular component binding protein selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.
[0176] An immunogenic composition comprising alpha toxin, IsdB and an extracellular component binding protein selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.
[0177] An immunogenic composition comprising alpha toxin, IsdA and an adhesin selected from the group consisting of laminin receptor, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), ClfA, SdrC, SdrG, SdrH, autolysin, FnbA, FnbB, Cna, ClfB, FbpA, Npase, SSP-1, SSP-2, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.
[0178] An immunogenic composition comprising alpha toxin, IsdB and an adhesin selected from the group consisting of laminin receptor, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), autolysin, ClfA, SdrC, SdrG, SdrH, FnbA, FnbB, Cna, ClfB, FbpA, Npase, SSP-1, SSP-2, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP.
[0179] An immunogenic composition comprising alpha toxin, IsdA and laminin receptor.
[0180] An immunogenic composition comprising alpha toxin, IsdA and EbhA.
[0181] An immunogenic composition comprising alpha toxin, IsdA and EbhB.
[0182] An immunogenic composition comprising alpha toxin, IsdA and EbpS.
[0183] An immunogenic composition comprising alpha toxin, IsdA and EFB (FIB).
[0184] An immunogenic composition comprising alpha toxin, IsdA and SdrG.
[0185] An immunogenic composition comprising alpha toxin, IsdA and ClfA.
[0186] An immunogenic composition comprising alpha toxin, IsdA and ClfB.
[0187] An immunogenic composition comprising alpha toxin, IsdA and FnbA.
[0188] An immunogenic composition comprising alpha toxin, IsdA and coagulase.
[0189] An immunogenic composition comprising alpha toxin, IsdA and Fig.
[0190] An immunogenic composition comprising alpha toxin, IsdA and SdrH.
[0191] An immunogenic composition comprising alpha toxin, IsdA and SdrC.
[0192] An immunogenic composition comprising alpha toxin, IsdA and MAP.
[0193] An immunogenic composition comprising IsaA and Sbi.
[0194] An immunogenic composition comprising IsaA and IsdB.
[0195] An immunogenic composition comprising IsaA and IsdA.
[0196] An immunogenic composition comprising IsaA and SdrC.
[0197] An immunogenic composition comprising IsaA and Ebh or fragment thereof as described above.
[0198] An immunogenic composition comprising Sbi and SdrC.
[0199] An immunogenic composition comprising Sbi and Ebh or fragment thereof as described above.
[0200] An immunogenic composition of the invention comprising IsaA, Sbi or SdrC.
Selection of Antigens Expressed in Different Clonal Lineages
[0201] Analysis of the occurrence of virulence factors in relation with the population structure of Staphylococcus aureus showed variable presence of virulence genes in natural populations of S. Aureus.
[0202] Among clinical isolates of Staphylococcus aureus, at least five clonal lineages were shown to be highly prevalent (Booth et al., 2001 Infect. Immune. 69(1):345-52). Alpha-hemolysin (hla), fibronectin-binding protein A (fnbA) and clumping factor A (clfA) were shown to be present in most of the isolates, regardless of lineage identity, suggesting an important role of these proteins in the survival of S. Aureus (Booth et al., 2001 Infect. Immune. 69(1):345-52). Moreover, according to Peacock et al. 2002 the distributions of fnbA, clfA, coagulase, spa, map, pvl (Panton-Valentine leukocidin), hlg (gamma-toxin), alpha-toxin and ica appeared to be unrelated to the underlying clonal structure suggesting considerable horizontal transfer of these genes.
[0203] In contrary, other virulence genes such as fibronectin binding protein B (fnbB), beta-hemolysin (hlb), collagen binding protein (cna), TSST-1 (tst) and methicillin resistance gene (mecA) are strongly associated with specific lineages (Booth et al., 2001 Infect. Immune. 69(1):345-52). Similarly, Peacock et al. 2002 (Infect Immune. 70(9):4987-96) showed that the distributions of the enterotoxins, tst, the exfolatins (eta and etb), beta-and delta-toxins, the sdr genes (sdrD, sdrE and bbp), cna, ebpS and efb within the population are all highly significantly related to MLST-derived clonal complexes.
[0204] MLST data provide no evidence that strains responsible for nosocomial disease represent a distinct subpopulation from strains causing community-acquired disease or strains recovered from asymptomatic carriers (Feil et al., 2003 J. Bacteriol. 185(11):3307-16).
[0205] Preferred immunogenic compositions of the invention are effective against staphylococci from different clonal lineages.
[0206] In one embodiment, this is achieved by including 1, 2, 3, 4, preferably at least 1 protein that is expressed in most isolates of staphylococci. Examples of such proteins include alpha-hemolysin (hla), fibronectin-binding protein A (fnbA) and clumping factor A (clfA), coagulase, spa, map, pvl (Panton-Valentine leukocidin), hlg (gamma-toxin) and ica. We have also identified immunodominant ABC transporter, RAP, autolysin (Rump et al., 2001, J. Infect. Dis. 183; 1038), laminin receptors, SitC, IsaA/PisA, SPOIIIE ( ) SsaA, EbpS, SasF (Roche et al 2003, Microbiology 149; 643), EFB(FIB), SBI, ClfB, IsdA, IsdB, FnbB, Npase, EBP, Bone sialo binding protein II, IsaB/PisB (Lorenz et al., FEMS Immuno. Med. Microb. 2000, 29; 145), SasH (Roche et al., 2003, Microbiology 149; 643), MRPI, SasD (Roche et al., 2003, Microbiology 149; 643), SasH (Roche et al., 2003, Microbiology 149; 643), aureolysin precursor (AUR)/Sepp1and novel autolysin.
[0207] In an alternative embodiment, 2 or more proteins which are expressed in different sets of clonal strains are included in the immunogenic composition of the invention. Preferably the combination of antigens will allow an immune response to be generated that is effective against multiple clonal strains, most preferably against all clonal stains. Preferred combinations include FnbB and beta-hemolysin, FnbB and Cna, FnbB and TSST-1, FnbB and mecA, FnbB and SdrD, FnbB and SdrF, FnbB and EbpS, FnbB and Efb, beta-hemolysin and Cna, beta-hemolysin and TSST-1, beta-hemolysin and mecA, beta-hemolysin and SdrD, beta-hemolysin and SdrF, beta-hemolysin and EbpS, beta-hemolysin and Efb, Cna and TSST-1, Cna and mecA, Cna and SdrD, Cna and SdrF, Cna and EbpS, Cna and Efb, TSST-1 and mecA, TSST-1 and SdrD, TSST-1 and SdrF, TSST-1 and EbpS, TssT-1 and Efb, MecA and SdrD, MecA and SdrF, MecA and EbpS, MecA and Efb, SdrD and SdrF, SdrD and EbpS, SdeD and Efb, SdrF and EbpS, SdrF and Efb, and, EbpS and Efb.
[0208] The preferred combinations described above may be combined with additional components described below.
Selection of Antigens Expressed During Different Growth Phases
[0209] Staphylococci go through an exponential growth phase during which a particular set of proteins will be expressed. These include many of the extracellular component binding proteins and transporter proteins. After a period of exponential growth, the staphylococci revert to a post-exponential phase during which growth is slower and protein expression is modulated. Many of the proteins expressed during the exponential growth phase are down regulated whereas other proteins, such as enzymes and most toxins, including alpha toxin, are expressed at higher levels.
[0210] Preferred immunogenic compositions of the invention comprise a protein expressed at higher levels during the exponential growth phase and a protein expressed at higher levels during the post-exponential phase.
[0211] `Higher levels` refers to the level of expression being higher in one phase in comparison with the other phase.
[0212] In a preferred embodiment, the immunogenic composition of the invention comprises alpha toxin and an extracellular component binding protein (preferably FnbA, FnbB, ClfA and ClfB) or a transporter protein.
[0213] More preferably it comprises alpha toxin or Cna or Lipase GehD and a protein selected from the group consisting of laminin receptor, SitC/MntC/saliva binding protein, Elastin binding protein (EbpS), EFB (FIB), SBI, autolysin, ClfA, SdrC, SdrG, SdrH, SasA, FnbA, FnbB, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig and MAP, Immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter, Aap and SsaA.
[0214] In the combinations described above, the alpha toxin may be genetically or chemically detoxified as described above and may be unconjugated or conjugated to polysaccharide as described below.
Polysaccharides
[0215] The immunogenic compositions of the invention preferably further comprise capsular polysaccharides including one or more of PIA (also known as PNAG) and/or S. Aureus Type V and/or type VIII capsular polysaccharide and/or S. Epidermidis Type I, and/or Type II and/or Type III capsular polysaccharide.
PIA (PNAG)
[0216] It is now clear that the various forms of staphylococcal surface polysaccharides identified as PS/A, PIA and SAA are the same chemical entity--PNAG (Maira-Litran et al., Vaccine 22; 872-879 (2004)). Therefore the term PIA or PNAG encompasses all these polysaccharides or oligosaccharides derived from them.
[0217] PIA is a polysaccharide intercellular adhesin and is composed of a polymer of β-(1→6)-linked glucosamine substituted with N-acetyl and O-succinyl constituents. This polysaccharide is present in both S. Aureus and S. Epidermidis and can be isolated from either source (Joyce et al. 2003, Carbohydrate Research 338; 903; Maira-Litran et al., 2002, Infect. Immune. 70; 4433). For example, PNAG may be isolated from S. Aureus strain MN8m (WO 04/43407).
[0218] PIA isolated from S. Epidermidis is a integral constituent of biofilm. It is responsible for mediating cell-cell adhesion and probably also functions to shield the growing colony from the host's immune response.
[0219] The polysaccharide previously known as poly-N-succinyl-β-(1→6)-glucosamine (PNSG) was recently shown not to have the expected structure since the identification of N-succinylation was incorrect (Maira-Litran et al., 2002, Infect. Immune. 70; 4433). Therefore the polysaccharide formally known as PNSG and now found to be PNAG is also encompassed by the term PIA.
[0220] PIA (or PNAG) may be of different sizes varying from over 400 kDa to between 75 and 400 kDa to between 10 and 75 kDa to oligosaccharides composed of up to 30 repeat units (of β-(1→6)-linked glucosamine substituted with N-acetyl and O-succinyl constituents). Any size of PIA polysaccharide or oligosaccharide may be use in an immunogenic composition of the invention, however a size of over 40 kDa is preferred. Sizing may be achieved by any method known in the art, for instance by microfluidisation, ultrasonic irradiation or by chemical cleavage (WO 03/53462, EP497524, EP497525).
[0221] Preferred size ranges of PIA (PNAG) are 40-400 kDa, 40-300 kDa, 50-350 kDa, 60-300 kDa, 50-250 kDa and 60-200 kDa.
[0222] PIA (PNAG) can have different degree of acetylation due to substitution on the amino groups by acetate. PIA produced in vitro is almost fully substituted on amino groups (95-100%). Alternatively, a deacetylated PIA (PNAG) can be used having less than 60%, preferably less than 50%, 40%, 30%, 20%, 10% acetylation. Use of a deacetylated PIA (PNAG) is preferred since non-acetylated epitopes of PNAG are efficient at mediating opsonic killing of Gram positive bacteria, preferably S. aureus and/or S. epidermidis. Most preferably, the PIA (PNAG) has a size between 40 kDa and 300 kDa and is deacetylated so that less than 60%, 50%, 40%, 30% or 20% of amino groups are acetylated.
[0223] The term deacetylated PNAG (dPNAG) refers to a PNAG polysaccharide or oligosaccharide in which less than 60%, 50%, 40%, 30%, 20% or 10% of the amino groups are acetylated.
[0224] In an embodiment, PNAG is a deacetylated to form dPNAG by chemically treating the native polysaccharide. For example, the native PNAG is treated with a basic solution such that the pH rises to above 10. For instance the PNAG is treated with 0.1-5M, 0.2-4M, 0.3-3M, 0.5-2M, 0.75-1.5M or 1M NaOH, KOH or NH4OH. Treatment is for at least 10 or 30 minutes, or 1, 2, 3, 4, 5, 10, 15 or 20 hours at a temperature of 20-100, 25-80, 30-60 or 30-50 or 35-45° C. dPNAG may be prepared as described in WO 04/43405.
[0225] The polysaccharide(s) included in the immunogenic composition of the invention are preferably conjugated to a carrier protein as described below or alternatively unconjugated.
Type 5 and Type 8 Polysaccharides from S. Aureus
[0226] Most strains of S. Aureus that cause infection in man contain either Type 5 or Type 8 polysaccharides. Approximately 60% of human strains are Type 8 and approximately 30% are Type 5. The structures of Type 5 and Type 8 capsular polysaccharide antigens are described in Moreau et al., Carbohydrate Res. 201; 285 (1990) and Fournier et al., Infect. Immune. 45; 87 (1984). Both have FucNAcp in their repeat unit as well as ManNAcA which can be used to introduce a sulfhydryl group. The structures were reported as:
[0227] Type 5
[0228] →4)-β-D-ManNAcA(3OAc)-(1→4)-α-L-FucNAc(1→- 3)-β-D-FucNAc-(1→
[0229] Type 8
[0230] →3)-β-D-ManNAcA(4OAc)-(1→3)-α-L-FucNAc(1→- 3)-β-D-FucNAc-(1→
[0231] Recently (Jones, Carbohydrate Research 340, 1097-1106 (2005)) NMR spectroscopy revised to structures to:
[0232] Type 5
[0233] →4)-β-D-ManNAcA-(1→4)-α-L-FucNAc(3OAc)-(1.fwdarw- .3)-β-D-FucNAc-(1→
[0234] Type 8
[0235] →3)-β-D-ManNAcA(4OAc)-(1→3)-α-L-FucNAc(1→- 3)-α-D-FucNAc(1→
[0236] Polysaccharides may be extracted from the appropriate strain of S. Aureus using method well known to the skilled man, for instance as described in U.S. Pat. No. 6,294,177. For example, ATCC 12902 is a Type 5 S. Aureus strain and ATCC 12605 is a Type 8 S. Aureus strain.
[0237] Polysaccharides are of native size or alternatively may be sized, for instance by microfluidisation, ultrasonic irradiation or by chemical treatment. The invention also covers oligosaccharides derived from the type 5 and 8 polysaccharides from S. Aureus.
[0238] The type 5 and 8 polysaccharides included in the immunogenic composition of the invention are preferably conjugated to a carrier protein as described below or are alternatively unconjugated.
[0239] The immunogenic compositions of the invention alternatively contain either type 5 or type 8 polysaccharide.
S. Aureus 336 Antigen
[0240] In an embodiment, the immunogenic composition of the invention comprises the S. Aureus 336 antigen described in U.S. Pat. No. 6,294,177.
[0241] The 336 antigen comprises β-linked hexosamine, contains no O-acetyl groups and specifically binds to antibodies to S. Aureus Type 336 deposited under ATCC 55804.
[0242] In an embodiment, the 336 antigen is a polysaccharide which is of native size or alternatively may be sized, for instance by microfluidisation, ultrasonic irradiation or by chemical treatment. The invention also covers oligosaccharides derived from the 336 antigen.
[0243] The 336 antigen, where included in the immunogenic composition of the invention, is preferably conjugated to a carrier protein as described below or are alternatively unconjugated.
Type I, II and III Polysaccharides from S. Epidermidis
[0244] Strains ATCC-31432, SE-360 and SE-10 of S. Epidermidis are characteristic of three different capsular types, I, II and III respectively (Ichiman and Yoshida 1981, J. Appl. Bacteriol. 51; 229). Capsular polysaccharides extracted from each serotype of S. Epidermidis constitute Type I, II and III polysaccharides. Polysaccharides may be extracted by serval methods including the method described in U.S. Pat. No. 4,197,290 or as described in Ichiman et al., 1991, J. Appl. Bacteriol. 71; 176.
[0245] In one embodiment of the invention, the immunogenic composition comprises type I and/or II and/or III polysaccharides or oligosaccharides from S. Epidermidis.
[0246] Polysaccharides are of native size or alternatively may be sized, for instance by microfluidisation, ultrasonic irradiation or chemical cleavage. The invention also covers oligosaccharides extracted from S. Epidermidis strains.
[0247] These polysaccharides are unconjugated or are preferably conjugated as described below.
Conjugation of Polysaccharides
[0248] Amongst the problems associated with the use of polysaccharides in vaccination, is the fact that polysaccharides per se are poor immunogens. Strategies, which have been designed to overcome this lack of immunogenicity, include the linking of the polysaccharide to large protein carriers, which provide bystander T-cell help. It is preferred that the polysaccharides utilized in the invention are linked to a protein carrier which provide bystander T-cell help. Examples of such carriers which may be conjugated to polysaccharide immunogens include the Diphtheria and Tetanus toxoids (DT, DT crm197 and TT respectively), Keyhole Limpet Hemocyanin (KLH), and the purified protein derivative of Tuberculin (PPD), Pseudomonas aeruginosa exoprotein A (rEPA), protein D from Haemophilus influenzae, pneumolysin or fragments of any of the above. Fragments suitable for use include fragments encompassing T-helper epitopes. In particular protein D fragment will preferably contain the N-terminal 1/3 of the protein. Protein D is an IgD-binding protein from Haemophilus influenzae (EP 0 594 610 B1) and is a potential immunogen.
[0249] In addition, staphylococcal proteins may be used as carrier protein in the polysaccharide conjugates of the invention. The staphylococcal proteins described below may be used as carrier protein; for example, laminin receptor, SitC/MntC/saliva binding protein, EbhA, EbhB, Elastin binding protein (EbpS), EFB (FIB), SBI, ClfA, SdrC, SdrG, SdrH, Lipase GehD, SasA, FnbA, FnbB, Cna, ClfB, FbpA, Npase, IsaA/PisA, SsaA, EPB, SSP-1, SSP-2, HBP, Vitronectin binding protein, fibrinogen binding protein, coagulase, Fig, MAP, Immunodominant ABC transporter, IsdA, IsdB, Mg2+ transporter, SitC, Ni ABC transporter alpha toxin (Hla), alpha toxin H35R mutant, RNA III activating protein (RAP), or fragments thereof.
[0250] A new carrier protein that would be particularly advantageous to use in the context of a staphylococcal vaccine is staphylococcal alpha toxic. The native form may be conjugated to a polysaccharide since the process of conjugation reduces toxicity. Preferably a genetically detoxified alpha toxin such as the His35Leu or His 35 Arg variants are used as carriers since residual toxicity is lower. Alternatively the alpha toxin is chemically detoxified by treatment with a cross-linking reagent, formaldehyde or glutaraldehyde. A genetically detoxified alpha toxin is optionally chemically detoxified, preferably by treatment with a cross-linking reagent, formaldehyde or glutaraldehyde to further reduce toxicity.
[0251] The polysaccharides may be linked to the carrier protein(s) by any known method (for example, by Likhite, U.S. Pat. No. 4,372,945 by Armor et al., U.S. Pat. No. 4,474,757, and Jennings et al., U.S. Pat. No. 4,356,170). Preferably, CDAP conjugation chemistry is carried out (see WO95/08348).
[0252] In CDAP, the cyanylating reagent 1-cyano-dimethylaminopyridinium tetrafluoroborate (CDAP) is preferably used for the synthesis of polysaccharide-protein conjugates. The cyanilation reaction can be performed under relatively mild conditions, which avoids hydrolysis of the alkaline sensitive polysaccharides. This synthesis allows direct coupling to a carrier protein.
[0253] The polysaccharide is solubilized in water or a saline solution. CDAP is dissolved in acetonitrile and added immediately to the polysaccharide solution. The CDAP reacts with the hydroxyl groups of the polysaccharide to form a cyanate ester. After the activation step, the carrier protein is added. Amino groups of lysine react with the activated polysaccharide to form an isourea covalent link. After the coupling reaction, a large excess of glycine is then added to quench residual activated functional groups. The product is then passed through a gel permeation column to remove unreacted carrier protein and residual reagents.
[0254] Conjugation preferably involves producing a direct linkage between the carrier protein and polysaccharide. Optionally a spacer (such as adipic dihydride (ADH)) may be introduced between the carrier protein and the polysaccharide.
Protection Against S. Aureus and S. Epidermidis
[0255] In a preferred embodiment of the invention the immunogenic composition provides an effective immune response against more than one strain of staphylococci, preferably against strains from both S. Aureus and S. Epidermidis. More preferably, a protective immune response is generated against type 5 and 8 serotypes of S. Aureus. More preferably, a protective immune response is generated against multiple strains of S. Epidermidis, for instance from strains of at least two of serotypes I, II and III of S. Epidermidis.
[0256] One use of the immunogenic composition of the invention is to prevent nosocomial infections by inoculating prior to hospital treatment. At this stage, it is difficult to accurately predict which staphylococcal strains the patient will be exposed to. It is therefore advantageous to inoculate with a vaccine that is capable of generating an effective immune response against various strains of staphylococci.
[0257] An effective immune response is defined as an immune response that gives significant protection in a mouse challenge model or opsonophagocytosis assay as described in the examples. Significant protection in a mouse challenge model, for instance that of example 5, is defined as an increase in the LD50 in comparison with carrier inoculated mice of at least 10%, 20%, 50%, 100% or 200%. Significant protection in a cotton rat challenge model, for instance that of example 8, is defined as a decrease in the mean observed Log CFU/nose of at least 10%, 20%, 50%, 70% or 90%. The presence of opsonizing antibodies is known to correlate with protection, therefore significant protection is indicated by a decrease in the bacterial count of at least 10%, 20%, 50%, 70% or 90% in an opsonophagocytosis assay, for instance that of Example 7.
[0258] Several of the proteins including immunodominant ABC transporter, RNA III activating protein, Laminin receptors, SitC, IsaA/PisA, SsaA, EbhA/EbhB, EbpS and Aap are well conserved between S. aureus and S. epidermidis and example 8 shows that IsaA, ClfA, IsdB, SdrG, HarA, FnbpA and Sbi can generate a cross-reactive immune response (for example cross-reactive between at least one S. aureus and at least one S. epidermidis strain). PIA is also well conserved between S. aureus and S. epidermidis and is capable of inducing a cross-protective immune response.
[0259] Therefore in a preferred embodiment, the immunogenic composition of the invention will comprise two, three or four of the above proteins, preferably further comprising PIA (PNAG).
Polynucleotide Vaccines
[0260] In a further aspect, the present invention relates to the use of the polynucleotides of FIG. 2 in the treatment, prevention or diagnosis of staphylococcal infection. Such polynucleotides include isolated polynucleotides comprising a nucleotide sequence encoding a polypeptide which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, to the amino acid sequence of FIG. 1, over the entire length of the sequence. In this regard, polypeptides which have at least 97% identity are highly preferred, whilst those with at least 98-99% identity are more highly preferred, and those with at least 99% identity are most highly preferred.
[0261] Further polynucleotides that find utility in the present invention include isolated polynucleotides comprising a nucleotide sequence that has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, to a nucleotide sequence encoding a protein of the invention over the entire coding region. In this regard, polynucleotides which have at least 97% identity are highly preferred, whilst those with at least 98-99% identity are more highly preferred, and those with at least 99% identity are most highly preferred.
[0262] Other polynucleotides include isolated polynucleotides comprising a nucleotide sequence which has at least 70% identity, preferably at least 80% identity, more preferably at least 90% identity, yet more preferably at least 95% identity, to the sequences of FIG. 1. In this regard, polynucleotides which have at least 97% identity are highly preferred, whilst those with at least 98-99% identity are more highly preferred, and those with at least 99% identity are most highly preferred. Said polynucleotide can be inserted in a suitable plasmid or recombinant microorganism vector and used for immunization (see for example Wolff et. al., Science 247:1465-1468 (1990); Con et. al., J. Exp. Med. 184:1555-1560 (1996); Doe et. al., Proc. Natl. Acad. Sci. 93:8578-8583 (1996)).
[0263] The present invention also provides a nucleic acid encoding the aforementioned proteins of the present invention and their use in medicine. In a preferred embodiment isolated polynucleotides according to the invention may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic, cDNA or synthetic) or RNA molecules. Additional coding or non-coding sequences may, but need not, be present within a polynucleotide of the present invention. In other related embodiments, the present invention provides polynucleotide variants having substantial identity to the sequences disclosed herein in FIG. 2; those comprising at least 70% sequence identity, preferably at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or higher, sequence identity compared to a polynucleotide sequence of this invention using the methods described herein, (e.g., BLAST analysis using standard parameters). In a related embodiment, the isolated polynucleotide of the invention will comprise a nucleotide sequence encoding a polypeptide that has at least 90%, preferably 95% and above, identity to the amino acid sequence of FIG. 1, over the entire length of a sequence of FIG. 1; or a nucleotide sequence complementary to said isolated polynucleotide.
[0264] The invention also contemplates the use of polynucleotides which are complementary to all the above described polynucleotides.
[0265] The invention also provides for the use of a fragment of a polynucleotide of the invention which when administered to a subject has the same immunogenic properties as a polynucleotide of FIG. 1.
[0266] The invention also provides for the use of a polynucleotide encoding an immunological fragment of a protein of FIG. 1 as hereinbefore defined. Also contemplated are the use of such fragments that have a level of immunogenic activity of at least about 50%, preferably at least about 70% and more preferably at least about 90% of the level of immunogenic activity of a polypeptide sequence encoded by a polynucleotide sequence set forth in FIG. 2.
[0267] Polypeptide fragments for use according to the invention preferably comprise at least about 5, 10, 15, 20, 25, 50, or 100 contiguous amino acids, or more, including all intermediate lengths, of a polypeptide composition set forth herein, such as those set forth above.
[0268] Polynucleotides for use in the invention may be obtained, using standard cloning and screening techniques, from a cDNA library derived from mRNA in cells of human preneoplastic or tumor tissue (lung for example), (for example Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)). Polynucleotides of the invention can also be obtained from natural sources such as genomic DNA libraries or can be synthesized using well-known and commercially available techniques.
[0269] There are several methods available and well known to those skilled in the art to obtain full-length cDNAs, or extend short cDNAs, for example those based on the method of Rapid Amplification of cDNA ends (RACE) (see, for example, Frohman et al., PNAS USA 85, 8998-9002, 1988). Recent modifications of the technique, exemplified by the Marathon® technology (Clontech Laboratories Inc.) for example, have significantly simplified the search for longer cDNAs. In the Marathon® technology, cDNAs have been prepared from mRNA extracted from a chosen tissue and an `adaptor` sequence ligated onto each end. Nucleic acid amplification (PCR) is then carried out to amplify the `missing` 5' end of the cDNA using a combination of gene specific and adaptor specific oligonucleotide primers. The PCR reaction is then repeated using `nested` primers, that is, primers designed to anneal within the amplified product (typically an adaptor specific primer that anneals further 3' in the adaptor sequence and a gene specific primer that anneals further 5' in the known gene sequence). The products of this reaction can then be analyzed by DNA sequencing and a full-length cDNA constructed either by joining the product directly to the existing cDNA to give a complete sequence, or carrying out a separate full-length PCR using the new sequence information for the design of the 5' primer.
[0270] Vectors comprising such DNA, hosts transformed thereby and the truncated or hybrid proteins themselves, expressed as described herein below all form part of the invention.
[0271] The expression system may also be a recombinant live microorganism, such as a virus or bacterium. The gene of interest can be inserted into the genome of a live recombinant virus or bacterium. Inoculation and in vivo infection with this live vector will lead to in vivo expression of the antigen and induction of immune responses.
[0272] Therefore, in certain embodiments, polynucleotides encoding immunogenic polypeptides for use according to the present invention are introduced into suitable mammalian host cells for expression using any of a number of known viral-based systems. In one illustrative embodiment, retroviruses provide a convenient and effective platform for gene delivery systems. A selected nucleotide sequence encoding a polypeptide for use in the present invention can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to a subject. A number of illustrative retroviral systems have been described (e.g., U.S. Pat. No. 5,219,740; Miller and Rosman (1989) BioTechniques 7:980-990; Miller, A. D. (1990) Human Gene Therapy 1:5-14; Scarpa et al. (1991) Virology 180:849-852; Burns et al. (1993) Proc. Natl. Acad. Sci. USA 90:8033-8037; and Boris-Lawrie and Temin (1993) Cur. Opin. Genet. Develop. 3:102-109.
[0273] In addition, a number of illustrative adenovirus-based systems have also been described. Unlike retroviruses which integrate into the host genome, adenoviruses persist extrachromosomally thus minimizing the risks associated with insertional mutagenesis (Haj-Ahmad and Graham (1986) J. Virol. 57:267-274; Bett et al. (1993) J. Virol. 67:5911-5921; Mittereder et al. (1994) Human Gene Therapy 5:717-729; Seth et al. (1994) J. Virol. 68:933-940; Barr et al. (1994) Gene Therapy 1:51-58; Berkner, K. L. (1988) BioTechniques 6:616-629; and Rich et al. (1993) Human Gene Therapy 4:461-476).
[0274] Various adeno-associated virus (AAV) vector systems have also been developed for polynucleotide delivery. AAV vectors can be readily constructed using techniques well known in the art. See, e.g., U.S. Pat. Nos. 5,173,414 and 5,139,941; International Publication Nos. WO 92/01070 and WO 93/03769; Lebkowski et al. (1988) Molec. Cell. Biol. 8:3988-3996; Vincent et al. (1990) Vaccines 90 (Cold Spring Harbor Laboratory Press); Carter, B. J. (1992) Current Opinion in Biotechnology 3:533-539; Muzyczka, N. (1992) Current Topics in Microbiol. and Immunol. 158:97-129; Kotin, R. M. (1994) Human Gene Therapy 5:793-801; Shelling and Smith (1994) Gene Therapy 1:165-169; and Zhou et al. (1994) J. Exp. Med. 179:1867-1875.
[0275] Additional viral vectors useful for delivering the nucleic acid molecules encoding polypeptides for use in the present invention by gene transfer include those derived from the pox family of viruses, such as vaccinia virus and avian poxvirus. By way of example, vaccinia virus recombinants expressing the molecules of interest can be constructed as follows. The DNA encoding a polypeptide is first inserted into an appropriate vector so that it is adjacent to a vaccinia promoter and flanking vaccinia DNA sequences, such as the sequence encoding thymidine kinase (TK). This vector is then used to transfect cells which are simultaneously infected with vaccinia. Homologous recombination serves to insert the vaccinia promoter plus the gene encoding the polypeptide of interest into the viral genome. The resulting TK.sup.(-) recombinant can be selected by culturing the cells in the presence of 5-bromodeoxyuridine and picking viral plaques resistant thereto.
[0276] A vaccinia-based infection/transfection system can be conveniently used to provide for inducible, transient expression or co-expression of one or more polypeptides described herein in host cells of an organism. In this particular system, cells are first infected in vitro with a vaccinia virus recombinant that encodes the bacteriophage T7 RNA polymerase. This polymerase displays exquisite specificity in that it only transcribes templates bearing T7 promoters. Following infection, cells are transfected with the polynucleotide or polynucleotides of interest, driven by a T7 promoter. The polymerase expressed in the cytoplasm from the vaccinia virus recombinant transcribes the transfected DNA into RNA which is then translated into polypeptide by the host translational machinery. The method provides for high level, transient, cytoplasmic production of large quantities of RNA and its translation products. See, e.g., Elroy-Stein and Moss, Proc. Natl. Acad. Sci. USA (1990) 87:6743-6747; Fuerst et al., Proc. Natl. Acad. Sci. USA (1986) 83:8122-8126.
[0277] Alternatively, avipoxviruses, such as the fowlpox and canarypox viruses, can also be used to deliver the coding sequences of interest. Recombinant avipox viruses, expressing immunogens from mammalian pathogens, are known to confer protective immunity when administered to non-avian species. The use of an Avipox vector is particularly desirable in human and other mammalian species since members of the Avipox genus can only productively replicate in susceptible avian species and therefore are not infective in mammalian cells. Methods for producing recombinant Avipoxviruses are known in the art and employ genetic recombination, as described above with respect to the production of vaccinia viruses. See, e.g., WO 91/12882; WO 89/03429; and WO 92/03545.
[0278] Any of a number of alphavirus vectors can also be used for delivery of polynucleotide compositions for use in the present invention, such as those vectors described in U.S. Pat. Nos. 5,843,723; 6,015,686; 6,008,035 and 6,015,694. Certain vectors based on Venezuelan Equine Encephalitis (VEE) can also be used, illustrative examples of which can be found in U.S. Pat. Nos. 5,505,947 and 5,643,576.
[0279] Moreover, molecular conjugate vectors, such as the adenovirus chimeric vectors described in Michael et al., J. Biol. Them. (1993) 268:6866-6869 and Wagner et al., Proc. Natl. Acad. Sci. USA (1992) 89:6099-6103, can also be used for gene delivery under the invention.
[0280] Additional illustrative information on these and other known viral-based delivery systems can be found, for example, in Fisher-Hoch et al., Proc. Natl. Acad. Sci. USA 86:317-321, 1989; Flexner et al., Ann. N.Y. Acad. Sci. 569:86-103, 1989; Flexner et al., Vaccine 8:17-21, 1990; U.S. Pat. Nos. 4,603,112, 4,769,330, and 5,017,487; WO 89/01973; U.S. Pat. No. 4,777,127; GB 2,200,651; EP 0,345,242; WO 91/02805; Berkner, BioTechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431-434, 1991; Kolls et al., Proc. Natl. Acad. Sci. USA 91:215-219, 1994; Kass-Eisler et al., Proc. Natl. Acad. Sci. USA 90:11498-11502, 1993; Guzman et al., Circulation 88:2838-2848, 1993; and Guzman et al., Cir. Res. 73:1202-1207, 1993.
[0281] The recombinant live microorganisms described above can be virulent, or attenuated in various ways in order to obtain live vaccines. Such live vaccines also form part of the invention.
[0282] In certain embodiments, a polynucleotide may be integrated into the genome of a target cell. This integration may be in the specific location and orientation via homologous recombination (gene replacement) or it may be integrated in a random, non-specific location (gene augmentation). In yet further embodiments, the polynucleotide may be stably maintained in the cell as a separate, episomal segment of DNA. Such polynucleotide segments or "episomes" encode sequences sufficient to permit maintenance and replication independent of or in synchronization with the host cell cycle. The manner in which the expression construct is delivered to a cell and where in the cell the polynucleotide remains is dependent on the type of expression construct employed.
[0283] In another embodiment of the invention, a polynucleotide is administered/delivered as "naked" DNA, for example as described in Ulmer et al., Science 259:1745-1749, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.
[0284] In still another embodiment, a composition of the present invention can be delivered via a particle bombardment approach, many of which have been described. In one illustrative example, gas-driven particle acceleration can be achieved with devices such as those manufactured by Powderject Pharmaceuticals PLC (Oxford, UK) and Powderject Vaccines Inc. (Madison, Wis.), some examples of which are described in U.S. Pat. Nos. 5,846,796; 6,010,478; 5,865,796; 5,584,807; and EP Patent No. 0500 799. This approach offers a needle-free delivery approach wherein a dry powder formulation of microscopic particles, such as polynucleotide or polypeptide particles, are accelerated to high speed within a helium gas jet generated by a hand held device, propelling the particles into a target tissue of interest.
[0285] In a related embodiment, other devices and methods that may be useful for gas-driven needle-less injection of compositions of the present invention include those provided by Bioject, Inc. (Portland, Oreg.), some examples of which are described in U.S. Pat. Nos. 4,790,824; 5,064,413; 5,312,335; 5,383,851; 5,399,163; 5,520,639 and 5,993,412.
Vaccines
[0286] In a preferred embodiment, the immunogenic composition of the invention is mixed with a pharmaceutically acceptable excipient, more preferably with an adjuvant to form a vaccine.
[0287] The vaccines of the present invention are preferably adjuvanted. Suitable adjuvants include an aluminum salt such as aluminum hydroxide gel (alum) or aluminum phosphate, but may also be a salt of calcium, magnesium, iron or zinc, or may be an insoluble suspension of acylated tyrosine, or acylated sugars, cationically or anionically derivatized polysaccharides, or polyphosphazenes.
[0288] It is preferred that the adjuvant be selected to be a preferential inducer of either a TH1 or a TH2 type of response. High levels of Th1-type cytokines tend to favor the induction of cell mediated immune responses to a given antigen, whilst high levels of Th2-type cytokines tend to favor the induction of humoral immune responses to the antigen.
[0289] It is important to remember that the distinction of Th1 and Th2-type immune response is not absolute. In reality an individual will support an immune response which is described as being predominantly Th1 or predominantly Th2. However, it is often convenient to consider the families of cytokines in terms of that described in murine CD4+ve T cell clones by Mosmann and Coffman (Mosmann, T. R. and Coffman, R. L. (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology, 7, p145-173). Traditionally, Th1-type responses are associated with the production of the INF-γ and IL-2 cytokines by T-lymphocytes. Other cytokines often directly associated with the induction of Th1-type immune responses are not produced by T-cells, such as IL-12. In contrast, Th2-type responses are associated with the secretion of Il-4, IL-5, IL-6, IL-10. Suitable adjuvant systems which promote a predominantly Th1 response include: Monophosphoryl lipid A or a derivative thereof, particularly 3-de-O-acylated monophosphoryl lipid A (3D-MPL) (for its preparation see GB 2220211 A); and a combination of monophosphoryl lipid A, preferably 3-de-O-acylated monophosphoryl lipid A, together with either an aluminum salt (for instance aluminum phosphate or aluminum hydroxide) or an oil-in-water emulsion. In such combinations, antigen and 3D-MPL are contained in the same particulate structures, allowing for more efficient delivery of antigenic and immunostimulatory signals. Studies have shown that 3D-MPL is able to further enhance the immunogenicity of an alum-adsorbed antigen (Thoelen et al. Vaccine (1998) 16:708-14; EP 689454-B1).
[0290] An enhanced system involves the combination of a monophosphoryl lipid A and a saponin derivative, particularly the combination of QS21 and 3D-MPL as disclosed in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol as disclosed in WO 96/33739. A particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil in water emulsion is described in WO 95/17210, and is a preferred formulation. Preferably the vaccine additionally comprises a saponin, more preferably QS21. The formulation may also comprise an oil in water emulsion and tocopherol (WO 95/17210). The present invention also provides a method for producing a vaccine formulation comprising mixing a protein of the present invention together with a pharmaceutically acceptable excipient, such as 3D-MPL. Unmethylated CpG containing oligonucleotides (WO 96/02555) are also preferential inducers of a TH1 response and are suitable for use in the present invention.
[0291] Preferred compositions of the invention are those forming a liposome structure. Compositions where the sterol/immunologically active saponin fraction forms an ISCOM structure also form an aspect of the invention.
[0292] The ratio of QS21: sterol will typically be in the order of 1:100 to 1:1 weight to weight. Preferably excess sterol is present, the ratio of QS21:sterol being at least 1:2 w/w. Typically for human administration QS21 and sterol will be present in a vaccine in the range of about 1 μg to about 100 μg, preferably about 10 μg to about 50 μg per dose.
[0293] The liposomes preferably contain a neutral lipid, for example phosphatidylcholine, which is preferably non-crystalline at room temperature, for example egg yolk phosphatidylcholine, dioleoyl phosphatidylcholine or dilauryl phosphatidylcholine. The liposomes may also contain a charged lipid which increases the stability of the lipsome-QS21 structure for liposomes composed of saturated lipids. In these cases the amount of charged lipid is preferably 1-20% w/w, most preferably 5-10%. The ratio of sterol to phospholipid is 1-50% (mol/mol), most preferably 20-25%.
[0294] Preferably the compositions of the invention contain MPL (3-deacylated mono-phosphoryl lipid A, also known as 3D-MPL). 3D-MPL is known from GB 2 220 211 (Ribi) as a mixture of 3 types of De-O-acylated monophosphoryl lipid A with 4, 5 or 6 acylated chains and is manufactured by Ribi Immunochem, Montana. A preferred form is disclosed in International Patent Application 92/116556.
[0295] Suitable compositions of the invention are those wherein liposomes are initially prepared without MPL, and MPL is then added, preferably as 100 nm particles. The MPL is therefore not contained within the vesicle membrane (known as MPL out). Compositions where the MPL is contained within the vesicle membrane (known as MPL in) also form an aspect of the invention. The antigen can be contained within the vesicle membrane or contained outside the vesicle membrane. Preferably soluble antigens are outside and hydrophobic or lipidated antigens are either contained inside or outside the membrane.
[0296] The vaccine preparations of the present invention may be used to protect or treat a mammal susceptible to infection, by means of administering said vaccine via systemic or mucosal route. These administrations may include injection via the intramuscular, intraperitoneal, intradermal or subcutaneous routes; or via mucosal administration to the oral/alimentary, respiratory, genitourinary tracts. Intranasal administration of vaccines for the treatment of pneumonia or otitis media is preferred (as nasopharyngeal carriage of pneumococci can be more effectively prevented, thus attenuating infection at its earliest stage). Although the vaccine of the invention may be administered as a single dose, components thereof may also be co-administered together at the same time or at different times (for instance pneumococcal polysaccharides could be administered separately, at the same time or 1-2 weeks after the administration of any bacterial protein component of the vaccine for optimal coordination of the immune responses with respect to each other). For co-administration, the optional Th1 adjuvant may be present in any or all of the different administrations, however it is preferred if it is present in combination with the bacterial protein component of the vaccine. In addition to a single route of administration, 2 different routes of administration may be used. For example, polysaccharides may be administered IM (or ID) and bacterial proteins may be administered IN (or ID). In addition, the vaccines of the invention may be administered IM for priming doses and IN for booster doses.
[0297] The amount of conjugate antigen in each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccines. Such amount will vary depending upon which specific immunogen is employed and how it is presented. Generally, it is expected that each dose will comprise 0.1-100 μg of polysaccharide, preferably 0.1-50 μg for polysaccharide conjugates, preferably 0.1-10 μg, more preferably 1-10 μg, of which 1 to 5 μg is a more preferable range.
[0298] The content of protein antigens in the vaccine will typically be in the range 1-100 μg, preferably 5-50 μg, most typically in the range 5-25 μg. Following an initial vaccination, subjects may receive one or several booster immunizations adequately spaced.
[0299] Vaccine preparation is generally described in Vaccine Design ("The subunit and adjuvant approach" (eds Powell M. F. & Newman M. J.) (1995) Plenum Press New York). Encapsulation within liposomes is described by Fullerton, U.S. Pat. No. 4,235,877.
[0300] The vaccines of the present invention may be stored in solution or lyophilized. Preferably the solution is lyophilized in the presence of a sugar such as sucrose, trehalose or lactose. It is still further preferable that they are lyophilized and extemporaneously reconstituted prior to use. Lyophilizing may result in a more stable composition (vaccine) and may possibly lead to higher antibody titers in the presence of 3D-MPL and in the absence of an aluminum based adjuvant.
Antibodies and Passive Immunization
[0301] Another aspect of the invention is a method of preparing an immune globulin for use in prevention or treatment of staphylococcal infection comprising the steps of immunizing a recipient with the vaccine of the invention and isolating immune globulin from the recipient. An immune globulin prepared by this method is a further aspect of the invention. A pharmaceutical composition comprising the immune globulin of the invention and a pharmaceutically acceptable carrier is a further aspect of the invention which could be used in the manufacture of a medicament for the treatment or prevention of staphylococcal disease. A method for treatment or prevention of staphylococcal infection comprising a step of administering to a patient an effective amount of the pharmaceutical preparation of the invention is a further aspect of the invention.
[0302] Inocula for polyclonal antibody production are typically prepared by dispersing the antigenic composition in a physiologically tolerable diluent such as saline or other adjuvants suitable for human use to form an aqueous composition. An immunostimulatory amount of inoculum is administered to a mammal and the inoculated mammal is then maintained for a time sufficient for the antigenic composition to induce protective antibodies.
[0303] The antibodies can be isolated to the extent desired by well known techniques such as affinity chromatography (Harlow and Lane Antibodies; a laboratory manual 1988).
[0304] Antibodies can include antiserum preparations from a variety of commonly used animals e.g., goats, primates, donkeys, swine, horses, guinea pigs, rats or man. The animals are bled and serum recovered.
[0305] An immune globulin produced in accordance with the present invention can include whole antibodies, antibody fragments or subfragments. Antibodies can be whole immunoglobulins of any class e.g., IgG, IgM, IgA, IgD or IgE, chimeric antibodies or hybrid antibodies with dual specificity to two or more antigens of the invention. They may also be fragments e.g., F(ab')2, Fab', Fab, Fv and the like including hybrid fragments. An immune globulin also includes natural, synthetic or genetically engineered proteins that act like an antibody by binding to specific antigens to form a complex.
[0306] A vaccine of the present invention can be administered to a recipient who then acts as a source of immune globulin, produced in response to challenge from the specific vaccine. A subject thus treated would donate plasma from which hyperimmune globulin would be obtained via conventional plasma fractionation methodology. The hyperimmune globulin would be administered to another subject in order to impart resistance against or treat staphylococcal infection. Hyperimmune globulins of the invention are particularly useful for treatment or prevention of staphylococcal disease in infants, immune compromised individuals or where treatment is required and there is no time for the individual to produce antibodies in response to vaccination.
[0307] An additional aspect of the invention is a pharmaceutical composition comprising two of more monoclonal antibodies (or fragments thereof; preferably human or humanized) reactive against at least two constituents of the immunogenic composition of the invention, which could be used to treat or prevent infection by Gram positive bacteria, preferably staphylococci, more preferably S. Aureus or S. Epidermidis.
[0308] Such pharmaceutical compositions comprise monoclonal antibodies that can be whole immunoglobulins of any class e.g. IgG, IgM, IgA, IgD or IgE, chimeric antibodies or hybrid antibodies with specificity to two or more antigens of the invention. They may also be fragments e.g., F(ab')2, Fab', Fab, Fv and the like including hybrid fragments.
[0309] Methods of making monoclonal antibodies are well known in the art and can include the fusion of splenocytes with myeloma cells (Kohler and Milstein 1975 Nature 256; 495; Antibodies--a laboratory manual Harlow and Lane 1988). Alternatively, monoclonal Fv fragments can be obtained by screening a suitable phage display library (Vaughan T J et al., 1998 Nature Biotechnology 16; 535). Monoclonal antibodies may be humanized or part humanized by known methods.
Methods
[0310] The invention also encompasses method of making the immunogenic compositions and vaccines of the invention.
[0311] A preferred process of the invention, is a method to make a vaccine comprising the steps of mixing antigens to make the immunogenic composition of the invention and adding a pharmaceutically acceptable excipient.
Methods of Treatment
[0312] The invention also encompasses method of treatment or staphylococcal infection, particularly hospital acquired nosocomial infections.
[0313] This immunogenic composition or vaccine of the invention is particularly advantageous to use in cases of elective surgery. Such patients will know the date of surgery in advance and could be inoculated in advance. Since it is not known whether the patient will be exposed to S. Aureus or S. Epidermidis infection, it is preferred to inoculate with a vaccine of the invention that protects against both, as described above. Preferably adults over 16 awaiting elective surgery are treated with the immunogenic compositions and vaccines of the invention.
[0314] It is also advantageous to inoculate health care workers with the vaccine of the invention.
[0315] The vaccine preparations of the present invention may be used to protect or treat a mammal susceptible to infection, by means of administering said vaccine via systemic or mucosal route. These administrations may include injection via the intramuscular, intraperitoneal, intradermal or subcutaneous routes; or via mucosal administration to the oral/alimentary, respiratory, genitourinary tracts.
[0316] The amount of antigen in each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccines. Such amount will vary depending upon which specific immunogen is employed and how it is presented. The protein content of the vaccine will typically be in the range 1-100 μg, preferably 5-50 μg, most typically in the range 10-25 μg. Generally, it is expected that each dose will comprise 0.1-100 μg of polysaccharide where present, preferably 0.1-50 μg, preferably 0.1-10 μg, of which 1 to 5 μg is the most preferable range. An optimal amount for a particular vaccine can be ascertained by standard studies involving observation of appropriate immune responses in subjects. Following an initial vaccination, subjects may receive one or several booster immunizations adequately spaced.
[0317] Although the vaccines of the present invention may be administered by any route, administration of the described vaccines into the skin (ID) forms one embodiment of the present invention. Human skin comprises an outer "horny" cuticle, called the stratum corneum, which overlays the epidermis. Underneath this epidermis is a layer called the dermis, which in turn overlays the subcutaneous tissue. Researchers have shown that injection of a vaccine into the skin, and in particular the dermis, stimulates an immune response, which may also be associated with a number of additional advantages. Intradermal vaccination with the vaccines described herein forms a preferred feature of the present invention.
[0318] The conventional technique of intradermal injection, the "mantoux procedure", comprises steps of cleaning the skin, and then stretching with one hand, and with the bevel of a narrow gauge needle (26-31 gauge) facing upwards the needle is inserted at an angle of between 10-15°. Once the bevel of the needle is inserted, the barrel of the needle is lowered and further advanced whilst providing a slight pressure to elevate it under the skin. The liquid is then injected very slowly thereby forming a bleb or bump on the skin surface, followed by slow withdrawal of the needle.
[0319] More recently, devices that are specifically designed to administer liquid agents into or across the skin have been described, for example the devices described in WO 99/34850 and EP 1092444, also the jet injection devices described for example in WO 01/13977; U.S. Pat. No. 5,480,381, U.S. Pat. No. 5,599,302, U.S. Pat. No. 5,334,144, U.S. Pat. No. 5,993,412, U.S. Pat. No. 5,649,912, U.S. Pat. No. 5,569,189, U.S. Pat. No. 5,704,911, U.S. Pat. No. 5,383,851, U.S. Pat. No. 5,893,397, U.S. Pat. No. 5,466,220, U.S. Pat. No. 5,339,163, U.S. Pat. No. 5,312,335, U.S. Pat. No. 5,503,627, U.S. Pat. No. 5,064,413, U.S. Pat. No. 5,520,639, U.S. Pat. No. 4,596,556, U.S. Pat. No. 4,790,824, U.S. Pat. No. 4,941,880, U.S. Pat. No. 4,940,460, WO 97/37705 and WO 97/13537. Alternative methods of intradermal administration of the vaccine preparations may include conventional syringes and needles, or devices designed for ballistic delivery of solid vaccines (WO 99/27961), or transdermal patches (WO 97/48440; WO 98/28037); or applied to the surface of the skin (transdermal or transcutaneous delivery WO 98/20734; WO 98/28037).
[0320] When the vaccines of the present invention are to be administered to the skin, or more specifically into the dermis, the vaccine is in a low liquid volume, particularly a volume of between about 0.05 ml and 0.2 ml.
[0321] The content of antigens in the skin or intradermal vaccines of the present invention may be similar to conventional doses as found in intramuscular vaccines (see above). However, it is a feature of skin or intradermal vaccines that the formulations may be "low dose". Accordingly the protein antigens in "low dose" vaccines are preferably present in as little as 0.1 to 10 μg, preferably 0.1 to 5 μg per dose; and the polysaccharide (preferably conjugated) antigens may be present in the range of 0.01-1 μg, and preferably between 0.01 to 0.5 μg of polysaccharide per dose.
[0322] As used herein, the term "intradermal delivery" means delivery of the vaccine to the region of the dermis in the skin. However, the vaccine will not necessarily be located exclusively in the dermis. The dermis is the layer in the skin located between about 1.0 and about 2.0 mm from the surface in human skin, but there is a certain amount of variation between individuals and in different parts of the body. In general, it can be expected to reach the dermis by going 1.5 mm below the surface of the skin. The dermis is located between the stratum corneum and the epidermis at the surface and the subcutaneous layer below. Depending on the mode of delivery, the vaccine may ultimately be located solely or primarily within the dermis, or it may ultimately be distributed within the epidermis and the dermis.
[0323] A preferred embodiment of the invention is a method of preventing or treating staphylococcal infection or disease comprising the step of administering the immunogenic composition or vaccine of the invention to a patient in need thereof.
[0324] In a preferred embodiment, the patient is awaiting elective surgery.
[0325] A further preferred embodiment of the invention is a use of the immunogenic composition of the invention in the manufacture of a vaccine for treatment or prevention of staphylococcal infection or disease, preferably post-surgery staphylococcal infection.
[0326] The term `staphylococcal infection` encompasses infection caused by S. Aureus and/or S. Epidermidis and other staphylococcal strains capable of causing infection in a mammalian, preferably human host.
[0327] The terms "comprising", "comprise" and "comprises" herein are intended by the inventors to be optionally substitutable with the terms "consisting of", "consist of" and "consists of", respectively, in every instance.
[0328] All references or patent applications cited within this patent specification are incorporated by reference herein.
[0329] In order that this invention may be better understood, the following examples are set forth. These examples are for purposes of illustration only, and are not to be construed as limiting the scope of the invention in any manner.
EXAMPLES
Example 1
Construction of Plasmid to Express Recombiant Proteins
A: Cloning
[0330] Appropriate restriction sites engineered into oligonucleotides specific for the staphylococcal gene permitted directional cloning of the PCR product into the E. coli expression plasmid pET24d or pQE-30 such that a protein could be expressed as a fusion protein containing a (His)6 affinity chromatography tag at the N- or C-terminus.
[0331] The primers used were (SEQ ID NOS: 120-151 respectively):
TABLE-US-00009 Alpha toxin- 5'-CGCGGATCCGCAGATTCTGATATTAATATTAAAAC-3' and 5'CCCAAGCTTTTAATTTGTCATTTCTTCTTTTTC-3' EbpS- 5'-CGCGGATCCGCTGGGTCTAATAATTTTAAAGATG-3' and 5'CCCAAGCTTTTATGGAATAACGATTTGTTG-3' ClfA- 5'-CGCGGATCCAGTGAAAATAGTGTTACGCAATC-3' and 5'CCCAAGCTTTTACTCTGGAATTGGTTCAATTTC-3' FnbpA- 5'-CGCGGATCCACACAAACAACTGCAACTAACG-3' and 5'CCCAAGCTTTTATGCTTTGTGATTCTTTTTCAAAC3' Sbi- 5'-CGCGGATCCAACACGCAACAAACTTC-3' and 5'GGAACTGCAGTTATTTCCAGAATGATAATAAATTAC-3' SdrC- 5'-CGCGGATCCGCAGAACATACGAATGGAG-3' and 5'CCCAAGCTTTTATGTTTCTTCTTCGTAGTAGC-3' SdrG- 5'-CGCGGATCCGAGGAGAATTCAGTACAAG-3' and 5'CCCAAGCTTTTATTCGTCATCATAGTATCCG-3' Ebh- 5'-AAAAGTACTCACCACCACCACCACC-3' and 5'AAAAGTACTCACTTGATTCATCGCTTCAG-3' Aaa- 5'-GCGCGCCATGGCACAAGCTTCTACACAACATAC-3' and 5'GCGCGCTCGAGATGGATGAATGCATAGCTAGA-3' IsaA- 5'-GCATCCATGGCACCATCACCATCACCACGAAGTAAACGT TGATCAAGC-3' and 5'-AGCACTCGAGTTAGAATCCCCAAGCACCTAAACC-3' HarA- 5'-GCACCCATGGCAGAAAATACAAATACTTC-3' and 5'TTTTCTCGAGCATTTTAGATTGACTAAGTTG-3' Autolysin glucosaminidase- 5'-CAAGTCCCATGGCTGAGACGACACAAGATCAAC-3' and 5'-CAGTCTCGAGTTTTACAGCTGTTTTTGGTTG-3' Autolysin amidase- 5'-AGCTCATATGGCTTATACTGTTACTAAACC-3' and 5'GCGCCTCGAGTTTATATTGTGGGATGTCG-3' IsdA- 5'-CAAGTCCCATGGCAACAGAAGCTACGAACGCAAC-3' and 5'ACCAGTCTCGAGTAATTCTTTAGCTTTAGAGCTTG-3' IsdB- 5'-TATTCTCGAGGCTTTGAGTGTGTCCATCATTTG-3' and 5'GAAGCCATGGCAGCAGCTGAAGAAACAGGTGG-3' MRPII- 5'-GATTACACCATGGTTAAACCTCAAGCGAAA-3' and 5'AGGTGTCTCGAGTGCGATTGTAGCTTCATT-3'
[0332] The PCR products were first introduced into the pGEM-T cloning vector (Novagen) using Top10 bacterial cells, according to the manufacturer's instructions. This intermediate construct was made to facilitate further cloning into an expression vector. Transformants containing the DNA insert were selected by restriction enzyme analysis. Following digestion, a ˜20 μl aliquot of the reaction was analyzed by agarose gel electrophoresis (0.8% agarose in a Tris-acetate-EDTA (TAE) buffer). DNA fragments were visualized by UV illumination after gel electrophoresis and ethidium bromide staining A DNA molecular size standard (1 Kb ladder, Life Technologies) was electrophoresed in parallel with the test samples and was used to estimate the size of the DNA fragments. Plasmid purified from selected transformants for each cloning was then sequentially digested to completion with appropriate restriction enzymes as recommended by the manufacturer (Life Technologies). The digested DNA fragment was then purified using silica gel-based spin columns prior to ligation with the pET24d or pQE-30 plasmid. Cloning of Ebh (H2 fragment), AaA, IsdA, IsdB, HarA, Atl-amidase, Atl-glucosamine, MRP, IsaA was carried out using the pET24d plasmid and cloning of ClfA, SdrC, SdrE, FnbpA, SdrG/Fbe, alpha toxin and Sbi were carried out using the pQE-30 plasmid.
B: Production of Expression Vector
[0333] To prepare the expression plasmid pET24d or pQE-30 for ligation, it was similarly digested to completion with appropriate restriction enzymes. An approximately 5-fold molar excess of the digested fragments to the prepared vector was used to program the ligation reaction. A standard ˜20 μl ligation reaction (˜16° C., ˜16 hours), using methods well known in the art, was performed using T4 DNA ligase (˜2.0 units/reaction, Life Technologies). An aliquot of the ligation (˜5 μl) was used to transform M15(pREP4) or BT21::DE3 electro-competent cells according to methods well known in the art. Following a ˜2-3 hour outgrowth period at 37° C. in ˜1.0 ml of LB broth, transformed cells were plated on LB agar plates containing ampicillin (100 μg/ml) and/or kanamycin (30 μg/ml). Antibiotics were included in the selection. Plates were incubated overnight at 37° C. for ˜16 hours. Individual ApR/KanR colonies were picked with sterile toothpicks and used to "patch" inoculate fresh LB ApR/KanR plates as well as a ˜1.0 ml LB Ap/Kan broth culture. Both the patch plates and the broth culture were incubated overnight at 37° C. in either a standard incubator (plates) or a shaking water bath. A whole cell-based PCR analysis was employed to verify that transformants contained the DNA insert. Here, the ˜1.0 ml overnight LB Ap/Kan broth culture was transferred to a 1.5 ml polypropylene tube and the cells collected by centrifugation in a Beckmann microcentrifuge (˜3 min., room temperature, ˜12,000× g). The cell pellet was suspended in ˜200 μl of sterile water and a ˜10 μl aliquot used to program a ˜50 μl final volume PCR reaction containing both forward and reverse amplification primers. The initial 95° C. denaturation step was increased to 3 minutes to ensure thermal disruption of the bacterial cells and liberation of plasmid DNA. An ABI Model 9700 thermal cycler and a 32 cycle, three-step thermal amplification profile, i.e. 95° C., 45 sec; 55-58° C., 45 sec, 72° C., 1 min., were used to amplify the BASB203 fragment from the lysed transformant samples. Following thermal amplification, a ˜20 μl aliquot of the reaction was analyzed by agarose gel electrophoresis (0.8% agarose in a Tris-acetate-EDTA (TAE) buffer). DNA fragments were visualized by UV illumination after gel electrophoresis and ethidium bromide staining A DNA molecular size standard (1 Kb ladder, Life Technologies) was electrophoresed in parallel with the test samples and was used to estimate the size of the PCR products. Transformants that produced the expected size PCR product were identified as strains containing a protein expression construct. Expression plasmid containing strains were then analyzed for the inducible expression of recombinant protein.
C: Expression Analysis of PCR-Positive Transformants
[0334] An aliquot of the overnight seed culture (˜1.0 ml) was inoculated into a 125 ml Erlenmeyer flask containing ˜25 ml of LB Ap/Kan broth and was grown at 37° C. with shaking (˜250 rpm) until the culture turbidity reached O.D.600 of ˜0.5, i.e. mid-log phase (usually about 1.5-2.0 hours). At this time approximately half of the culture (˜12.5 ml) was transferred to a second 125 ml flask and expression of recombinant protein induced by the addition of IPTG (1.0M stock prepared in sterile water, Sigma) to a final concentration of 1.0 mM. Incubation of both the IPTG-induced and non-induced cultures continued for an additional ˜4 hours at 37° C. with shaking Samples (˜1.0 ml) of both induced and non-induced cultures were removed after the induction period and the cells collected by centrifugation in a microcentrifuge at room temperature for ˜3 minutes. Individual cell pellets were suspended in ˜50 μl of sterile water, then mixed with an equal volume of 2× Laemelli SDS-PAGE sample buffer containing 2-mercaptoethanol, and placed in boiling water bath for ˜3 min to denature protein. Equal volumes (˜15 μl) of both the crude IPTG-induced and the non-induced cell lysates were loaded onto duplicate 12% Tris/glycine polyacrylamide gel (1 mm thick Mini-gels, Novex). The induced and non-induced lysate samples were electrophoresed together with prestained molecular weight markers (SeeBlue, Novex) under conventional conditions using a standard SDS/Tris/glycine running buffer (BioRad). Following electrophoresis, one gel was stained with Coomassie brilliant blue R250 (BioRad) and then destained to visualize novel IPTG-inducible protein(s). The second gel was electroblotted onto a PVDF membrane (0.45 micron pore size, Novex) for ˜2 hrs at 4° C. using a BioRad Mini-Protean II blotting apparatus and Towbin's methanol (20%) transfer buffer. Blocking of the membrane and antibody incubations were performed according to methods well known in the art. A monoclonal anti-RGS (His)3 antibody, followed by a second rabbit anti-mouse antibody conjugated to HRP (QIAGEN), were used to confirm the expression and identity of the recombinant protein. Visualization of the anti-His antibody reactive pattern was achieved using either an ABT insoluble substrate or using Hyperfilm with the Amersham ECL chemiluminescence system.
Example 2
Production of Recombinant Protein
Bacterial Strain
[0335] A recombinant expression strain of E. coli M15(pREP4) containing a plasmid (pQE30) or BL21::DE3 containing plasmid pET24d encoding staphylococcal protein was used to produce cell mass for purification of recombinant protein.
Media
[0336] The fermentation medium used for the production of recombinant protein consisted of 2× YT broth (Difco) containing 100 μg/ml Ap and/or 30 μl/ml Km. Antifoam was added to medium for the fermentor at 0.25 ml/L (Antifoam 204, Sigma). To induce expression of the recombinant protein, IPTG (Isopropyl β-D-Thiogalactopyranoside) was added to the fermentor (1 mM, final).
Production of Recombinant Proteins
[0337] Under Native Conditions
[0338] IPTG was added at a final concentration of 1 mM and the culture was grown for 4 additional hours. The culture was then centrifuged at 6,000 rpm for 10 minutes and the pellet was resuspended in phosphate buffer (50 mM K2HPO4, KH2PO4 pH 7) including a protease inhibitor cocktail. This sample was subjected to French pressure lysis using 1500 bar pressure (2 runs). After centrifugation for 30 minutes at 15,000 rpm, the supernatant was reserved for further purification and NaCl was added to 0.5M. The sample was then loaded on a Ni-NTA resin (XK 16 column Pharmacia, Ni-NTA resin QIAGEN) conditioned in 50 mM K2HPO4, KH2PO4 pH 7. After loading the sample, the column was washed with Buffer A (0.2M NaH2PO4 pH7, 0.3M NaCl, 10% glycerol). To elute bound protein, a step gradient ws used where different proportions of buffer B (0.2M .sub.NaH2PO4 pH7, 0.3M NaCl, 10% glycerol and 200 mM imidazole) were added to buffer A. The proportion of buffer B was gradually increased from 10% to 100%. After purification, eluted fraction containing the protein were pooled, concentrated and dialysed against 0.002 M KH2PO4/K2HPO4 pH 7, 0.15 M NaCl.
[0339] This method was used to purify ClfA, SdrG, IsdA, IsaB, HarA, Atl-glucosamine and alpha toxin.
[0340] Under Denaturing Conditions
[0341] IPTG was added at a final concentration of 1 mM and the culture was grown for 4 additional hours. The culture was then centrifuged at 6,000 rpm for 10 minutes and the pellet was resuspended in phosphate buffer (50 mM K2HPO4, KH2PO4 pH 7) including a protease inhibitor cocktail. This sample was subjected to French pressure lysis using 1500 bar pressure (2 runs). After centrifugation for 30 minutes at 15,000 rpm, the pellet was washed with phosphate buffer including 1M urea. The sample was centrifuged for 30 mins at 15000 rpm and the pellet was resuspended in 8M urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris-HCl pH8 and kept overnight at room temperature. The sample was centrifuged for 20 minutes at 15000 rpm and the supernatant was collected for further purification. The sample was then loaded on a Ni-NTA resin (XK 16 column Pharmacia, Ni-NTA resin QIAGEN) conditioned in 8M urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris-HCl pH8. After passage of the flowthrough, the column was washed successively with buffer A (8M Urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris, pH 8.0), buffer C (8M Urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris, pH 6.3), buffer D (8M Urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris, pH 5.9) and buffer E (8M Urea, 0.1M NaH2PO4, 0.5M NaCl, 0.01M Tris, pH 4.5). The recombinant protein was eluted from the column during washes with buffer D and E. The denatured, recombinant protein could be solubilized in a solution devoid of urea. For this purpose, denatured protein contained in 8M urea was successively dialyzed against 4M urea, 0.1M Na2PO4, 0.01M Tris-HCl, pH7.1, 2M urea, 0.1M NaH2PO4, 0.01M Tris-HCl, pH 7.1, 0.5M arginine and 0.002M KH2PO2/K2HPO4 pH7.1, 0.15M NaCl, 0.5M arginine.
[0342] This method was used to purify Ebh (H2 fragment), AaA, SdrC, FnbpA, Sbi, Atl-amidase and IsaA.
[0343] The purified proteins were analyzed by SDS-PAGE. The results for one protein purified under native conditions (alpha toxin) and one protein purified under denaturing conditions (SdrC) are shown in FIGS. 3 and 4.
Example 3
Preparation of Polysaccharides
[0344] PIA (PNAG) is prepared as described in Joyce et al., 2003, Carbohydrate Research 338; 903-922.
[0345] Type 5 and type 8 polysaccharides is extracted from S. Aureus as described in Infection and Immunity 58(7); 2367.
Activation and Coupling Chemistry
[0346] Native polysaccharide is dissolved in NaCl 2M or in water. The optimal polysaccharide concentration is evaluated for all the serotypes and is between 2 mg/ml and 5 mg/ml.
[0347] From a 100 mg/ml stock solution in acetonitrile, CDAP (CDAP/PS ratio: 0.75 mg/mg PS) is added to the polysaccharide solution. 1.5 minute later, 0.2M triethylamine is added to obtain the specific activation pH (pH 8.5-10.0). The activation of the polysaccharide is performed at this pH during 2 minutes at 25° C. The carrier protein is added to the activated polysaccharide in an amount sufficient to give a 1/1 molar ratio and the coupling reaction is performed at the specific pH for 1 hour.
[0348] Then, the reaction is quenched with glycine for 30 minutes at 25° C. and overnight at 4° C.
[0349] The conjugates are purified by gel filtration using a Sephacryl 500HR gel filtration column equilibrated with 0.2M NaCl.
[0350] The carbohydrate and protein contents of the eluted fractions are determined. The conjugates are pooled and sterile filtered on a 0.22 μm sterilizing membrane. The PS/Protein ratios in the conjugate preparations are determined.
Characterization
[0351] Each conjugate is characterized for protein and polysaccharide content.
[0352] The polysaccharide content is measured by the Resorcinol test and the protein content by the Lowry test. The final PS/PD ratio (w/w) is determined by the ratio of the concentrations.
Residual DMAP Content (ng/μg PS)
[0353] The activation of the polysaccharide with CDAP introduces a cyanate group in the polysaccharide and DMAP (4-dimethylamino-pyridin) is liberated. The residual DMAP content is determined by a specific assay developed and validated at GSK.
Free Polysaccharide Content (%)
[0354] The free polysaccharide content on conjugates kept at 4° C. or stored 7 days at 37° C. is determined on the supernatant obtained after incubation with α-carrier antibodies and saturated ammonium sulfate, followed by a centrifugation.
[0355] An α-PS/α-PS ELISA is used for the quantification of free polysaccharide in the supernatant. The absence of conjugate is also controlled by an α-carrier/α-PS ELISA.
Example 4
Formulation
Adjuvant Compositions
[0356] Protein, either individually or together, from the above examples may be formulated with the staphylococcal polysaccharide combination and as adjuvant, the formulation may comprise a mixture of 3 de-O-acylated monophosphoryl lipid A (3D-MPL) and aluminum hydroxide, or of 3 de-O-acylated monophosphoryl lipid A (3D-MPL) and aluminum phosphate, or 3D-MPL and/or QS21 optionally in an oil/water emulsion, and optionally formulated with cholesterol, or aluminum salt alone, preferably aluminum phosphate.
[0357] 3D-MPL: is a chemically detoxified form of the lipopolysaccharide (LPS) of the Gram-negative bacteria Salmonella minnesota.
[0358] Experiments performed at GSK Biologicals have shown that 3D-MPL combined with various vehicles strongly enhances both the humoral and a TH1 type of cellular immunity.
[0359] QS21: is one saponin purified from a crude extract of the bark of the Quillaja Saponaria Molina tree, which has a strong adjuvant activity: it activates both antigen-specific lymphoproliferation and CTLs to several antigens.
[0360] Vaccine containing an antigen of the invention containing 3D-MPL and alum may be prepared in analogous manner to that described in WO93/19780 or 92/16231.
[0361] Experiments performed at GSK Biologicals have demonstrated a clear synergistic effect of combinations of 3D-MPL and QS21 in the induction of both humoral and TH1 type cellular immune responses. Vaccines containing an antigen such antigens are described in U.S. Pat. No. 5,750,110.
[0362] An oil/water emulsion may be composed of 2 oils (a tocopherol and squalene), and of PBS containing TWEEN 80 as emulsifier. The emulsion comprised 5% squalene 5% tocopherol 0.4% TWEEN 80 and had an average particle size of 180 nm and is known as SB62 (see WO 95/17210).
[0363] Experiments performed at GSK Biologicals have proven that the adjunction of this O/W emulsion to MPL/QS21 further increases their immunostimulant properties.
Preparation of Emulsion SB62 (2 Fold Concentrate)
[0364] Tween 80 is dissolved in phosphate buffered saline (PBS) to give a 2% solution in the PBS. To provide 100 ml two fold concentrate emulsion 5 g of DL alpha tocopherol and 5 ml of squalene are vortexed to mix thoroughly. 90 ml of PBS/TWEEN solution is added and mixed thoroughly. The resulting emulsion is then passed through a syringe and finally microfluidised by using an M110S microfluidics machine. The resulting oil droplets have a size of approximately 180 nm.
Example 5
Animal Experiments
[0365] Female CD-1 mice, 8 to 10 weeks old, are obtained from Charles River Laboratories, Kingston, Mass. For lethality studies, five groups of 9 to 11 CD-1 mice are challenged intraperitoneally (i.p.) with serial dilutions of S. Aureus grown on CSA plates. The inocular sizes range from ˜1010 to 108 CFU/mouse. Mortality is assessed on a daily basis for 3 days. The 50% lethal doses (LD50s) is estimated by using a probit model of the dose-response relationship. The null hypothesis of common LD50s was tested by the likelihood ratio test. Sublethal bacteremia is initiated by challenging groups of 8 to 20 mice by the intravenous (i.v.) route with ˜2×106 CFU/mouse or by the i.p. route with ˜2×107 CFU/mouse. After inoculation separate groups of animals are bled from the tail at specified times, and the bacteremia levels are estimated by quantitative plate counts performed in duplicate on tryptic soy agar plates with 5% sheep blood (Becton Dickinson Microbiology Systems). Statistical significance is determined with the Welch modification of the unpaired Student's t test.
Example 6
General Methodology of Determining Antibody Responses in Various Mammals
[0366] The sera were tested for IgG antibodies to the staphylococcal polysaccharides by an ELISA. Briefly, purified capsular polysaccharides from ATCC (Rockville, Md., 20852) are coated at 25 μg/ml in phosphate buffered saline (PBS) on high binding microtitre plates (Nunc Maxisorp) overnight at 4C. The plates are blocked with 10% fetal calf serum (FCS), 1 hour at 37C. Serum samples are pre-incubated with the 20 μg/ml cell-wall polysaccharide (Statens Serum Institute, Copenhagen) and 10% FCS at room temperature for 30 minutes to neutralize antibodies to this antigen. The samples are then diluted two-fold on the microplate in 10% FCS in PBS, and equilibrated at room temperature for 1 hour with agitation. After washing, the microplates are equilibrated with peroxidase labelled anti-human IgG Fc monoclonal antibody (HP6043-HRP, Stratech Scientific Ltd) diluted 1:4000 in 10% FCS in PBS for 1 hour at room temperature with agitation. The ELISA is performed to measure rat IgG using Jackson ImmunoLaboratories Inc. peroxidase-conjugated AffiniPure Goat anti-Rat IgG (H+L) (code 112-035-003) at 1:5000. The titration curves are referenced to standard sera for each serotype using logistic log comparison by SoftMax Pro. The polysaccharide concentrations used to coat the ELISA plate are 10-20 μg/ml. The color is developed using 4 mg OPD (Sigma) per 10 ml pH 4.5 0.1M citrate buffer with 14 μl H2O2 for 15 minutes in the dark at room temperature. The reaction is stopped with 50 μl HCl, and the optical density is read at 490 nm relative to 650 nm. IgG concentrations are determined by reference of titration points to the calibration curve modeled using a 4-parameter logistic log equation calculated by SoftMax Pro software.
[0367] The ELISA to measure the murine and rat IgG to the staphylococcal polysaccharides is similar with the following exceptions. Jackson ImmunoLaboratories Inc. peroxidase-conjugated AffiniPure Goat Anti-mouse IgG (H+L) and AffiniPure Goat Anti-rat IgG (H+L) were employed to detect bound IgG.
[0368] HP6043-HRP reacts equally with human and Rhesus purified IgG, and so this reagent is used for Rhesus antiserum.
[0369] The protein ELISA is performed similarly to the polysaccharide ELISA with the following modifications. The protein is coated overnight at 2.0 μg/ml in PBS. The serum samples are diluted in PBS containing 10% fetal calf serum and 0.1% polyvinyl alcohol. Bound human antibody is detected using Sigma Peroxidase-conjugated goat affinity purified antibody to Human IgG Fc (reference A-2290).
Example 7
Opsonophagocytosis Assay
[0370] The in vitro opsonophagocytic killing of S. Aureus by human polymorphonuclear leukocytes (PMNs) is performed as described in Xu et al., 1992 Infect. Immune. 60; 1358. Human PMNs are prepared from heparinized blood by sedimentation in 3% dextran T-250. The opsonic reaction mixture (1 ml) contains ˜106 PMNs in RPMI 1640 medium supplemented with 10% heat-inactivated fetal calf serum, ˜108 CFU of S-aureus, and 0.1 ml of the test serum or IgG preparation. Hyperimmunized rabbit serum is used as a positive control, and 0.1 ml of nonimmune rabbit serum was used as a complete source for the IgG samples. The reaction mixtures are incubated at 37° C., and bacterial samples are transferred at 0, 60, and 120 min into water and subsequently diluted, spread on tryptic soy agar plates, and incubated at 37° C. for bacterial count after overnight incubation.
Example 8
Immunogenicity of Staphylococcal Proteins in Mice and Rabbits
[0371] Animals were immunized with purified staphylococcal proteins in order to generate hyper-immune sera. Mice were immunized three times (days 0, 14 and 28) with 10 μg of each proteins adjuvanted in Specol. Rabbits were immunized three times (days 0, 21 and 42) with 20 μg of each proteins adjuvanted in Specol. Immune sera were collected and evaluated in anti-protein and anti-killed whole cells ELISA.
Anti-Protein ELISA
[0372] The purified protein was coated at 1 μg/ml in phosphate buffered saline (PBS) on high binding microtitre plates (Nunc Maxisorp) overnight at 4° C. The plates were blocked with PBS-BSA 1%, for 30 min at RT with agitation. The test samples were then diluted 1/1000 and incubated at room temperature for 1 hour with agitation. After washing, bound murine or rabbit antibody was detected using Jackson ImmunoLaboratories Inc. peroxidase-conjugated AffiniPure Goat Anti-Mouse IgG (H+L) (ref: 115-035-003) or AffiniPure Goat Anti-Rabbit IgG (H+L) (ref: 11-035-003) diluted 1:5000 in PBS-tween 0.05%. The detection antibodies were incubated for 30 min. at room temperature with agitation. The color was developed using 4 mg OPD (Sigma)+5 μl H2O2 per 10 ml pH 4.5 0.1M citrate buffer for 15 minutes in the dark at room temperature. The reaction was stopped with 50 μl HCl, and the optical density was read at 490 nm relative to 650 nm.
[0373] The O.D. for a 1/1000 dilution of Post III was compared to the O.D. obtained with the same dilution of Pre-immune sera.
[0374] Results generated with mice and rabbit sera are presented in FIG. 5. A good seroconversion against each antigen was observed. Evaluation of sera directed against SBI was impaired due to the Ig binding activity of this protein.
Anti-Killed Whole Cells ELISA
[0375] Killed whole cells (heat or formaldehyde inactivated) from S. Aureus type 5 and 8 or S. Epidermidis strain Hay were coated at 20 μg/ml in phosphate buffered saline (PBS) on high binding microtitre plates (Nunc Maxisorp) overnight at 4° C. with evaporation. The plates were blocked with PBS-BSA 1% 30 min at room temperature with agitation. Protein A was neutralized by addition of 10 μg/ml of Affinity Purified Chicken anti-ProteinA (ICL ref: CPA-65A-2) diluted in PBS-tween 0.05% followed by incubation for 1 hour at room temperature. The test samples were then diluted two-fold on the microplate in PBS-0.05% from a starting dilution at 1/10 and incubated 1 hour at room temperature with agitation. After washing, bound murine or rabbit antibody was detected using Jackson ImmunoLaboratories Inc. peroxidase-conjugated AffiniPure Goat Anti-Mouse IgG (H+L) (ref: 115-035-003) or AffiniPure Goat Anti-Rabbit IgG (H+L) (ref: 11-035-003) diluted 1:5000 in PBS-tween 0.05%. This detection antibodies were incubated for 30 min. at room temperature with agitation. The color was developed using 4 mg OPD (Sigma) +5 μl H2O2 per 10 ml pH 4.5 0.1M citrate buffer for 15 minutes in the dark, at room temperature. The reaction was stopped with 50 μl HCl, and the optical density was read at 490 nm relative to 650 nm.
[0376] It should be noted that expression levels of proteins in staphylococci will vary depending on culture conditions. Therefore a negative result may reflect the choice of incorrect culture conditions rather than a lack of immunogenicity.
[0377] The results using mice sera are shown in Table 5 and some of the graphs are shown in FIG. 6. A weak recognition of S. Aureus strain 5 is observed with sera directed against SdrC, FnbpA, Ebh, Sbi and IsaA. Recognition of S. Aureus strain 8 is only observed with the serum directed against Sbi. Weak recognition of S. Epidermidis Hay is observed with sera directed against Atl amidase, MRP, IsdA, IsaA, Ebh, Aaa and Sbi.
[0378] A selection of results generated using rabbit sera are shown in FIG. 7 and summarized in Table 6. Very good recognition of the three strains was observed with IsaA and IsdB. A weak recognition of the three stains was observed with HarA although animals only received one injection rather than the three injections used for the other proteins.
TABLE-US-00010 TABLE 5 Protein name React on SA5 React on SA8 React on SE Hay IsaA (+) (+) (+) ClfA - (+) (+) Atl amidase - - ++ SdrG - - - Glucosamidase - - - IsdA - - ++ Alpha toxin - - - SrdC ++ (+) - Ebh + - + AaA - - ++ MRP - - ++ Sbi ++ ++ +++ FnbpA + + (+)
TABLE-US-00011 TABLE 6 Protein name React on SA5 React on SA8 React on SE Hay IsaA +++ +++ +++ ClfA + ++ ++ Atl amidase - ++ + IsdB +++ +++ +++ SdrG + + + Glucosamidase - - - HarA (1 inject.) + + + IsdA - - - Alpha toxin - - + SrdC - - - Ebh - + - AaA - - - MRP - - ++ Sbi - +++ - FnbpA - ++ ++
Example 9
Efficacy of Combinations of Staphylococcal Proteins in a Nasal Colonization Model
[0379] Fifteen groups of three cotton rats were inoculated with combinations of eight staphylococcal antigens and five cotton rats which acted as controls were treated with no antigen. These sixteen groups are as follows:
[0380] Group 1--Atl-glucosamine, Atl-amidase, AAA, alpha toxin, SdrC, SdrG, Ebh, Sbi
[0381] Group 2--Atl-glucosamine, Atl-amidase , IsdA, IsdB, ClfA, SdrC, Ebh, FnbpA
[0382] Group 3--Atl-glucosamine, Atl-amidase, HarA, IsdA, MRP, IsdB, AAA, alpha toxin
[0383] Group 4--Atl-glucosamine, HarA, IsdA, AAA, ClfA, IsaA, Ebh, Sbi
[0384] Group 5--HarA, MRP, AAA, alpha toxin, ClfA, SdrC, Ebh, FnbpA
[0385] Group 6--IsdA, IsdB, AAA, alpha toxin, ClfA, SdrG, Sbi, FnbpA
[0386] Group 7--Atl-amidase, IsdA, MRP, AAA, IsaA, SdrG, Ebh, FnbpA
[0387] Group 8--Control
[0388] Group 9--Atl-glucosamine, IsdA, MRP, alpha toxin, IsaA, SdrC, Sbi, FnbpA
[0389] Group 10--Atl-glucosamine, MRP, IsdB, AAA, ClfA, IsaA, SdrC, SdrG
[0390] Group 11--Atl-amidase, MRP, IsdB, alpha toxin, ClfA, IsaA, Ebh, Sbi
[0391] Group 12--Atl-glucosamine, HarA, IsdB, alpha toxin, IsaA, SdrG, Ebh, FnbpA
[0392] Group 13--Atl-amidase, HarA, IsdB, AAA, IsaA, SdrC, Sbi, FnbpA
[0393] Group 14--Atl-glucosamine, Atl-amidase, HarA, MRP, ClfA, SdrG, Sbi, FnbpA
[0394] Group 15--Atl-amidase, HarA, IsdA, alpha toxin, ClfA, IsaA, SdfC, SdrG
[0395] Group 16--HarA, IsdA, MRP, IsdB, SdrC, SdrG, Ebh, Sbi
[0396] Each mix of antigens contained 3 μg of each antigen mixed with an adjuvant made of liposomes containing MPL and QS21. The cotton rats were inoculated three times on days 1, 14 and 28 of the experiment. Two weeks after inoculation, the efficacy of the immunizations were assessed using a nasal colonization assay as described in Kokai-Kun et al., (2003) Antimicrob. Agents Chemother. 47; 1589-1597.
[0397] Classical multiple linear regression analysis was carried out on the data using "Design Expert 6" software. The presence of an antigen was coded as +1 and the absence of an antigen by -1. Using the equation of the model it was possible to determine which antigens were the key antigens which produced a large decrease in the number of colonies per nose.
Results
[0398] The results of the nasal colonization assay are shown in Table 7. The control group had a mean log CFU/nose of 3.51335 and a decrease in nasal colonization could be see for all the groups of cotton rats inoculated with staphylococcal proteins. Groups 4, 9 and 13 showed the greatest decrease in nasal colonization with a decrease of over 2 logs in CFU/nose. Groups 12 and 16 also gave good results, showing a decrease of about 2 logs in CFU/nose.
TABLE-US-00012 TABLE 7 Group Mean observed Log CFU/nose Predicted Log CFU/nose 1 1.77527 2.03560 2 2.90435 2.52684 3 1.96556 2.23033 4 1.27748 1.21872 5 1.67304 1.93128 6 2.79745 2.98193 7 2.21481 2.30705 8 3.51355 3.47317 9 1.22480 1.44080 10 2.03085 1.93204 11 2.02522 1.81581 12 1.53402 1.70996 13 1.36063 1.49100 14 2.31201 1.73909 15 2.22979 1.98223 16 1.58109 1.44004
[0399] The contribution of specific antigens within the antigen mix was calculated using multiple regression analysis of the nasal colonization data. The final model contains the seven best antigens. Results for these antigens are shown in Table 8. Within the context of the protein mix, the inclusion of HarA gave the greatest decrease in nasal colonization, followed by IsaA, Sbi, SdrC, autolysin-glucosamine, MRP and Ebh.
TABLE-US-00013 TABLE 8 Effects in difference of logCFU/nose and ratio of CFU/nose for the seven best antigens in the model and corresponding p-values. Effect Reduction Cumulative Cumulative antigen prob > F estimate ratio effect ratio HarA 0.033 -0.596 3.9 -0.596 3.9 IsaA 0.046 -0.558 3.6 -1.154 14.3 Sbi 0.077 -0.491 3.1 -1.645 44.2 SdrC 0.22 -0.337 2.2 -1.982 96.0 Atl-glucos 0.238 -0.324 2.1 -2.306 202.2 MRP 0.239 -0.323 2.1 -2.629 425.3 Ebh 0.297 -0.286 1.9 -2.914 821.0
Sequence CWU
1
1
1541533PRTStaphylococcus sp. 1Met Leu Gln Val Thr Asp Val Ser Leu Arg Phe
Gly Asp Arg Lys Leu1 5 10
15 Phe Glu Asp Val Asn Ile Lys Phe Thr Glu Gly Asn Cys Tyr Gly Leu
20 25 30 Ile Gly Ala
Asn Gly Ala Gly Lys Ser Thr Phe Leu Lys Ile Leu Ser 35
40 45 Gly Glu Leu Asp Ser Gln Thr Gly
His Val Ser Leu Gly Lys Asn Glu 50 55
60 Arg Leu Ala Val Leu Lys Gln Asp His Tyr Ala Tyr Glu
Asp Glu Arg65 70 75 80
Val Leu Asp Val Val Ile Lys Gly His Glu Arg Leu Tyr Glu Val Met
85 90 95 Lys Glu Lys Asp Glu
Ile Tyr Met Lys Pro Asp Phe Ser Asp Glu Asp 100
105 110 Gly Ile Arg Ala Ala Glu Leu Glu Gly Glu
Phe Ala Glu Met Asn Gly 115 120
125 Trp Asn Ala Glu Ala Asp Ala Ala Asn Leu Leu Ser Gly Leu
Gly Ile 130 135 140
Asp Pro Thr Leu His Asp Lys Lys Met Ala Glu Leu Glu Asn Asn Gln145
150 155 160 Lys Ile Lys Val Leu
Leu Ala Gln Ser Leu Phe Gly Glu Pro Asp Val 165
170 175 Leu Leu Leu Asp Glu Pro Thr Asn Gly Leu
Asp Ile Pro Ala Ile Ser 180 185
190 Trp Leu Glu Asp Phe Leu Ile Asn Phe Asp Asn Thr Val Ile Val
Val 195 200 205 Ser
His Asp Arg His Phe Leu Asn Asn Val Cys Thr His Ile Ala Asp 210
215 220 Leu Asp Phe Gly Lys Ile
Lys Val Tyr Val Gly Asn Tyr Asp Phe Trp225 230
235 240 Tyr Gln Ser Ser Gln Leu Ala Gln Lys Met Ala
Gln Glu Gln Asn Lys 245 250
255 Lys Lys Glu Glu Lys Met Lys Glu Leu Gln Asp Phe Ile Ala Arg Phe
260 265 270 Ser Ala Asn
Ala Ser Lys Ser Lys Gln Ala Thr Ser Arg Lys Lys Gln 275
280 285 Leu Glu Lys Ile Glu Leu Asp Asp
Ile Gln Pro Ser Ser Arg Arg Tyr 290 295
300 Pro Phe Val Lys Phe Thr Pro Glu Arg Glu Ile Gly Asn
Asp Leu Leu305 310 315
320 Ile Val Gln Asn Leu Ser Lys Thr Ile Asp Gly Glu Lys Val Leu Asp
325 330 335 Asn Val Ser Phe
Thr Met Asn Pro Asn Asp Lys Ala Ile Leu Ile Gly 340
345 350 Asp Ser Glu Ile Ala Lys Thr Thr Leu
Leu Lys Ile Leu Ala Gly Glu 355 360
365 Met Glu Pro Asp Glu Gly Ser Phe Lys Trp Gly Val Thr Thr
Ser Leu 370 375 380
Ser Tyr Phe Pro Lys Asp Asn Ser Glu Phe Phe Glu Gly Val Asn Met385
390 395 400 Asn Leu Val Asp Trp
Leu Arg Gln Tyr Ala Pro Glu Asp Glu Gln Thr 405
410 415 Glu Thr Phe Leu Arg Gly Phe Leu Gly Arg
Met Leu Phe Ser Gly Glu 420 425
430 Glu Val Lys Lys Lys Ala Ser Val Leu Ser Gly Gly Glu Lys Val
Arg 435 440 445 Cys
Met Leu Ser Lys Met Met Leu Ser Ser Ala Asn Val Leu Leu Leu 450
455 460 Asp Glu Pro Thr Asn His
Leu Asp Leu Glu Ser Ile Thr Ala Val Asn465 470
475 480 Asp Gly Leu Lys Ser Phe Lys Gly Ser Ile Ile
Phe Thr Ser Tyr Asp 485 490
495 Phe Glu Phe Ile Asn Thr Ile Ala Asn Arg Val Ile Asp Leu Asn Lys
500 505 510 Gln Gly Gly
Val Ser Lys Glu Ile Pro Tyr Glu Glu Tyr Leu Gln Glu 515
520 525 Ile Gly Val Leu Lys 530
2535PRTStaphylococcus sp. 2Met Leu Gln Val Thr Asp Val Ser Leu Arg
Phe Gly Asp Arg Lys Leu1 5 10
15 Phe Glu Asp Val Asn Ile Lys Phe Thr Glu Gly Asn Cys Tyr Gly
Leu 20 25 30 Ile
Gly Ala Asn Gly Ala Gly Lys Ser Thr Phe Leu Lys Ile Leu Ser 35
40 45 Gly Glu Ile Asp Ser Gln
Thr Gly His Val Ser Leu Gly Lys Asp Glu 50 55
60 Arg Leu Ala Val Leu Lys Gln Asp His Phe Ala
Tyr Glu Asp Glu Arg65 70 75
80 Val Leu Asp Val Val Ile Lys Gly His Glu Arg Leu Tyr Gln Val Met
85 90 95 Lys Glu Lys
Asp Glu Ile Tyr Met Lys Pro Asp Phe Ser Asp Glu Asp 100
105 110 Gly Ile Arg Ala Ala Glu Leu Glu
Gly Glu Phe Ala Glu Met Asn Gly 115 120
125 Trp Asn Ala Glu Ala Asp Ala Ala Asn Leu Leu Ser Gly
Leu Gly Ile 130 135 140
Glu Pro Asp Leu His Asp Lys Asn Met Ser Glu Leu Glu Asn Asn Gln145
150 155 160 Lys Val Lys Val Leu
Leu Ala Gln Ser Leu Phe Gly Asp Pro Asp Val 165
170 175 Leu Leu Leu Asp Glu Pro Thr Asn Gly Leu
Asp Ile Pro Ala Ile Ser 180 185
190 Trp Leu Glu Asp Phe Leu Ile Asn Phe Glu Asn Thr Val Ile Val
Val 195 200 205 Ser
His Asp Arg His Phe Leu Asn Asn Val Cys Thr His Ile Ala Asp 210
215 220 Leu Asp Phe Gly Lys Ile
Lys Leu Tyr Val Gly Asn Tyr Asp Phe Trp225 230
235 240 Tyr Gln Ser Ser Gln Leu Ala Gln Lys Met Ala
Gln Glu Gln Asn Lys 245 250
255 Lys Lys Glu Glu Lys Met Lys Glu Leu Gln Asp Phe Ile Ala Arg Phe
260 265 270 Ser Ala Asn
Ala Ser Lys Ser Lys Gln Ala Thr Ser Arg Lys Lys Gln 275
280 285 Leu Glu Lys Ile Glu Leu Asp Asp
Ile Gln Pro Ser Ser Arg Arg Tyr 290 295
300 Pro Tyr Val Lys Phe Thr Pro Glu Arg Glu Ile Gly Asn
Asp Leu Leu305 310 315
320 Thr Val Glu Asn Leu Ser Lys Thr Ile Asp Gly Glu Lys Val Leu Asp
325 330 335 Asn Val Ser Phe
Thr Met Asn Pro Asn Asp Lys Ala Ile Leu Val Gly 340
345 350 Asp Ser Glu Ile Ala Lys Thr Thr Leu
Leu Lys Ile Leu Ala Gly Glu 355 360
365 Met Glu Pro Asp Glu Gly Thr Phe Lys Trp Gly Val Thr Thr
Ser Leu 370 375 380
Ser Tyr Phe Pro Lys Asp Asn Ser Glu Phe Phe Asp Gly Val Asp Met385
390 395 400 Asn Leu Val Glu Trp
Leu Arg Gln Tyr Ala Pro Glu Asp Glu Gln Thr 405
410 415 Glu Thr Phe Leu Arg Gly Phe Leu Gly Arg
Met Leu Phe Ser Gly Glu 420 425
430 Glu Val Lys Lys Lys Ala Ser Val Leu Ser Gly Gly Glu Lys Val
Arg 435 440 445 Cys
Met Leu Ser Lys Met Met Leu Ser Ser Ala Asn Val Leu Leu Leu 450
455 460 Asp Glu Pro Thr Asn His
Leu Asp Leu Glu Ser Ile Thr Ala Val Asn465 470
475 480 Asp Gly Leu Lys Ser Phe Lys Gly Ser Ile Ile
Phe Thr Ser Tyr Asp 485 490
495 Phe Glu Phe Ile Asn Thr Ile Ala Asn Arg Val Ile Asp Leu Asn Gln
500 505 510 Ala Gly Ala
Leu Ser Lys Glu Val Pro Tyr Glu Glu Tyr Leu Gln Glu 515
520 525 Ile Gly Val Leu Gln Asn Asn
530 535 3434PRTStaphylococcus sp. 3Met Pro Ile Ile Thr
Asp Val Tyr Ala Arg Glu Val Leu Asp Ser Arg1 5
10 15 Gly Asn Pro Thr Val Glu Val Glu Val Leu
Thr Glu Ser Gly Ala Phe 20 25
30 Gly Arg Ala Leu Val Pro Ser Gly Ala Ser Thr Gly Glu His Glu
Ala 35 40 45 Val
Glu Leu Arg Asp Gly Asp Lys Ser Arg Tyr Leu Gly Lys Gly Val 50
55 60 Thr Lys Ala Val Glu Asn
Val Asn Glu Ile Ile Ala Pro Glu Ile Ile65 70
75 80 Glu Gly Glu Phe Ser Val Leu Asp Gln Val Ser
Ile Asp Lys Met Met 85 90
95 Ile Ala Leu Asp Gly Thr Pro Asn Lys Gly Lys Leu Gly Ala Asn Ala
100 105 110 Ile Leu Gly
Val Ser Ile Ala Val Ala Arg Ala Ala Ala Asp Leu Leu 115
120 125 Gly Gln Pro Leu Tyr Lys Tyr Leu
Gly Gly Phe Asn Gly Lys Gln Leu 130 135
140 Pro Val Pro Met Met Asn Ile Val Asn Gly Gly Ser His
Ser Asp Ala145 150 155
160 Pro Ile Ala Phe Gln Glu Phe Met Ile Leu Pro Val Gly Ala Thr Thr
165 170 175 Phe Lys Glu Ser
Leu Arg Trp Gly Thr Glu Ile Phe His Asn Leu Lys 180
185 190 Ser Ile Leu Ser Lys Arg Gly Leu Glu
Thr Ala Val Gly Asp Glu Gly 195 200
205 Gly Phe Ala Pro Lys Phe Glu Gly Thr Glu Asp Ala Val Glu
Thr Ile 210 215 220
Ile Gln Ala Ile Glu Ala Ala Gly Tyr Lys Pro Gly Glu Glu Val Phe225
230 235 240 Leu Gly Phe Asp Cys
Ala Ser Ser Glu Phe Tyr Glu Asn Gly Val Tyr 245
250 255 Asp Tyr Ser Lys Phe Glu Gly Glu His Gly
Ala Lys Arg Thr Ala Ala 260 265
270 Glu Gln Val Asp Tyr Leu Glu Gln Leu Val Asp Lys Tyr Pro Ile
Ile 275 280 285 Thr
Ile Glu Asp Gly Met Asp Glu Asn Asp Trp Asp Gly Trp Lys Gln 290
295 300 Leu Thr Glu Arg Ile Gly
Asp Arg Val Gln Leu Val Gly Asp Asp Leu305 310
315 320 Phe Val Thr Asn Thr Glu Ile Leu Ala Lys Gly
Ile Glu Asn Gly Ile 325 330
335 Gly Asn Ser Ile Leu Ile Lys Val Asn Gln Ile Gly Thr Leu Thr Glu
340 345 350 Thr Phe Asp
Ala Ile Glu Met Ala Gln Lys Ala Gly Tyr Thr Ala Val 355
360 365 Val Ser His Arg Ser Gly Glu Thr
Glu Asp Thr Thr Ile Ala Asp Ile 370 375
380 Ala Val Ala Thr Asn Ala Gly Gln Ile Lys Thr Gly Ser
Leu Ser Arg385 390 395
400 Thr Asp Arg Ile Ala Lys Tyr Asn Gln Leu Leu Arg Ile Glu Asp Glu
405 410 415 Leu Phe Glu Thr
Ala Lys Tyr Asp Gly Ile Lys Ser Phe Tyr Asn Leu 420
425 430 Asp Lys4434PRTStaphylococcus sp.
4Met Pro Ile Ile Thr Asp Val Tyr Ala Arg Glu Val Leu Asp Ser Arg1
5 10 15 Gly Asn Pro Thr Val
Glu Val Glu Val Leu Thr Glu Ser Gly Ala Phe 20
25 30 Gly Arg Ala Leu Val Pro Ser Gly Ala Ser
Thr Gly Glu His Glu Ala 35 40 45
Val Glu Leu Arg Asp Gly Asp Lys Ser Arg Tyr Leu Gly Lys Gly
Val 50 55 60 Thr
Lys Ala Val Glu Asn Val Asn Glu Met Ile Ala Pro Glu Ile Val65
70 75 80 Glu Gly Glu Phe Ser Val
Leu Asp Gln Val Ser Ile Asp Lys Met Met 85
90 95 Ile Gln Leu Asp Gly Thr His Asn Lys Gly Lys
Leu Gly Ala Asn Ala 100 105
110 Ile Leu Gly Val Ser Ile Ala Val Ala Arg Ala Ala Ala Asp Leu
Leu 115 120 125 Gly
Gln Pro Leu Tyr Lys Tyr Leu Gly Gly Phe Asn Gly Lys Gln Leu 130
135 140 Pro Val Pro Met Met Asn
Ile Val Asn Gly Gly Ser His Ser Asp Ala145 150
155 160 Pro Ile Ala Phe Gln Glu Phe Met Ile Leu Pro
Val Gly Ala Glu Ser 165 170
175 Phe Lys Glu Ser Leu Arg Trp Gly Ala Glu Ile Phe His Asn Leu Lys
180 185 190 Ser Ile Leu
Ser Glu Arg Gly Leu Glu Thr Ala Val Gly Asp Glu Gly 195
200 205 Gly Phe Ala Pro Arg Phe Glu Gly
Thr Glu Asp Ala Val Glu Thr Ile 210 215
220 Ile Lys Ala Ile Glu Lys Ala Gly Tyr Lys Pro Gly Glu
Asp Val Phe225 230 235
240 Leu Gly Phe Asp Cys Ala Ser Ser Glu Phe Tyr Glu Asn Gly Val Tyr
245 250 255 Asp Tyr Thr Lys
Phe Glu Gly Glu His Gly Ala Lys Arg Ser Ala Ala 260
265 270 Glu Gln Val Asp Tyr Leu Glu Glu Leu
Ile Gly Lys Tyr Pro Ile Ile 275 280
285 Thr Ile Glu Asp Gly Met Asp Glu Asn Asp Trp Glu Gly Trp
Lys Gln 290 295 300
Leu Thr Asp Arg Ile Gly Asp Lys Val Gln Leu Val Gly Asp Asp Leu305
310 315 320 Phe Val Thr Asn Thr
Glu Ile Leu Ser Lys Gly Ile Glu Gln Gly Ile 325
330 335 Gly Asn Ser Ile Leu Ile Lys Val Asn Gln
Ile Gly Thr Leu Thr Glu 340 345
350 Thr Phe Asp Ala Ile Glu Met Ala Gln Lys Ala Gly Tyr Thr Ala
Val 355 360 365 Val
Ser His Arg Ser Gly Glu Thr Glu Asp Thr Thr Ile Ala Asp Ile 370
375 380 Ala Val Ala Thr Asn Ala
Gly Gln Ile Lys Thr Gly Ser Leu Ser Arg385 390
395 400 Thr Asp Arg Ile Ala Lys Tyr Asn Gln Leu Leu
Arg Ile Glu Asp Glu 405 410
415 Leu Tyr Glu Thr Ala Lys Phe Glu Gly Ile Lys Ser Phe Tyr Asn Leu
420 425 430 Asp
Lys5255PRTStaphylococcus sp. 5Met Lys Lys Ile Val Thr Ala Thr Ile Ala Thr
Ala Gly Leu Ala Thr1 5 10
15 Ile Ala Phe Ala Gly His Asp Ala Gln Ala Ala Glu Gln Asn Asn Asn
20 25 30 Gly Tyr Asn
Ser Asn Asp Ala Gln Ser Tyr Ser Tyr Thr Tyr Thr Ile 35
40 45 Asp Ala Gln Gly Asn Tyr His Tyr
Thr Trp Thr Gly Asn Trp Asn Pro 50 55
60 Ser Gln Leu Thr Gln Asn Asn Thr Tyr Tyr Tyr Asn Asn
Tyr Asn Thr65 70 75 80
Tyr Ser Tyr Asn Asn Ala Ser Tyr Asn Asn Tyr Tyr Asn His Ser Tyr
85 90 95 Gln Tyr Asn Asn Tyr
Thr Asn Asn Ser Gln Thr Ala Thr Asn Asn Tyr 100
105 110 Tyr Thr Gly Gly Ser Gly Ala Ser Tyr Ser
Thr Thr Ser Asn Asn Val 115 120
125 His Val Thr Thr Thr Ala Ala Pro Ser Ser Asn Gly Arg Ser
Ile Ser 130 135 140
Asn Gly Tyr Ala Ser Gly Ser Asn Leu Tyr Thr Ser Gly Gln Cys Thr145
150 155 160 Tyr Tyr Val Phe Asp
Arg Val Gly Gly Lys Ile Gly Ser Thr Trp Gly 165
170 175 Asn Ala Ser Asn Trp Ala Asn Ala Ala Ala
Ser Ser Gly Tyr Thr Val 180 185
190 Asn Asn Thr Pro Lys Val Gly Ala Ile Met Gln Thr Thr Gln Gly
Tyr 195 200 205 Tyr
Gly His Val Ala Tyr Val Glu Gly Val Asn Ser Asn Gly Ser Val 210
215 220 Arg Val Ser Glu Met Asn
Tyr Gly His Gly Ala Gly Val Val Thr Ser225 230
235 240 Arg Thr Ile Ser Ala Asn Gln Ala Gly Ser Tyr
Asn Phe Ile His 245 250
255 6267PRTStaphylococcus sp. 6 Met Lys Lys Ile Ala Thr Ala Thr Ile Ala
Thr Ala Gly Phe Ala Thr1 5 10
15 Ile Ala Ile Ala Ser Gly Asn Gln Ala His Ala Ser Glu Gln Asp
Asn 20 25 30 Tyr
Gly Tyr Asn Pro Asn Asp Pro Thr Ser Tyr Ser Tyr Thr Tyr Thr 35
40 45 Ile Asp Ala Gln Gly Asn
Tyr His Tyr Thr Trp Lys Gly Asn Trp His 50 55
60 Pro Ser Gln Leu Asn Gln Asp Asn Gly Tyr Tyr
Ser Tyr Tyr Tyr Tyr65 70 75
80 Asn Gly Tyr Asn Asn Tyr Asn Asn Tyr Asn Asn Gly Tyr Ser Tyr Asn
85 90 95 Asn Tyr Ser
Arg Tyr Asn Asn Tyr Ser Asn Asn Asn Gln Ser Tyr Asn 100
105 110 Tyr Asn Asn Tyr Asn Ser Tyr Asn
Thr Asn Ser Tyr Arg Thr Gly Gly 115 120
125 Leu Gly Ala Ser Tyr Ser Thr Ser Ser Asn Asn Val Gln
Val Thr Thr 130 135 140
Thr Met Ala Pro Ser Ser Asn Gly Arg Ser Ile Ser Ser Gly Tyr Thr145
150 155 160 Ser Gly Arg Asn Leu
Tyr Thr Ser Gly Gln Cys Thr Tyr Tyr Val Phe 165
170 175 Asp Arg Val Gly Gly Lys Ile Gly Ser Thr
Trp Gly Asn Ala Ser Asn 180 185
190 Trp Ala Asn Ala Ala Ala Arg Ala Gly Tyr Thr Val Asn Asn Thr
Pro 195 200 205 Lys
Ala Gly Ala Ile Met Gln Thr Thr Gln Gly Ala Tyr Gly His Val 210
215 220 Ala Tyr Val Glu Ser Val
Asn Ser Asn Gly Ser Val Arg Val Ser Glu225 230
235 240 Met Asn Tyr Gly Tyr Gly Pro Gly Val Val Thr
Ser Arg Thr Ile Ser 245 250
255 Ala Ser Gln Ala Ala Gly Tyr Asn Phe Ile His 260
265 7257PRTStaphylococcus sp. 7Met Lys Lys Ile Ala Thr
Ala Thr Ile Ala Thr Ala Gly Ile Ala Thr1 5
10 15 Phe Ala Phe Ala His His Asp Ala Gln Ala Ala
Glu Gln Asn Asn Asp 20 25 30
Gly Tyr Asn Pro Asn Asp Pro Tyr Ser Tyr Ser Tyr Thr Tyr Thr Ile
35 40 45 Asp Ala Glu
Gly Asn Tyr His Tyr Thr Trp Lys Gly Asn Trp Ser Pro 50
55 60 Asp Arg Val Asn Thr Ser Tyr Asn
Tyr Asn Asn Tyr Asn Asn Tyr Asn65 70 75
80 Tyr Tyr Gly Tyr Asn Asn Tyr Ser Asn Tyr Asn Asn Tyr
Ser Asn Tyr 85 90 95
Asn Asn Tyr Asn Asn Tyr Gln Ser Asn Asn Thr Gln Ser Gln Arg Thr
100 105 110 Thr Gln Pro Thr Gly
Gly Leu Gly Ala Ser Tyr Ser Thr Ser Ser Ser 115
120 125 Asn Val His Val Thr Thr Thr Ser Ala
Pro Ser Ser Asn Gly Val Ser 130 135
140 Leu Ser Asn Ala Arg Ser Ala Ser Gly Asn Leu Tyr Thr
Ser Gly Gln145 150 155
160 Cys Thr Tyr Tyr Val Phe Asp Arg Val Gly Gly Lys Ile Gly Ser Thr
165 170 175 Trp Gly Asn Ala
Asn Asn Trp Ala Asn Ala Ala Ala Arg Ser Gly Tyr 180
185 190 Thr Val Asn Asn Ser Pro Ala Lys Gly
Ala Ile Leu Gln Thr Ser Gln 195 200
205 Gly Ala Tyr Gly His Val Ala Tyr Val Glu Gly Val Asn Ser
Asn Gly 210 215 220
Ser Ile Arg Val Ser Glu Met Asn Tyr Gly His Gly Ala Gly Val Val225
230 235 240 Thr Ser Arg Thr Ile
Ser Ala Ser Gln Ala Ala Ser Tyr Asn Tyr Ile 245
250 255 His8309PRTStaphylococcus sp. 8Met Lys
Lys Leu Val Pro Leu Leu Leu Ala Leu Leu Leu Leu Val Ala1 5
10 15 Ala Cys Gly Thr Gly Gly Lys
Gln Ser Ser Asp Lys Ser Asn Gly Lys 20 25
30 Leu Lys Val Val Thr Thr Asn Ser Ile Leu Tyr Asp
Met Ala Lys Asn 35 40 45
Val Gly Gly Asp Asn Val Asp Ile His Ser Ile Val Pro Val Gly Gln
50 55 60 Asp Pro His
Glu Tyr Glu Val Lys Pro Lys Asp Ile Lys Lys Leu Thr65 70
75 80 Asp Ala Asp Val Ile Leu Tyr Asn
Gly Leu Asn Leu Glu Thr Gly Asn 85 90
95 Gly Trp Phe Glu Lys Ala Leu Glu Gln Ala Gly Lys Ser
Leu Lys Asp 100 105 110
Lys Lys Val Ile Ala Val Ser Lys Asp Val Lys Pro Ile Tyr Leu Asn
115 120 125 Gly Glu Glu Gly
Asn Lys Asp Lys Gln Asp Pro His Ala Trp Leu Ser 130
135 140 Leu Asp Asn Gly Ile Lys Tyr Val
Lys Thr Ile Gln Gln Thr Phe Ile145 150
155 160 Asp Asn Asp Lys Lys His Lys Ala Asp Tyr Glu Lys
Gln Gly Asn Lys 165 170
175 Tyr Ile Ala Gln Leu Glu Lys Leu Asn Asn Asp Ser Lys Asp Lys Phe
180 185 190 Asn Asp Ile
Pro Lys Glu Gln Arg Ala Met Ile Thr Ser Glu Gly Ala 195
200 205 Phe Lys Tyr Phe Ser Lys Gln Tyr
Gly Ile Thr Pro Gly Tyr Ile Trp 210 215
220 Glu Ile Asn Thr Glu Lys Gln Gly Thr Pro Glu Gln Met
Arg Gln Ala225 230 235
240 Ile Glu Phe Val Lys Lys His Lys Leu Lys His Leu Leu Val Glu Thr
245 250 255 Ser Val Asp Lys
Lys Ala Met Glu Ser Leu Ser Glu Glu Thr Lys Lys 260
265 270 Asp Ile Phe Gly Glu Val Tyr Thr Asp
Ser Ile Gly Lys Glu Gly Thr 275 280
285 Lys Gly Asp Ser Tyr Tyr Lys Met Met Lys Ser Asn Ile Glu
Thr Val 290 295 300
His Gly Ser Met Lys305 9309PRTStaphylococcus sp. 9Met Lys
Lys Ile Leu Ala Leu Ala Ile Ala Phe Leu Ile Ile Leu Ala1 5
10 15 Ala Cys Gly Asn His Ser Asn
His Glu His His Ser His Glu Gly Lys 20 25
30 Leu Lys Val Val Thr Thr Asn Ser Ile Leu Tyr Asp
Met Val Lys Arg 35 40 45
Val Gly Gly Asn Lys Val Asp Val His Ser Ile Val Pro Val Gly Gln
50 55 60 Asp Pro His
Glu Tyr Glu Val Lys Pro Lys Asp Ile Lys Ala Leu Thr65 70
75 80 Asp Ala Asp Val Val Phe Tyr Asn
Gly Leu Asn Leu Glu Thr Gly Asn 85 90
95 Gly Trp Phe Glu Lys Ala Leu Asp Gln Ala Gly Lys Ser
Thr Lys Asp 100 105 110
Lys Asn Val Ile Ala Ala Ser Asn Asn Val Lys Pro Ile Tyr Leu Asn
115 120 125 Gly Glu Glu Gly
Asn Lys Asn Lys Gln Asp Pro His Ala Trp Leu Ser 130
135 140 Leu Glu Asn Gly Ile Lys Tyr Val
Lys Thr Ile Gln Lys Ser Leu Glu145 150
155 160 His His Asp Lys Lys Asp Lys Ser Thr Tyr Glu Lys
Gln Gly Asn Ala 165 170
175 Tyr Ile Ser Lys Leu Glu Glu Leu Asn Lys Asp Ser Lys Asn Lys Phe
180 185 190 Asp Asp Ile
Pro Lys Asn Gln Arg Ala Met Met Thr Ser Glu Gly Ala 195
200 205 Phe Lys Tyr Phe Ala Gln Gln Phe
Asp Val Lys Pro Gly Tyr Ile Trp 210 215
220 Glu Ile Asn Thr Glu Lys Gln Gly Thr Pro Gly Gln Met
Lys Gln Ala225 230 235
240 Ile Lys Phe Val Lys Asp Asn His Leu Lys His Leu Leu Val Glu Thr
245 250 255 Ser Val Asp Lys
Lys Ala Met Gln Ser Leu Ser Glu Glu Thr Lys Lys 260
265 270 Asp Ile Tyr Gly Glu Val Phe Thr Asp
Ser Ile Gly Lys Glu Gly Thr 275 280
285 Lys Gly Asp Ser Tyr Tyr Lys Met Met Lys Ser Asn Ile Asp
Thr Ile 290 295 300
His Gly Ser Met Lys305 10233PRTStaphylococcus sp. 10Met
Lys Lys Thr Ile Met Ala Ser Ser Leu Ala Val Ala Leu Gly Val1
5 10 15 Thr Gly Tyr Ala Ala Gly
Thr Gly His Gln Ala His Ala Ala Glu Val 20 25
30 Asn Val Asp Gln Ala His Leu Val Asp Leu Ala
His Asn His Gln Asp 35 40 45
Gln Leu Asn Ala Ala Pro Ile Lys Asp Gly Ala Tyr Asp Ile His Phe
50 55 60 Val Lys Asp
Gly Phe Gln Tyr Asn Phe Thr Ser Asn Gly Thr Thr Trp65 70
75 80 Ser Trp Ser Tyr Glu Ala Ala Asn
Gly Gln Thr Ala Gly Phe Ser Asn 85 90
95 Val Ala Gly Ala Asp Tyr Thr Thr Ser Tyr Asn Gln Gly
Ser Asp Val 100 105 110
Gln Ser Val Ser Tyr Asn Ala Gln Ser Ser Asn Ser Asn Val Glu Ala
115 120 125 Val Ser Ala Pro
Thr Tyr His Asn Tyr Ser Thr Ser Thr Thr Ser Ser 130
135 140 Ser Val Arg Leu Ser Asn Gly Asn
Thr Ala Gly Ala Thr Gly Ser Ser145 150
155 160 Ala Ala Gln Ile Met Ala Gln Arg Thr Gly Val Ser
Ala Ser Thr Trp 165 170
175 Ala Ala Ile Ile Ala Arg Glu Ser Asn Gly Gln Val Asn Ala Tyr Asn
180 185 190 Pro Ser Gly
Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly Pro 195
200 205 Thr Asn Thr Val Asp Gln Gln Ile
Asn Ala Ala Val Lys Ala Tyr Lys 210 215
220 Ala Gln Gly Leu Gly Ala Trp Gly Phe225
230 11235PRTStaphylococcus sp. 11Met Lys Lys Thr Val Ile
Ala Ser Thr Leu Ala Val Ser Leu Gly Ile1 5
10 15 Ala Gly Tyr Gly Leu Ser Gly His Glu Ala His
Ala Ser Glu Thr Thr 20 25 30
Asn Val Asp Lys Ala His Leu Val Asp Leu Ala Gln His Asn Pro Glu
35 40 45 Glu Leu Asn
Ala Lys Pro Val Gln Ala Gly Ala Tyr Asp Ile His Phe 50
55 60 Val Asp Asn Gly Tyr Gln Tyr Asn
Phe Thr Ser Asn Gly Ser Glu Trp65 70 75
80 Ser Trp Ser Tyr Ala Val Ala Gly Ser Asp Ala Asp Tyr
Thr Glu Ser 85 90 95
Ser Ser Asn Gln Glu Val Ser Ala Asn Thr Gln Ser Ser Asn Thr Asn
100 105 110 Val Gln Ala Val Ser
Ala Pro Thr Ser Ser Glu Ser Arg Ser Tyr Ser 115
120 125 Thr Ser Thr Thr Ser Tyr Ser Ala Pro
Ser His Asn Tyr Ser Ser His 130 135
140 Ser Ser Ser Val Arg Leu Ser Asn Gly Asn Thr Ala Gly
Ser Val Gly145 150 155
160 Ser Tyr Ala Ala Ala Gln Met Ala Ala Arg Thr Gly Val Ser Ala Ser
165 170 175 Thr Trp Glu His
Ile Ile Ala Arg Glu Ser Asn Gly Gln Leu His Ala 180
185 190 Arg Asn Ala Ser Gly Ala Ala Gly Leu
Phe Gln Thr Met Pro Gly Trp 195 200
205 Gly Ser Thr Gly Ser Val Asn Asp Gln Ile Asn Ala Ala Tyr
Lys Ala 210 215 220
Tyr Lys Ala Gln Gly Leu Ser Ala Trp Gly Met225 230
235 123890PRTStaphylococcus sp. 12Met Asn Tyr Arg Asp Lys Ile
Gln Lys Phe Ser Ile Arg Lys Tyr Thr1 5 10
15 Val Gly Thr Phe Ser Thr Val Ile Ala Thr Leu Val
Phe Leu Gly Phe 20 25 30
Asn Thr Ser Gln Ala His Ala Ala Glu Thr Asn Gln Pro Ala Ser Val
35 40 45 Val Lys Gln Lys
Gln Gln Ser Asn Asn Glu Gln Thr Glu Asn Arg Glu 50 55
60 Ser Gln Val Gln Asn Ser Gln Asn Ser
Gln Asn Ser Gln Ser Leu Ser65 70 75
80 Ala Thr His Glu Asn Glu Gln Pro Asn Asn Ser Gln Ala Asn
Leu Val 85 90 95
Asn Gln Lys Val Ala Gln Ser Ser Thr Thr Asn Asp Glu Gln Pro Ala
100 105 110 Ser Gln Asn Val Asn
Thr Lys Lys Asp Ser Ala Thr Ala Ala Thr Thr 115
120 125 Gln Pro Asp Lys Glu Glu Ser Lys His
Lys Gln Asn Glu Ser Gln Ser 130 135
140 Ala Asn Lys Asn Gly Asn Asp Asn Arg Ala Ala His Val
Glu Asn His145 150 155
160 Glu Ala Asn Val Val Thr Ala Ser Asp Ser Ser Asp Asn Gly Asn Val
165 170 175 Gln His Asp Arg
Asn Glu Leu Gln Ala Phe Phe Asp Ala Asn Tyr His 180
185 190 Asp Tyr Arg Phe Ile Asp Arg Glu Asn
Ala Asp Ser Gly Thr Phe Asn 195 200
205 Tyr Val Lys Gly Ile Phe Asp Lys Ile Asn Thr Leu Leu Gly
Ser Asn 210 215 220
Asp Pro Ile Asn Asn Lys Asp Leu Gln Leu Ala Tyr Lys Glu Leu Glu225
230 235 240 Gln Ala Val Ala Leu
Ile Arg Thr Met Pro Gln Arg Gln Gln Thr Ser 245
250 255 Arg Arg Ser Asn Arg Ile Gln Thr Arg Ser
Val Glu Ser Arg Ala Ala 260 265
270 Glu Pro Arg Ser Val Ser Asp Tyr Gln Asn Ala Asn Ser Ser Tyr
Tyr 275 280 285 Val
Glu Asn Ala Asn Asp Gly Ser Gly Tyr Pro Val Gly Thr Tyr Ile 290
295 300 Asn Ala Ser Ser Lys Gly
Ala Pro Tyr Asn Leu Pro Thr Thr Pro Trp305 310
315 320 Asn Thr Leu Lys Ala Ser Asp Ser Lys Glu Ile
Ala Leu Met Thr Ala 325 330
335 Lys Gln Thr Gly Asp Gly Tyr Gln Trp Val Ile Lys Phe Asn Lys Gly
340 345 350 His Ala Pro
His Gln Asn Met Ile Phe Trp Phe Ala Leu Pro Ala Asp 355
360 365 Gln Val Pro Val Gly Arg Thr Asp
Phe Val Thr Val Asn Ser Asp Gly 370 375
380 Thr Asn Val Gln Trp Ser His Gly Ala Gly Ala Gly Ala
Asn Lys Pro385 390 395
400 Leu Gln Gln Met Trp Glu Tyr Gly Val Asn Asp Pro Asp Arg Ser His
405 410 415 Asp Phe Lys Ile
Arg Asn Arg Ser Gly Gln Val Ile Tyr Ser Trp Pro 420
425 430 Thr Val His Val Tyr Ser Leu Glu Asp
Leu Ser Arg Ala Ser Asp Tyr 435 440
445 Phe Ser Glu Ala Gly Ala Thr Pro Ala Thr Lys Ala Phe Gly
Arg Gln 450 455 460
Asn Phe Glu Tyr Ile Asn Gly Gln Lys Pro Ala Glu Ser Pro Gly Val465
470 475 480 Pro Lys Val Tyr Thr
Phe Ile Gly Gln Gly Asp Ala Ser Tyr Thr Ile 485
490 495 Ser Phe Lys Thr Gln Gly Pro Thr Val Asn
Lys Leu Tyr Tyr Ala Ala 500 505
510 Gly Gly Arg Ala Leu Glu Tyr Asn Gln Leu Phe Met Tyr Ser Gln
Leu 515 520 525 Tyr
Val Glu Ser Thr Gln Asp His Gln Gln Arg Leu Asn Gly Leu Arg 530
535 540 Gln Val Val Asn Arg Thr
Tyr Arg Ile Gly Thr Thr Lys Arg Val Glu545 550
555 560 Val Ser Gln Gly Asn Val Gln Thr Lys Lys Val
Leu Glu Ser Thr Asn 565 570
575 Leu Asn Ile Asp Asp Phe Val Asp Asp Pro Leu Ser Tyr Val Lys Thr
580 585 590 Pro Ser Asn
Lys Val Leu Gly Phe Tyr Pro Thr Asn Ala Asn Thr Asn 595
600 605 Ala Phe Arg Pro Gly Gly Val Gln
Glu Leu Asn Glu Tyr Gln Leu Ser 610 615
620 Gln Leu Phe Thr Asp Gln Lys Leu Gln Glu Ala Ala Arg
Thr Arg Asn625 630 635
640 Pro Ile Arg Leu Met Ile Gly Phe Asp Tyr Pro Asp Gly Tyr Gly Asn
645 650 655 Ser Glu Thr Leu
Val Pro Val Asn Leu Thr Val Leu Pro Glu Ile Gln 660
665 670 His Asn Ile Lys Phe Phe Lys Asn Asp
Asp Thr Gln Asn Ile Ala Glu 675 680
685 Lys Pro Phe Ser Lys Gln Ala Gly His Pro Val Phe Tyr Val
Tyr Ala 690 695 700
Gly Asn Gln Gly Asn Ala Ser Val Asn Leu Gly Gly Ser Val Thr Ser705
710 715 720 Ile Gln Pro Leu Arg
Ile Asn Leu Thr Ser Asn Glu Asn Phe Thr Asp 725
730 735 Lys Asp Trp Gln Ile Thr Gly Ile Pro Arg
Thr Leu His Ile Glu Asn 740 745
750 Ser Thr Asn Arg Thr Asn Asn Ala Arg Glu Arg Asn Ile Glu Leu
Val 755 760 765 Gly
Asn Leu Leu Pro Gly Asp Tyr Phe Gly Thr Ile Arg Phe Gly Arg 770
775 780 Lys Glu Gln Leu Phe Glu
Ile Arg Val Lys Pro His Thr Pro Thr Ile785 790
795 800 Thr Thr Thr Ala Glu Gln Leu Arg Gly Thr Ala
Leu Gln Lys Val Pro 805 810
815 Val Asn Ile Ser Gly Ile Pro Leu Asp Pro Ser Ala Leu Val Tyr Leu
820 825 830 Val Ala Pro
Thr Asn Gln Thr Thr Asn Gly Gly Ser Glu Ala Asp Gln 835
840 845 Ile Pro Ser Gly Tyr Thr Ile Leu
Ala Thr Gly Thr Pro Asp Gly Val 850 855
860 His Asn Thr Ile Thr Ile Arg Pro Gln Asp Tyr Val Val
Phe Ile Pro865 870 875
880 Pro Val Gly Lys Gln Ile Arg Ala Val Val Tyr Tyr Asn Lys Val Val
885 890 895 Ala Ser Asn Met
Ser Asn Ala Val Thr Ile Leu Pro Asp Asp Ile Pro 900
905 910 Pro Thr Ile Asn Asn Pro Val Gly Ile
Asn Ala Lys Tyr Tyr Arg Gly 915 920
925 Asp Glu Val Asn Phe Thr Met Gly Val Ser Asp Arg His Ser
Gly Ile 930 935 940
Lys Asn Thr Thr Ile Thr Thr Leu Pro Ser Gly Trp Thr Ser Asn Leu945
950 955 960 Thr Lys Ser Asp Asn
Lys Asn Gly Ser Leu Ala Ile Thr Gly Arg Val 965
970 975 Ser Met Asn Gln Ala Phe Asn Ser Asp Ile
Thr Phe Lys Val Ser Ala 980 985
990 Thr Asp Asn Val Asn Asn Thr Thr Asn Asp Ser Gln Ser Lys His
Val 995 1000 1005 Ser
Ile His Val Gly Lys Ile Ser Glu Asp Ala His Pro Ile Val Leu 1010
1015 1020 Gly Asn Thr Glu Lys Val
Val Val Val Asn Pro Thr Ala Val Ser Asn1025 1030
1035 1040Asp Glu Lys Gln Ser Ile Ile Thr Ala Phe Met
Asn Lys Asn Gln Asn 1045 1050
1055 Ile Arg Gly Tyr Leu Ala Ser Thr Asp Pro Val Thr Val Asp Asn Asn
1060 1065 1070 Gly Asn Val
Thr Leu His Tyr Arg Asp Gly Ser Ser Thr Thr Leu Asp 1075
1080 1085 Ala Thr Asn Val Met Thr Tyr Glu
Pro Val Val Lys Ser Glu Tyr Gln 1090 1095
1100 Thr Ala Asn Ala Ala Lys Thr Ala Thr Val Thr Ile Ala
Lys Gly Gln1105 1110 1115
1120Ser Phe Asn Ile Gly Asp Ile Lys Gln Tyr Phe Thr Leu Ser Asn Gly
1125 1130 1135 Gln Ala Ile Pro
Asn Gly Thr Phe Thr Asn Ile Thr Ser Asp Arg Thr 1140
1145 1150 Ile Pro Thr Ala Gln Glu Val Ser Gln
Met Asn Ala Gly Thr Gln Leu 1155 1160
1165 Tyr His Ile Val Ala Ser Asn Ala Tyr His Lys Asp Thr Glu
Asp Phe 1170 1175 1180
Tyr Ile Ser Leu Lys Ile Val Asp Val Lys Gln Pro Glu Gly Asp Gln1185
1190 1195 1200Arg Val Tyr Arg Thr
Ser Thr Tyr Asp Leu Thr Thr Asp Glu Ile Ser 1205
1210 1215 Lys Val Lys Gln Ala Phe Ile Asn Ala Asn
Arg Asp Val Ile Thr Leu 1220 1225
1230 Ala Glu Gly Asp Ile Ser Val Thr Asn Thr Pro Asn Gly Ala Asn
Val 1235 1240 1245 Ser
Thr Ile Thr Val Asn Ile Asn Lys Gly Arg Leu Thr Lys Ser Phe 1250
1255 1260 Ala Ser Asn Leu Ala Asn
Met Asn Phe Leu Arg Trp Val Asn Phe Pro1265 1270
1275 1280Gln Asp Tyr Thr Val Thr Trp Thr Asn Ala Lys
Ile Ala Asn Arg Pro 1285 1290
1295 Thr Asp Gly Gly Leu Ser Trp Ser Asp Asp His Lys Ser Leu Ile Tyr
1300 1305 1310 Arg Tyr Asp
Ala Thr Leu Gly Thr Gln Ile Thr Thr Asn Asp Ile Leu 1315
1320 1325 Thr Met Leu Lys Ala Thr Thr Thr
Val Pro Gly Leu Arg Asn Asn Ile 1330 1335
1340 Thr Gly Asn Glu Lys Ala Gln Ala Glu Ala Gly Gly Arg
Pro Asn Tyr1345 1350 1355
1360Arg Thr Thr Gly Tyr Ser Gln Ser Asn Ala Thr Thr Asp Gly Gln Arg
1365 1370 1375 Gln Phe Thr Leu
Asn Gly Gln Val Ile Gln Ile Leu Asp Ile Ile Asn 1380
1385 1390 Pro Ser Asn Gly Tyr Gly Gly Gln Pro
Val Thr Asn Ser Asn Thr Arg 1395 1400
1405 Ala Asn His Ser Asn Ser Thr Val Val Asn Val Asn Glu Pro
Ala Ala 1410 1415 1420
Asn Gly Ala Gly Ala Phe Thr Ile Asp His Val Val Lys Ser Asn Ser1425
1430 1435 1440Thr His Asn Ala Ser
Asp Ala Val Tyr Lys Ala Gln Leu Tyr Leu Thr 1445
1450 1455 Pro Tyr Gly Pro Lys Gln Tyr Val Glu His
Leu Asn Gln Asn Thr Gly 1460 1465
1470 Asn Thr Thr Asp Ala Ile Asn Ile Tyr Phe Val Pro Ser Asp Leu
Val 1475 1480 1485 Asn
Pro Thr Ile Ser Val Gly Asn Tyr Thr Asn His Gln Val Phe Ser 1490
1495 1500 Gly Glu Thr Phe Thr Asn
Thr Ile Thr Ala Asn Asp Asn Phe Gly Val1505 1510
1515 1520Gln Ser Val Thr Val Pro Asn Thr Ser Gln Ile
Thr Gly Thr Val Asp 1525 1530
1535 Asn Asn His Gln His Val Ser Ala Thr Ala Pro Asn Val Thr Ser Ala
1540 1545 1550 Thr Ser Lys
Thr Ile Asn Leu Leu Ala Thr Asp Thr Ser Gly Asn Thr 1555
1560 1565 Ala Thr Thr Ser Phe Asn Val Thr
Val Lys Pro Leu Arg Asp Lys Tyr 1570 1575
1580 Arg Val Gly Thr Ser Ser Thr Ala Ala Asn Pro Val Arg
Ile Ala Asn1585 1590 1595
1600Ile Ser Asn Asn Ala Thr Val Ser Gln Ala Asp Gln Thr Thr Ile Ile
1605 1610 1615 Asn Ser Leu Thr
Phe Thr Ser Asn Ala Pro Asn Arg Asn Tyr Ala Thr 1620
1625 1630 Ala Ser Ala Asn Glu Ile Thr Ser Lys
Thr Val Ser Asn Val Ser Arg 1635 1640
1645 Thr Gly Asn Asn Ala Asn Val Thr Val Thr Val Thr His Gln
Asp Gly 1650 1655 1660
Thr Thr Ser Thr Val Thr Val Pro Val Lys His Val Ile Pro Glu Ile1665
1670 1675 1680Val Ala His Ser His
Tyr Thr Val Gln Gly Gln Asp Phe Pro Ala Gly 1685
1690 1695 Asn Gly Ser Ser Ala Ala Asp Tyr Phe Lys
Leu Ser Asn Gly Ser Ala 1700 1705
1710 Ile Pro Asp Ala Thr Ile Thr Trp Val Ser Gly Gln Ala Pro Asn
Lys 1715 1720 1725 Asp
Asn Thr Arg Ile Gly Glu Asp Ile Thr Val Thr Ala His Ile Leu 1730
1735 1740 Ile Asp Gly Glu Thr Thr
Pro Ile Thr Lys Thr Ala Thr Tyr Lys Val1745 1750
1755 1760Val Arg Thr Val Pro Lys His Val Phe Glu Thr
Ala Arg Gly Val Leu 1765 1770
1775 Tyr Pro Gly Val Ser Asp Met Tyr Asp Ala Lys Gln Tyr Val Lys Pro
1780 1785 1790 Val Asn Asn
Ser Trp Ser Thr Asn Ala Gln His Met Asn Phe Gln Phe 1795
1800 1805 Val Gly Thr Tyr Gly Pro Asn Lys
Asp Val Val Gly Ile Ser Thr Arg 1810 1815
1820 Leu Ile Arg Val Thr Tyr Asp Asn Arg Gln Thr Glu Asp
Leu Thr Ile1825 1830 1835
1840Leu Ser Lys Val Lys Pro Asp Pro Pro Arg Ile Asp Ala Asn Ser Val
1845 1850 1855 Thr Tyr Lys Ala
Gly Leu Thr Asn Gln Glu Ile Lys Val Asn Asn Val 1860
1865 1870 Leu Asn Asn Ser Ser Val Lys Leu Phe
Lys Ala Asp Asn Thr Pro Leu 1875 1880
1885 Asn Val Thr Asn Ile Thr His Gly Ser Gly Phe Ser Ser Val
Val Thr 1890 1895 1900
Val Ser Asp Ala Leu Pro Asn Gly Gly Ile Lys Ala Lys Ser Ser Ile1905
1910 1915 1920Ser Met Asn Asn Val
Thr Tyr Thr Thr Gln Asp Glu His Gly Gln Val 1925
1930 1935 Val Thr Val Thr Arg Asn Glu Ser Val Asp
Ser Asn Asp Ser Ala Ser 1940 1945
1950 Val Thr Val Thr Pro Gln Leu Gln Ala Thr Thr Glu Gly Ala Val
Phe 1955 1960 1965 Ile
Lys Gly Gly Asp Gly Phe Asp Phe Gly His Val Glu Arg Phe Ile 1970
1975 1980 Gln Asn Pro Pro His Gly
Ala Thr Val Ala Trp His Asp Ser Pro Asp1985 1990
1995 2000Thr Trp Lys Asn Thr Val Gly Asn Thr His Lys
Thr Ala Val Val Thr 2005 2010
2015 Leu Pro Ser Gly Gln Gly Thr Arg Asn Val Glu Val Pro Val Lys Val
2020 2025 2030 Tyr Pro Val
Ala Asn Ala Lys Ala Pro Ser Arg Asp Val Lys Gly Gln 2035
2040 2045 Asn Leu Thr His Gly Thr Asn Ala
Ile Asp Tyr Ile Thr Phe Asp Pro 2050 2055
2060 Asn Thr Asn Thr Asn Gly Ile Thr Ala Ala Trp Ala Asn
Arg Gln Gln2065 2070 2075
2080Pro Asn Asn Gln Gln Ala Gly Val Gln His Leu Asn Val Asp Val Thr
2085 2090 2095 Tyr Pro Gly Ile
Ser Ala Ala Lys Arg Val Pro Val Thr Val Asn Val 2100
2105 2110 Tyr Gln Phe Glu Phe Pro Gln Thr Thr
Tyr Thr Thr Thr Val Gly Gly 2115 2120
2125 Thr Leu Ala Ser Gly Thr Gln Ala Ser Gly Tyr Ala His Met
Gln Asn 2130 2135 2140
Ala Ser Gly Leu Pro Thr Asp Gly Phe Thr Tyr Lys Trp Asn Arg Asp2145
2150 2155 2160Thr Thr Gly Thr Asn
Asp Ala Asn Trp Ala Ala Met Asn Lys Pro Asn 2165
2170 2175 Thr Ala Gln Val Val Asn Ala Lys Tyr Asp
Val Ile Tyr Asn Gly His 2180 2185
2190 Thr Phe Ala Thr Ser Leu Pro Ala Lys Phe Val Val Lys Asp Val
Gln 2195 2200 2205 Pro
Ala Lys Pro Thr Val Thr Glu Thr Ala Ala Gly Ala Ile Thr Ile 2210
2215 2220 Ala Pro Gly Ala Asn Gln
Thr Val Asn Thr His Ala Gly Asn Val Thr2225 2230
2235 2240Thr Tyr Ala Asp Lys Leu Val Ile Lys Arg Asn
Gly Asn Val Val Thr 2245 2250
2255 Thr Phe Thr Arg Arg Asn Asn Thr Ser Pro Trp Val Lys Glu Ala Ser
2260 2265 2270 Ala Asp Asn
Val Thr Gly Ile Val Gly Thr Asn Asn Gly Ile Thr Val 2275
2280 2285 Ala Ala Gly Thr Phe Asn Pro Ala
Asp Thr Ile Gln Val Val Ala Thr 2290 2295
2300 Gln Gly Ser Gly Glu Thr Ile Ser Asp Glu Gln Arg Ser
Asp Asp Phe2305 2310 2315
2320Thr Val Val Ala Pro Gln Pro Asn Gln Ala Thr Thr Lys Ile Trp Gln
2325 2330 2335 Asn Gly His Ile
Asp Ile Thr Pro Asn Asn Pro Ser Gly His Leu Ile 2340
2345 2350 Asn Pro Thr Gln Ala Met Asp Ile Ala
Tyr Thr Glu Lys Val Gly Asn 2355 2360
2365 Gly Ala Glu His Ser Lys Thr Ile Asn Val Val Arg Gly Gln
Asn Asn 2370 2375 2380
Gln Trp Thr Ile Ala Asn Lys Pro Asp Tyr Val Thr Leu Asp Ala Gln2385
2390 2395 2400Thr Gly Lys Val Thr
Phe Asn Ala Asn Thr Ile Lys Pro Asn Ser Ser 2405
2410 2415 Ile Thr Ile Thr Pro Lys Ala Gly Thr Gly
His Ser Val Ser Ser Asn 2420 2425
2430 Pro Ser Thr Leu Thr Ala Pro Ala Ala His Thr Val Asn Thr Thr
Glu 2435 2440 2445 Ile
Val Lys Asp Tyr Gly Ser Asn Val Thr Ala Ala Glu Ile Asn Asn 2450
2455 2460 Ala Val Gln Val Ala Asn
Lys Arg Thr Ala Thr Ile Lys Asn Gly Thr2465 2470
2475 2480Ala Met Pro Thr Asn Leu Ala Gly Gly Ser Thr
Thr Thr Ile Pro Val 2485 2490
2495 Thr Val Thr Tyr Asn Asp Gly Ser Thr Glu Glu Val Gln Glu Ser Ile
2500 2505 2510 Phe Thr Lys
Ala Asp Lys Arg Glu Leu Ile Thr Ala Lys Asn His Leu 2515
2520 2525 Asp Asp Pro Val Ser Thr Glu Gly
Lys Lys Pro Gly Thr Ile Thr Gln 2530 2535
2540 Tyr Asn Asn Ala Met His Asn Ala Gln Gln Gln Ile Asn
Thr Ala Lys2545 2550 2555
2560Thr Glu Ala Gln Gln Val Ile Asn Asn Glu Arg Ala Thr Pro Gln Gln
2565 2570 2575 Val Ser Asp Ala
Leu Thr Lys Val Arg Ala Ala Gln Thr Lys Ile Asp 2580
2585 2590 Gln Ala Lys Ala Leu Leu Gln Asn Lys
Glu Asp Asn Ser Gln Leu Val 2595 2600
2605 Thr Ser Lys Asn Asn Leu Gln Ser Ser Val Asn Gln Val Pro
Ser Thr 2610 2615 2620
Ala Gly Met Thr Gln Gln Ser Ile Asp Asn Tyr Asn Ala Lys Lys Arg2625
2630 2635 2640Glu Ala Glu Thr Glu
Ile Thr Ala Ala Gln Arg Val Ile Asp Asn Gly 2645
2650 2655 Asp Ala Thr Ala Gln Gln Ile Ser Asp Glu
Lys His Arg Val Asp Asn 2660 2665
2670 Ala Leu Thr Ala Leu Asn Gln Ala Lys His Asp Leu Thr Ala Asp
Thr 2675 2680 2685 His
Ala Leu Glu Gln Ala Val Gln Gln Leu Asn Arg Thr Gly Thr Thr 2690
2695 2700 Thr Gly Lys Lys Pro Ala
Ser Ile Thr Ala Tyr Asn Asn Ser Ile Arg2705 2710
2715 2720Ala Leu Gln Ser Asp Leu Thr Ser Ala Lys Asn
Ser Ala Asn Ala Ile 2725 2730
2735 Ile Gln Lys Pro Ile Arg Thr Val Gln Glu Val Gln Ser Ala Leu Thr
2740 2745 2750 Asn Val Asn
Arg Val Asn Glu Arg Leu Thr Gln Ala Ile Asn Gln Leu 2755
2760 2765 Val Pro Leu Ala Asp Asn Ser Ala
Leu Arg Thr Ala Lys Thr Lys Leu 2770 2775
2780 Asp Glu Glu Ile Asn Lys Ser Val Thr Thr Asp Gly Met
Thr Gln Ser2785 2790 2795
2800Ser Ile Gln Ala Tyr Glu Asn Ala Lys Arg Ala Gly Gln Thr Glu Thr
2805 2810 2815 Thr Asn Ala Gln
Asn Val Ile Asn Asn Gly Asp Ala Thr Asp Gln Gln 2820
2825 2830 Ile Ala Ala Glu Lys Thr Lys Val Glu
Glu Lys Tyr Asn Ser Leu Lys 2835 2840
2845 Gln Ala Ile Ala Gly Leu Thr Pro Asp Leu Ala Pro Leu Gln
Thr Ala 2850 2855 2860
Lys Thr Gln Leu Gln Asn Asp Ile Asp Gln Pro Thr Ser Thr Thr Gly2865
2870 2875 2880Met Thr Ser Ala Ser
Val Ala Ala Phe Asn Asp Lys Leu Ser Ala Ala 2885
2890 2895 Arg Thr Lys Ile Gln Glu Ile Asp Arg Val
Leu Ala Ser His Pro Asp 2900 2905
2910 Val Ala Thr Ile Arg Gln Asn Val Thr Ala Ala Asn Ala Ala Lys
Thr 2915 2920 2925 Ala
Leu Asp Gln Ala Arg Asn Gly Leu Thr Val Asp Lys Ala Pro Leu 2930
2935 2940 Glu Asn Ala Lys Asn Gln
Leu Gln His Ser Ile Asp Thr Gln Thr Ser2945 2950
2955 2960Thr Thr Gly Met Thr Gln Asp Ser Ile Asn Ala
Tyr Asn Ala Lys Leu 2965 2970
2975 Thr Ala Ala Arg Asn Lys Val Gln Gln Ile Asn Gln Val Leu Ala Gly
2980 2985 2990 Ser Pro Thr
Val Asp Gln Ile Asn Thr Asn Thr Ser Ala Ala Asn Gln 2995
3000 3005 Ala Lys Ser Asp Leu Asp His Ala
Arg Gln Ala Leu Thr Pro Asp Lys 3010 3015
3020 Ala Pro Leu Gln Asn Ala Lys Thr Gln Leu Glu Gln Ser
Ile Asn Gln3025 3030 3035
3040Pro Thr Asp Thr Thr Gly Met Thr Thr Ala Ser Leu Asn Ala Tyr Asn
3045 3050 3055 Gln Lys Leu Gln
Ala Ala Arg Gln Lys Leu Thr Glu Ile Asn Gln Val 3060
3065 3070 Leu Asn Gly Asn Pro Thr Val Gln Asn
Ile Asn Asp Lys Val Ala Glu 3075 3080
3085 Ala Asn Gln Ala Lys Asp Gln Leu Asn Thr Ala Arg Gln Gly
Leu Thr 3090 3095 3100
Leu Asp Arg Gln Pro Ala Leu Thr Thr Leu His Gly Ala Ser Asn Leu3105
3110 3115 3120Asn Gln Ala Gln Gln
Asn Asn Phe Thr Gln Gln Ile Asn Ala Ala Gln 3125
3130 3135 Asn His Ala Ala Leu Glu Thr Ile Lys Ser
Asn Ile Thr Ala Leu Asn 3140 3145
3150 Thr Ala Met Thr Lys Leu Lys Asp Ser Val Ala Asp Asn Asn Thr
Ile 3155 3160 3165 Lys
Ser Gly Gln Asn Tyr Thr Asp Ala Thr Pro Ala Asn Lys Gln Ala 3170
3175 3180 Tyr Asp Asn Ala Val Asn
Ala Ala Lys Gly Val Ile Gly Glu Thr Thr3185 3190
3195 3200Asn Pro Thr Met Asp Val Asn Thr Val Asn Gln
Lys Ala Ala Ser Val 3205 3210
3215 Lys Ser Thr Lys Asp Ala Leu Asp Gly Gln Gln Asn Leu Gln Arg Ala
3220 3225 3230 Lys Thr Glu
Ala Thr Asn Ala Ile Thr His Ala Ser Asp Leu Asn Gln 3235
3240 3245 Ala Gln Lys Asn Ala Leu Thr Gln
Gln Val Asn Ser Ala Gln Asn Val 3250 3255
3260 Gln Ala Val Asn Asp Ile Lys Gln Thr Thr Gln Ser Leu
Asn Thr Ala3265 3270 3275
3280Met Thr Gly Leu Lys Arg Gly Val Ala Asn His Asn Gln Val Val Gln
3285 3290 3295 Ser Asp Asn Tyr
Val Asn Ala Asp Thr Asn Lys Lys Asn Asp Tyr Asn 3300
3305 3310 Asn Ala Tyr Asn His Ala Asn Asp Ile
Ile Asn Gly Asn Ala Gln His 3315 3320
3325 Pro Val Ile Thr Pro Ser Asp Val Asn Asn Ala Leu Ser Asn
Val Thr 3330 3335 3340
Ser Lys Glu His Ala Leu Asn Gly Glu Ala Lys Leu Asn Ala Ala Lys3345
3350 3355 3360Gln Glu Ala Asn Thr
Ala Leu Gly His Leu Asn Asn Leu Asn Asn Val 3365
3370 3375 Gln Arg Gln Asn Leu Gln Ser Gln Ile Asn
Gly Ala His Gln Ile Asp 3380 3385
3390 Ala Val Asn Thr Ile Lys Gln Asn Ala Thr Asn Leu Asn Ser Ala
Met 3395 3400 3405 Gly
Asn Leu Arg Gln Ala Val Ala Asp Lys Asp Gln Val Lys Arg Thr 3410
3415 3420 Glu Asp Tyr Ala Asp Ala
Asp Thr Ala Lys Gln Asn Ala Tyr Asn Ser3425 3430
3435 3440Ala Val Ser Ser Ala Glu Thr Ile Ile Asn Gln
Thr Ala Asn Pro Thr 3445 3450
3455 Met Ser Val Asp Asp Val Asn Arg Ala Thr Ser Ala Val Thr Thr Asn
3460 3465 3470 Lys Asn Ala
Leu Asn Gly Asp Glu Lys Leu Val Gln Ser Lys Thr Asp 3475
3480 3485 Ala Ala Arg Ala Ile Asp Ala Leu
Pro His Leu Asn Asn Ala Gln Lys 3490 3495
3500 Ala Asp Val Lys Ser Lys Ile Asn Ala Ala Ser Asn Ile
Ala Gly Val3505 3510 3515
3520Asn Thr Val Lys Gln Gln Gly Thr Asp Leu Asn Thr Ala Met Gly Asn
3525 3530 3535 Leu Gln Gly Ala
Ile Asn Asp Glu Gln Thr Thr Leu Asn Ser Gln Asn 3540
3545 3550 Tyr Gln Asp Ala Thr Pro Ser Lys Lys
Thr Ala Tyr Thr Asn Ala Val 3555 3560
3565 Gln Ala Ala Lys Asp Ile Leu Asn Lys Ser Asn Gly Gln Asn
Lys Thr 3570 3575 3580
Lys Asp Gln Val Thr Glu Ala Met Asn Gln Val Asn Ser Ala Lys Asn3585
3590 3595 3600Asn Leu Asp Gly Thr
Arg Leu Leu Asp Gln Ala Lys Gln Thr Ala Lys 3605
3610 3615 Gln Gln Leu Asn Asn Met Thr His Leu Thr
Thr Ala Gln Lys Thr Asn 3620 3625
3630 Leu Thr Asn Gln Ile Asn Ser Gly Thr Thr Val Ala Gly Val His
Thr 3635 3640 3645 Val
Gln Ser Asn Ala Asn Thr Leu Asp Gln Ala Met Asn Thr Leu Arg 3650
3655 3660 Gln Ser Ile Ala Asn Asn
Asp Ala Thr Lys Ala Ser Glu Asp Tyr Val3665 3670
3675 3680Asp Ala Asn Asn Asp Lys Gln Thr Ala Tyr Asn
Asn Ala Val Ala Ala 3685 3690
3695 Ala Glu Thr Ile Ile Asn Ala Asn Ser Asn Pro Glu Met Asn Pro Ser
3700 3705 3710 Thr Ile Thr
Gln Lys Ala Glu Gln Val Asn Ser Ser Lys Thr Ala Leu 3715
3720 3725 Asn Gly Asp Glu Asn Leu Ala Thr
Ala Lys Gln Asn Ala Lys Thr Tyr 3730 3735
3740 Leu Asn Thr Leu Thr Ser Ile Thr Asp Ala Gln Lys Asn
Asn Leu Ile3745 3750 3755
3760Ser Gln Ile Ser Ser Ala Thr Arg Val Ser Gly Val Asp Thr Val Lys
3765 3770 3775 Gln Asn Ala Gln
His Leu Asp Gln Ala Met Ala Asn Leu Gln Asn Gly 3780
3785 3790 Ile Asn Asn Glu Ser Gln Val Lys Ser
Ser Glu Lys Tyr Arg Asp Ala 3795 3800
3805 Asp Thr Asn Lys Gln Gln Glu Tyr Asp Asn Ala Ile Thr Ala
Ala Lys 3810 3815 3820
Ala Ile Leu Asn Lys Ser Thr Gly Pro Asn Thr Ala Gln Asn Ala Val3825
3830 3835 3840Glu Ala Ala Leu Gln
Arg Val Asn Thr Ala Lys Asp Ala Leu Asn Gly 3845
3850 3855 Asp Ala Lys Leu Ile Ala Ala Gln Asn Ala
Ala Lys Gln His Leu Gly 3860 3865
3870 Thr Leu Thr His Ile Thr Thr Ala Gln Arg Asn Asp Leu Thr Asn
Gln 3875 3880 3885 Ile
Ser 3890136713PRTStaphylococcus sp. 13Met Gly Asn Leu Gln Thr Ala Ile
Asn Asp Lys Ser Gly Thr Leu Ala1 5 10
15 Ser Gln Asn Phe Leu Asp Ala Asp Glu Gln Lys Arg Asn
Ala Tyr Asn 20 25 30
Gln Ala Ile Ser Ala Ala Glu Thr Ile Leu Asn Lys Gln Thr Gly Pro
35 40 45 Asn Thr Ala Lys
Thr Ala Val Glu Gln Ala Leu Asn Asn Val Asn Ser 50 55
60 Ala Lys His Ala Leu Asn Gly Thr Gln
Asn Leu Asn Asn Ala Lys Gln65 70 75
80 Ala Ala Ile Thr Ala Ile Asn Gly Ala Ser Asp Leu Asn Gln
Lys Gln 85 90 95
Lys Asp Ala Leu Lys Ala Gln Ala Asn Gly Ala Gln Arg Val Ser Asn
100 105 110 Ala Asn Asp Val Gln
Arg Asn Ala Thr Glu Leu Asn Thr Ala Met Gly 115
120 125 Gln Leu Gln His Ala Ile Ala Asp Lys
Thr Asn Thr Leu Ala Ser Ser 130 135
140 Lys Tyr Val Asn Ala Asp Ser Thr Lys Gln Asn Ala Tyr
Thr Thr Lys145 150 155
160 Val Thr Asn Ala Glu His Ile Ile Ser Gly Thr Pro Thr Val Val Thr
165 170 175 Thr Pro Ser Glu
Val Thr Ala Ala Ala Asn Gln Val Asn Ser Ala Lys 180
185 190 Gln Glu Leu Asn Gly Asp Glu Arg Leu
Arg Val Ala Lys Gln Asn Ala 195 200
205 Asn Thr Ala Ile Asp Ala Leu Thr Gln Leu Asn Thr Pro Gln
Lys Ala 210 215 220
Lys Leu Lys Glu Gln Val Gly Gln Ala Asn Arg Leu Glu Asp Val Gln225
230 235 240 Ser Val Gln Thr Asn
Gly Gln Ser Leu Asn Asn Ala Met Lys Gly Leu 245
250 255 Arg Asp Ser Ile Ala Asn Glu Thr Thr Val
Lys Ala Ser Gln Asn Tyr 260 265
270 Thr Asp Ala Ser Pro Asn Asn Gln Ser Thr Tyr Asn Ser Ala Val
Ser 275 280 285 Asn
Ala Lys Gly Ile Ile Asn Gln Thr Asn Asn Pro Thr Met Asp Thr 290
295 300 Ser Ala Ile Thr Gln Ala
Thr Thr Gln Val Asn Asn Ala Lys Asn Gly305 310
315 320 Leu Asn Gly Ala Glu Asn Leu Arg Asn Ala Gln
Asn Thr Ala Lys Gln 325 330
335 Asn Leu Asn Thr Leu Ser His Leu Thr Asn Asn Gln Lys Ser Ala Ile
340 345 350 Ser Ser Gln
Ile Asp Arg Ala Gly His Val Ser Glu Val Thr Ala Ala 355
360 365 Lys Asn Ala Ala Thr Glu Leu Asn
Ala Gln Met Gly Asn Leu Glu Gln 370 375
380 Ala Ile His Asp Gln Asn Thr Val Lys Gln Gly Val Asn
Phe Thr Asp385 390 395
400 Ala Asp Lys Ala Lys Arg Asp Ala Tyr Thr Asn Ala Val Ser Arg Ala
405 410 415 Glu Thr Ile Leu
Asn Lys Thr Gln Gly Ala Asn Thr Ser Lys Gln Asp 420
425 430 Val Glu Ala Ala Ile Gln Asn Val Thr
Ser Ala Lys Asn Ala Leu Asn 435 440
445 Gly Asp Gln Asn Val Thr Asn Ala Lys Asn Ala Ala Lys Asn
Ala Leu 450 455 460
Asn Asn Leu Thr Ser Ile Asn Asn Ala Gln Lys Arg Asp Leu Thr Thr465
470 475 480 Lys Ile Asp Gln Ala
Thr Thr Val Ala Gly Val Glu Ala Val Ser Asn 485
490 495 Thr Gly Thr Gln Leu Asn Thr Ala Met Ala
Asn Leu Gln Asn Gly Ile 500 505
510 Asn Asp Lys Ala Asn Thr Leu Ala Ser Glu Asn Tyr His Asp Ala
Asp 515 520 525 Ser
Asp Lys Lys Thr Ala Tyr Thr Gln Ala Val Thr Asn Ala Glu Asn 530
535 540 Ile Leu Asn Lys Asn Ser
Gly Ser Asn Leu Asp Lys Ala Ala Val Glu545 550
555 560 Asn Ala Leu Ser Gln Val Thr Asn Ala Lys Gly
Ala Leu Asn Gly Asn 565 570
575 His Asn Leu Glu Gln Ala Lys Ser Asn Ala Asn Thr Thr Ile Asn Gly
580 585 590 Leu Gln His
Leu Thr Thr Ala Gln Lys Asp Lys Leu Lys Gln Gln Val 595
600 605 Gln Gln Ala Gln Asn Val Ala Gly
Val Asp Thr Val Lys Ser Ser Ala 610 615
620 Asn Thr Leu Asn Gly Ala Met Gly Thr Leu Arg Asn Ser
Ile Gln Asp625 630 635
640 Asn Thr Ala Thr Lys Asn Gly Gln Asn Tyr Leu Asp Ala Thr Glu Arg
645 650 655 Asn Lys Thr Asn
Tyr Asn Asn Ala Val Asp Ser Ala Asn Gly Val Ile 660
665 670 Asn Ala Thr Ser Asn Pro Asn Met Asp
Ala Asn Ala Ile Asn Gln Ile 675 680
685 Ala Thr Gln Val Thr Ser Thr Lys Asn Ala Leu Asp Gly Thr
His Asn 690 695 700
Leu Thr Gln Ala Lys Gln Thr Ala Thr Asn Ala Ile Asp Gly Ala Thr705
710 715 720 Asn Leu Asn Lys Ala
Gln Lys Asp Ala Leu Lys Ala Gln Val Thr Ser 725
730 735 Ala Gln Arg Val Ala Asn Val Thr Ser Ile
Gln Gln Thr Ala Asn Glu 740 745
750 Leu Asn Thr Ala Met Gly Gln Leu Gln His Gly Ile Asp Asp Glu
Asn 755 760 765 Ala
Thr Lys Gln Thr Gln Lys Tyr Arg Asp Ala Glu Gln Ser Lys Lys 770
775 780 Thr Ala Tyr Asp Gln Ala
Val Ala Ala Ala Lys Ala Ile Leu Asn Lys785 790
795 800 Gln Thr Gly Ser Asn Ser Asp Lys Ala Ala Val
Asp Arg Ala Leu Gln 805 810
815 Gln Val Thr Ser Thr Lys Asp Ala Leu Asn Gly Asp Ala Lys Leu Ala
820 825 830 Glu Ala Lys
Ala Ala Ala Arg Gln Asn Leu Gly Thr Leu Asn His Ile 835
840 845 Thr Asn Ala Gln Arg Thr Ala Leu
Glu Gly Gln Ile Asn Gln Ala Thr 850 855
860 Thr Val Asp Gly Val Asn Thr Val Lys Thr Asn Ala Asn
Thr Leu Asp865 870 875
880 Gly Ala Met Asn Ser Leu Gln Gly Ala Ile Asn Asp Lys Asp Ala Thr
885 890 895 Leu Arg Asn Gln
Asn Tyr Leu Asp Ala Asp Glu Ser Lys Arg Asn Ala 900
905 910 Tyr Thr Gln Ala Val Thr Ala Ala Glu
Gly Ile Leu Asn Lys Gln Thr 915 920
925 Gly Gly Asn Thr Ser Lys Ala Asp Val Asp Asn Ala Leu Asn
Ala Val 930 935 940
Thr Arg Ala Lys Ala Ala Leu Asn Gly Ala Glu Asn Leu Arg Asn Ala945
950 955 960 Lys Thr Ser Ala Thr
Asn Thr Ile Asn Gly Leu Pro Asn Leu Thr Gln 965
970 975 Leu Gln Lys Asp Asn Leu Lys His Gln Val
Glu Gln Ala Gln Asn Val 980 985
990 Val Gly Val Asn Gly Val Lys Asp Lys Gly Asn Thr Leu Asn Thr
Ala 995 1000 1005 Met
Gly Ala Leu Arg Thr Ser Ile Gln Asn Asp Asn Thr Thr Lys Thr 1010
1015 1020 Ser Gln Asn Tyr Leu Asp
Ala Ser Asp Ser Asn Lys Asn Asn Tyr Asn1025 1030
1035 1040Thr Ala Val Asn Asn Ala Asn Gly Val Ile Asn
Ala Thr Asn Asn Pro 1045 1050
1055 Asn Met Asp Ala Asn Ala Ile Asn Asp Met Ala Asn Gln Val Asn Thr
1060 1065 1070 Thr Lys Ala
Ala Leu Asn Gly Ala Gln Asn Leu Ala Gln Ala Lys Thr 1075
1080 1085 Asn Ala Thr Asn Thr Ile Asn Asn
Ala Gln Asp Leu Asn Gln Lys Gln 1090 1095
1100 Lys Asp Ala Leu Lys Thr Gln Val Asn Asn Ala Gln Arg
Val Ser Asp1105 1110 1115
1120Ala Asn Asn Val Gln His Thr Ala Thr Glu Leu Asn Gly Ala Met Thr
1125 1130 1135 Ala Leu Lys Ala
Ala Ile Ala Asp Lys Glu Arg Thr Lys Ala Ser Gly 1140
1145 1150 Asn Tyr Val Asn Ala Asp Gln Glu Lys
Arg Gln Ala Tyr Asp Ser Lys 1155 1160
1165 Val Thr Asn Ala Glu Asn Ile Ile Asn Gly Thr Pro Asn Ala
Thr Leu 1170 1175 1180
Thr Val Asn Asp Val Asn Ser Ala Ala Ser Gln Val Asn Ala Ala Lys1185
1190 1195 1200Thr Ala Leu Asn Gly
Asp Asn Asn Leu Arg Val Ala Lys Glu His Ala 1205
1210 1215 Asn Asn Thr Ile Asp Gly Leu Ala Gln Leu
Asn Asn Val Gln Lys Ala 1220 1225
1230 Lys Leu Lys Glu Gln Val Gln Ser Ala Thr Thr Leu Asp Gly Val
Gln 1235 1240 1245 Thr
Val Lys Asn Ser Ser Gln Thr Leu Asn Thr Ala Met Lys Gly Leu 1250
1255 1260 Arg Asp Ser Ile Ala Asn
Glu Ala Thr Ile Lys Ala Gly Gln Asn Tyr1265 1270
1275 1280Thr Asp Ala Ser Pro Asn Asn Arg Asn Glu Tyr
Asp Ser Ala Val Thr 1285 1290
1295 Ala Ala Lys Ala Ile Ile Asn Gln Thr Ser Asn Pro Thr Met Glu Pro
1300 1305 1310 Asn Thr Ile
Thr Gln Ala Thr Ser Gln Val Thr Thr Lys Glu His Ala 1315
1320 1325 Leu Asn Gly Ala Gln Asn Leu Ala
Gln Ala Lys Thr Thr Ala Lys Asn 1330 1335
1340 Asn Leu Asn Asn Leu Thr Ser Ile Asn Asn Ala Gln Lys
Asp Ala Leu1345 1350 1355
1360Thr Arg Asn Ile Asp Gly Ala Thr Thr Val Ala Gly Val Asn Gln Glu
1365 1370 1375 Thr Ala Lys Ala
Thr Glu Leu Asn Asn Ala Met His Ser Leu Gln Asn 1380
1385 1390 Gly Ile Asn Asp Glu Thr Gln Thr Lys
Gln Thr Gln Lys Tyr Leu Asp 1395 1400
1405 Ala Glu Pro Ser Lys Lys Ser Ala Tyr Asp Gln Ala Val Asn
Ala Ala 1410 1415 1420
Lys Ala Ile Leu Thr Lys Ala Ser Gly Gln Asn Val Asp Lys Ala Ala1425
1430 1435 1440Val Glu Gln Ala Leu
Gln Asn Val Asn Ser Thr Lys Thr Ala Leu Asn 1445
1450 1455 Gly Asp Ala Lys Leu Asn Glu Ala Lys Ala
Ala Ala Lys Gln Thr Leu 1460 1465
1470 Gly Thr Leu Thr His Ile Asn Asn Ala Gln Arg Asn Ala Leu Asp
Asn 1475 1480 1485 Glu
Ile Thr Gln Ala Thr Asn Val Glu Gly Val Asn Thr Val Lys Ala 1490
1495 1500 Lys Ala Gln Gln Leu Asp
Gly Ala Met Gly Gln Leu Glu Thr Ser Ile1505 1510
1515 1520Arg Asp Lys Asp Thr Thr Leu Gln Ser Gln Asn
Tyr Gln Asp Ala Asp 1525 1530
1535 Asp Ala Lys Arg Thr Ala Tyr Ser Gln Ala Val Asn Ala Ala Ala Thr
1540 1545 1550 Ile Leu Asn
Lys Thr Ala Gly Gly Asn Thr Pro Lys Ala Asp Val Glu 1555
1560 1565 Arg Ala Met Gln Ala Val Thr Gln
Ala Asn Thr Ala Leu Asn Gly Ile 1570 1575
1580 Gln Asn Leu Glu Arg Ala Lys Gln Ala Ala Asn Thr Ala
Ile Thr Asn1585 1590 1595
1600Ala Ser Asp Leu Asn Thr Lys Gln Lys Glu Ala Leu Lys Ala Gln Val
1605 1610 1615 Thr Ser Ala Gly
Arg Val Ser Ala Ala Asn Gly Val Glu His Thr Ala 1620
1625 1630 Thr Glu Leu Asn Thr Ala Met Thr Ala
Leu Lys Arg Ala Ile Ala Asp 1635 1640
1645 Lys Ala Asp Thr Lys Ala Ser Gly Asn Tyr Val Asn Ala Asp
Ala Asn 1650 1655 1660
Lys Arg Gln Ala Tyr Asp Glu Lys Val Thr Ala Ala Glu His Ile Val1665
1670 1675 1680Ser Gly Thr Pro Thr
Pro Thr Leu Thr Pro Ser Asp Val Thr Asn Ala 1685
1690 1695 Ala Thr Gln Val Thr Asn Ala Lys Thr Gln
Leu Asn Gly Asn His Asn 1700 1705
1710 Leu Glu Val Ala Lys Gln Asn Ala Asn Thr Ala Ile Asp Gly Leu
Thr 1715 1720 1725 Ser
Leu Asn Gly Pro Gln Lys Ala Lys Leu Lys Glu Gln Val Gly Gln 1730
1735 1740 Ala Thr Thr Leu Pro Asn
Val Gln Thr Val Arg Asp Asn Ala Gln Thr1745 1750
1755 1760Leu Asn Thr Ala Met Lys Gly Leu Arg Asp Ser
Ile Ala Asn Glu Ala 1765 1770
1775 Thr Ile Lys Ala Gly Gln Asn Tyr Thr Asp Ala Ser Gln Asn Lys Gln
1780 1785 1790 Asn Asp Tyr
Asn Asn Ala Val Thr Ala Ala Lys Ala Ile Ile Gly Gln 1795
1800 1805 Thr Thr Ser Pro Ser Met Ile Ala
Gln Glu Ile Asn Gln Ala Lys Asp 1810 1815
1820 Gln Val Thr Ala Lys Gln Gln Ala Leu Asn Gly Gln Glu
Asn Leu Arg1825 1830 1835
1840Thr Ala Gln Thr Asn Ala Lys Gln His Leu Asn Gly Leu Ser Asp Leu
1845 1850 1855 Thr Asn Ala Gln
Lys Asp Ala Ala Lys Arg Gln Ile Glu Gly Ala Thr 1860
1865 1870 His Val Asn Glu Val Thr Gln Ala Gln
Asn Asn Ala Asp Ala Leu Asn 1875 1880
1885 Thr Ala Met Thr Asn Leu Lys Asn Gly Ile Gln Asp Gln Asn
Thr Ile 1890 1895 1900
Lys Gln Gly Val Asn Phe Thr Asp Ala Asp Glu Ala Lys Arg Asn Ala1905
1910 1915 1920Tyr Thr Asn Ala Val
Thr Gln Ala Glu Gln Ile Leu Asn Lys Ala Gln 1925
1930 1935 Gly Pro Asn Thr Ala Lys Asp Gly Val Glu
Thr Ala Leu Gln Asn Val 1940 1945
1950 Gln Arg Ala Lys Asn Glu Leu Asn Gly Asn Gln Asn Val Ala Asn
Ala 1955 1960 1965 Lys
Thr Thr Ala Lys Asn Ala Leu Asn Asn Leu Thr Ser Ile Asn Asn 1970
1975 1980 Ala Gln Lys Ala Ala Leu
Lys Ser Gln Ile Glu Gly Ala Thr Thr Val1985 1990
1995 2000Ala Gly Val Asn Gln Val Ser Thr Met Ala Ser
Glu Leu Asn Thr Ala 2005 2010
2015 Met Ser Asn Leu Gln Arg Gly Ile Asn Asp Glu Ala Ala Thr Lys Ala
2020 2025 2030 Ala Gln Lys
Tyr Thr Glu Ala Asp Arg Asp Lys Gln Thr Ala Tyr Asn 2035
2040 2045 Asp Ala Val Thr Ala Ala Lys Thr
Leu Leu Asp Lys Thr Ala Gly Ser 2050 2055
2060 Asn Asp Asn Lys Val Ala Val Glu Gln Ala Leu Gln Arg
Val Asn Thr2065 2070 2075
2080Ala Lys Thr Ala Leu Asn Gly Asp Ala Arg Leu Asn Glu Ala Lys Asn
2085 2090 2095 Thr Ala Lys Gln
Gln Leu Ala Thr Met Ser His Leu Thr Asn Ala Gln 2100
2105 2110 Lys Ala Asn Leu Thr Glu Gln Ile Glu
Arg Gly Thr Thr Val Ala Gly 2115 2120
2125 Val Gln Gly Ile Gln Ala Asn Ala Gly Thr Leu Asn Gln Ala
Met Asn 2130 2135 2140
Gln Leu Arg Gln Ser Ile Ala Ser Lys Asp Ala Thr Lys Ser Ser Glu2145
2150 2155 2160Asp Tyr Gln Asp Ala
Asn Ala Asp Leu Gln Asn Ala Tyr Asn Asp Ala 2165
2170 2175 Val Thr Asn Ala Glu Gly Ile Ile Ser Ala
Thr Asn Asn Pro Glu Met 2180 2185
2190 Asn Pro Asp Thr Ile Asn Gln Lys Ala Ser Gln Val Asn Ser Ala
Lys 2195 2200 2205 Ser
Ala Leu Asn Gly Asp Glu Lys Leu Ala Ala Val Lys Gln Thr Ala 2210
2215 2220 Lys Ser Asp Ile Gly Arg
Leu Thr Asp Leu Asn Asn Ala Gln Arg Thr2225 2230
2235 2240Ala Ala Asn Ala Glu Val Asp Gln Ala Pro Asn
Leu Ala Ala Val Thr 2245 2250
2255 Ala Ala Lys Asn Lys Ala Thr Ser Leu Asn Thr Ala Met Gly Asn Leu
2260 2265 2270 Lys His Ala
Leu Ala Glu Lys Asp Asn Thr Lys Arg Ser Val Asn Tyr 2275
2280 2285 Thr Asp Ala Asp Gln Pro Lys Gln
Gln Ala Tyr Asp Thr Ala Val Thr 2290 2295
2300 Gln Ala Glu Ala Ile Thr Asn Ala Asn Gly Ser Asn Ala
Asn Glu Thr2305 2310 2315
2320Gln Val Gln Ala Ala Leu Asn Gln Leu Asn Gln Ala Lys Asn Asp Leu
2325 2330 2335 Asn Gly Asp Asn
Lys Val Ala Gln Ala Lys Glu Thr Ala Lys Arg Ala 2340
2345 2350 Leu Ala Ser Tyr Ser Asn Leu Asn Asn
Ala Gln Ser Thr Ala Ala Thr 2355 2360
2365 Ser Gln Ile Asp Asn Ala Thr Thr Val Ala Asp Val Thr Ala
Ala Gln 2370 2375 2380
Asn Thr Ala Asn Glu Leu Asn Thr Ala Met Gly Gln Leu Gln Asn Gly2385
2390 2395 2400Ile Asn Asp Gln Asn
Thr Val Lys Gln Gln Val Asn Phe Thr Asp Ala 2405
2410 2415 Asp Gln Gly Lys Lys Asp Ala Tyr Thr Asn
Ala Val Thr Asn Ala Gln 2420 2425
2430 Gly Ile Leu Asp Lys Ala Asn Gly Gln Asn Met Thr Lys Ala Gln
Val 2435 2440 2445 Glu
Ala Ala Leu Asn Gln Val Thr Thr Ala Lys Asn Ala Leu Asn Gly 2450
2455 2460 Asp Ala Asn Val Arg Gln
Ala Lys Ser Asp Ala Lys Ala Asn Leu Gly2465 2470
2475 2480Thr Leu Thr His Leu Asn Asn Ala Gln Lys Gln
Asp Leu Thr Ser Gln 2485 2490
2495 Ile Glu Gly Ala Thr Thr Val Asn Gly Val Asn Ser Val Lys Thr Lys
2500 2505 2510 Ala Gln Asp
Leu Asp Gly Ala Met Gln Arg Leu Glu Ser Ala Ile Ala 2515
2520 2525 Asn Lys Asp Gln Thr Lys Ala Ser
Glu Asn Tyr Ile Asp Ala Asp Pro 2530 2535
2540 Thr Lys Lys Thr Ala Phe Asp Asn Ala Ile Thr Gln Ala
Glu Ser Tyr2545 2550 2555
2560Leu Asn Lys Asp His Gly Thr Asn Lys Asp Lys Gln Ala Val Glu Gln
2565 2570 2575 Ala Ile Gln Ser
Val Thr Ser Thr Glu Asn Ala Leu Asn Gly Asp Ala 2580
2585 2590 Asn Leu Gln Cys Ala Lys Thr Glu Ala
Thr Gln Ala Ile Asp Asn Leu 2595 2600
2605 Thr Gln Leu Asn Thr Pro Gln Lys Thr Ala Leu Lys Gln Gln
Val Asn 2610 2615 2620
Ala Ala Gln Arg Val Ser Gly Val Thr Asp Leu Lys Asn Ser Ala Thr2625
2630 2635 2640Ser Leu Asn Asn Ala
Met Asp Gln Leu Lys Gln Ala Ile Gly Asp His 2645
2650 2655 Asp Thr Ile Val Ala Gly Gly Asn Tyr Thr
Asn Ala Ser Pro Asp Lys 2660 2665
2670 Gln Gly Ala Tyr Thr Asp Ala Tyr Asn Ala Ala Lys Asn Ile Val
Asn 2675 2680 2685 Gly
Ser Pro Asn Val Ile Thr Asn Ala Ala Asp Val Thr Ala Ala Thr 2690
2695 2700 Gln Arg Val Asn Asn Ala
Glu Thr Ser Leu Asn Gly Asp Thr Asn Leu2705 2710
2715 2720Ala Thr Ala Lys Gln Gln Ala Lys Asp Ala Leu
Arg Gln Met Thr His 2725 2730
2735 Leu Ser Asp Ala Gln Lys Gln Ser Ile Thr Gly Gln Ile Asp Ser Ala
2740 2745 2750 Thr Gln Val
Thr Gly Val Gln Ser Val Lys Asp Asn Ala Thr Asn Leu 2755
2760 2765 Asp Asn Ala Met Asn Gln Leu Arg
Asn Ser Ile Ala Asn Lys Asp Glu 2770 2775
2780 Val Lys Ala Ser Gln Pro Tyr Val Asp Ala Asp Thr Asp
Lys Gln Asn2785 2790 2795
2800Ala Tyr Asn Thr Ala Val Thr Ser Ala Glu Asn Ile Ile Asn Ala Thr
2805 2810 2815 Ser Gln Pro Thr
Leu Asp Pro Ser Ala Val Thr Gln Ala Ala Asn Gln 2820
2825 2830 Val Asn Thr Asn Lys Thr Ala Leu Asn
Gly Ala Gln Asn Leu Ala Asn 2835 2840
2845 Lys Lys Gln Glu Thr Thr Ala Asn Ile Asn Arg Leu Ser His
Leu Asn 2850 2855 2860
Asn Ala Gln Lys Gln Asp Leu Asn Thr Gln Val Thr Asn Ala Pro Asn2865
2870 2875 2880Ile Ser Thr Val Asn
Gln Val Lys Thr Lys Ala Glu Gln Leu Asp Gln 2885
2890 2895 Ala Met Glu Arg Leu Ile Asn Gly Ile Gln
Asp Lys Asp Gln Val Lys 2900 2905
2910 Gln Ser Val Asn Phe Thr Asp Ala Asp Pro Glu Lys Gln Thr Ala
Tyr 2915 2920 2925 Asn
Asn Ala Val Thr Ala Ala Glu Asn Ile Ile Asn Gln Ala Asn Gly 2930
2935 2940 Thr Asn Ala Asn Gln Ser
Gln Val Glu Ala Ala Leu Ser Thr Val Thr2945 2950
2955 2960Thr Thr Lys Gln Ala Leu Asn Gly Asp Arg Lys
Val Thr Asp Ala Lys 2965 2970
2975 Asn Asn Ala Asn Gln Thr Leu Ser Thr Leu Asp Asn Leu Asn Asn Ala
2980 2985 2990 Gln Lys Gly
Ala Val Thr Gly Asn Ile Asn Gln Ala His Thr Val Ala 2995
3000 3005 Glu Val Thr Gln Ala Ile Gln Thr
Ala Gln Glu Leu Asn Thr Ala Met 3010 3015
3020 Gly Asn Leu Lys Asn Ser Leu Asn Asp Lys Asp Thr Thr
Leu Gly Ser3025 3030 3035
3040Gln Asn Phe Ala Asp Ala Asp Pro Glu Lys Lys Asn Ala Tyr Asn Glu
3045 3050 3055 Ala Val Arg Asn
Ala Glu Asn Ile Leu Asn Lys Ser Thr Gly Thr Asn 3060
3065 3070 Val Pro Lys Asp Gln Val Glu Ala Ala
Met Asn Gln Val Asn Thr Thr 3075 3080
3085 Lys Ala Ala Leu Asn Gly Thr Gln Asn Leu Glu Lys Ala Lys
Gln His 3090 3095 3100
Ala Asn Thr Ala Ile Asp Gly Leu Ser His Leu Thr Asn Ala Gln Lys3105
3110 3115 3120Glu Ala Leu Lys Gln
Leu Val Gln Gln Ser Thr Thr Val Ala Glu Ala 3125
3130 3135 Gln Gly Asn Glu Gln Lys Ala Asn Asn Val
Asp Ala Ala Met Asp Lys 3140 3145
3150 Leu Arg Gln Ser Ile Ala Asp Asn Ala Thr Thr Lys Gln Asn Gln
Asn 3155 3160 3165 Tyr
Thr Asp Ala Ser Pro Asn Lys Lys Asp Ala Tyr Asn Asn Ala Val 3170
3175 3180 Thr Thr Ala Gln Gly Ile
Ile Asp Gln Thr Thr Asn Pro Ser Leu Asp3185 3190
3195 3200Pro Thr Val Ile Asn Gln Ala Ala Gly Gln Val
Ser Thr Ser Lys Asn 3205 3210
3215 Ala Leu Asn Gly Asn Glu Asn Leu Glu Ala Ala Lys Gln Gln Ala Thr
3220 3225 3230 Gln Ser Leu
Gly Ser Leu Asp Asn Leu Asn Asn Ala Gln Lys Gln Ala 3235
3240 3245 Val Thr Asn Gln Ile Asn Gly Ala
His Thr Val Asp Glu Ala Asn Gln 3250 3255
3260 Ile Lys Gln Asn Ala Gln Asn Leu Asn Thr Ala Met Gly
Asn Leu Lys3265 3270 3275
3280Gln Ala Ile Ala Asp Lys Asp Ala Thr Lys Ala Thr Val Asn Phe Thr
3285 3290 3295 Asp Ala Asp Gln
Ala Lys Gln Gln Ala Tyr Asn Thr Ala Val Thr Asn 3300
3305 3310 Ala Glu Asn Ile Ile Ser Lys Ala Asn
Gly Gly Asn Ala Thr Gln Thr 3315 3320
3325 Glu Val Glu Gln Ala Ile Gln Gln Val Asn Ala Ala Lys Gln
Ala Leu 3330 3335 3340
Asn Gly Asn Ala Asn Val Gln His Ala Lys Asp Glu Ala Thr Ala Leu3345
3350 3355 3360Ile Asn Asn Ser Asn
Asp Leu Asn Gln Ala Gln Lys Asp Ala Leu Lys 3365
3370 3375 Gln Gln Val Gln Asn Ala Thr Thr Val Ala
Gly Val Asn Asn Val Lys 3380 3385
3390 Gln Thr Ala Gln Glu Leu Asn Asn Ala Met Thr Gln Leu Lys Gln
Gly 3395 3400 3405 Ile
Ala Asp Lys Glu Gln Thr Lys Ala Asp Gly Asn Phe Val Asn Ala 3410
3415 3420 Asp Ser Asp Lys Gln Asn
Ala Tyr Asn Gln Ala Val Ala Lys Ala Glu3425 3430
3435 3440Ala Leu Ile Ser Gly Thr Pro Asp Val Val Val
Thr Pro Ser Glu Ile 3445 3450
3455 Thr Ala Ala Leu Asn Lys Val Thr Gln Ala Lys Asn Asp Leu Asn Gly
3460 3465 3470 Asn Thr Asn
Leu Ala Thr Ala Lys Gln Asn Val Gln His Ala Ile Asp 3475
3480 3485 Gln Leu Pro Asn Leu Asn Gln Ala
Gln Arg Asp Glu Tyr Ser Lys Gln 3490 3495
3500 Ile Thr Gln Ala Thr Leu Val Pro Asn Val Asn Ala Ile
Gln Gln Ala3505 3510 3515
3520Ala Thr Thr Leu Asn Asp Ala Met Thr Gln Leu Lys Gln Gly Ile Ala
3525 3530 3535 Asn Lys Ala Gln
Ile Lys Gly Ser Glu Asn Tyr His Asp Ala Asp Thr 3540
3545 3550 Asp Lys Gln Thr Ala Tyr Asp Asn Ala
Val Thr Lys Ala Glu Glu Leu 3555 3560
3565 Leu Lys Gln Thr Thr Asn Pro Thr Met Asp Pro Asn Thr Ile
Gln Gln 3570 3575 3580
Ala Leu Thr Lys Val Asn Asp Thr Asn Gln Ala Leu Asn Gly Asn Gln3585
3590 3595 3600Lys Leu Ala Asp Ala
Lys Gln Asp Ala Lys Thr Thr Leu Gly Thr Leu 3605
3610 3615 Asp His Leu Asn Asp Ala Gln Lys Gln Ala
Leu Thr Thr Gln Val Glu 3620 3625
3630 Gln Ala Pro Asp Ile Ala Thr Val Asn Asn Val Lys Gln Asn Ala
Gln 3635 3640 3645 Asn
Leu Asn Asn Ala Met Thr Asn Leu Asn Asn Ala Leu Gln Asp Lys 3650
3655 3660 Thr Glu Thr Leu Asn Ser
Ile Asn Phe Thr Asp Ala Asp Gln Ala Lys3665 3670
3675 3680Lys Asp Asp Tyr Thr Asn Ala Val Ser His Ala
Glu Gly Ile Leu Ser 3685 3690
3695 Lys Ala Asn Gly Ser Asn Ala Ser Gln Thr Glu Val Glu Gln Ala Met
3700 3705 3710 Gln Arg Val
Asn Glu Ala Lys Gln Ala Leu Asn Gly Asn Asp Asn Val 3715
3720 3725 Gln Arg Ala Lys Asp Ala Ala Lys
Gln Val Ile Thr Asn Ala Asn Asp 3730 3735
3740 Leu Asn Gln Ala Gln Lys Asp Ala Leu Lys Gln Gln Val
Asp Ala Ala3745 3750 3755
3760Gln Thr Val Ala Asn Val Asn Thr Ile Lys Gln Thr Ala Gln Asp Leu
3765 3770 3775 Asn Gln Ala Met
Thr Gln Leu Lys Gln Gly Ile Ala Asp Lys Asp Gln 3780
3785 3790 Thr Lys Ala Asn Gly Asn Phe Val Asn
Ala Asp Thr Asp Lys Gln Asn 3795 3800
3805 Ala Tyr Asn Asn Ala Val Ala His Ala Glu Gln Ile Ile Ser
Gly Thr 3810 3815 3820
Pro Asn Ala Asn Val Asp Pro Gln Gln Val Ala Gln Ala Leu Gln Gln3825
3830 3835 3840Val Asn Gln Ala Lys
Gly Asp Leu Asn Gly Asn His Asn Leu Gln Val 3845
3850 3855 Ala Lys Asp Asn Ala Asn Thr Ala Ile Asp
Gln Leu Pro Asn Leu Asn 3860 3865
3870 Gln Pro Gln Lys Thr Ala Leu Lys Asp Gln Val Ser His Ala Glu
Leu 3875 3880 3885 Val
Thr Gly Val Asn Ala Ile Lys Gln Asn Ala Asp Ala Leu Asn Asn 3890
3895 3900 Ala Met Gly Thr Leu Lys
Gln Gln Ile Gln Ala Asn Ser Gln Val Pro3905 3910
3915 3920Gln Ser Val Asp Phe Thr Gln Ala Asp Gln Asp
Lys Gln Gln Ala Tyr 3925 3930
3935 Asn Asn Ala Ala Asn Gln Ala Gln Gln Ile Ala Asn Gly Thr Pro Thr
3940 3945 3950 Pro Val Leu
Ala Pro Asp Thr Val Thr Lys Ala Val Thr Thr Met Asn 3955
3960 3965 Gln Ala Lys Asp Ala Leu Asn Gly
Asp Glu Lys Leu Ala Gln Ala Lys 3970 3975
3980 Gln Asp Ala Leu Ala Asn Leu Asp Thr Leu Arg Asp Leu
Asn Gln Pro3985 3990 3995
4000Gln Arg Asp Ala Leu Arg Asn Gln Ile Asn Gln Ala Gln Ala Leu Ala
4005 4010 4015 Thr Val Glu Gln
Thr Lys Gln Asn Ala Gln Asn Val Asn Thr Ala Met 4020
4025 4030 Gly Asn Leu Lys Gln Gly Ile Ala Asn
Lys Asp Thr Val Lys Ala Ser 4035 4040
4045 Glu Asn Tyr His Asp Ala Asp Val Asp Lys Gln Thr Ala Tyr
Thr Asn 4050 4055 4060
Ala Val Ser Gln Ala Glu Gly Ile Ile Asn Gln Thr Thr Asn Pro Thr4065
4070 4075 4080Leu Asn Pro Asp Asp
Ile Thr Arg Ala Leu Thr Gln Val Thr Asp Ala 4085
4090 4095 Lys Asn Ser Leu Asn Gly Glu Ala Lys Leu
Ala Thr Glu Lys Gln Asn 4100 4105
4110 Ala Lys Asp Ala Val Ser Gly Met Thr His Leu Asn Asp Ala Gln
Lys 4115 4120 4125 Gln
Ala Leu Lys Gly Gln Ile Asp Gln Ser Pro Glu Ile Ala Thr Val 4130
4135 4140 Asn Gln Val Lys Gln Thr
Ala Thr Ser Leu Asp Gln Ala Met Asp Gln4145 4150
4155 4160Leu Ser Gln Ala Ile Asn Asp Lys Asp Gln Ile
Leu Ala Asp Gly Asn 4165 4170
4175 Tyr Leu Asn Ala Asp Pro Asp Lys Gln Asn Ala Tyr Lys Gln Ala Val
4180 4185 4190 Ala Lys Ala
Glu Ala Leu Leu Asn Lys Gln Ser Gly Thr Asn Glu Val 4195
4200 4205 Gln Ala Gln Val Glu Ser Ile Thr
Asn Glu Val Asn Ala Ala Lys Gln 4210 4215
4220 Ala Leu Asn Gly Asn Asp Asn Leu Ala Asn Ala Lys Gln
Gln Ala Lys4225 4230 4235
4240Gln Gln Leu Ala Asn Leu Thr His Leu Asn Asp Ala Gln Lys Gln Ser
4245 4250 4255 Phe Glu Ser Gln
Ile Thr Gln Ala Pro Leu Val Thr Asp Val Thr Thr 4260
4265 4270 Ile Asn Gln Lys Ala Gln Thr Leu Asp
His Ala Met Glu Leu Leu Arg 4275 4280
4285 Asn Ser Val Ala Asp Asn Gln Thr Thr Leu Ala Ser Glu Asp
Tyr His 4290 4295 4300
Asp Ala Thr Ala Gln Arg Gln Asn Asp Tyr Asn Lys Ala Val Thr Ala4305
4310 4315 4320Ala Asn Asn Ile Ile
Asn Gln Thr Thr Ser Pro Thr Met Asn Pro Asp 4325
4330 4335 Asp Val Asn Gly Ala Thr Thr Gln Val Asn
Asn Thr Lys Val Ala Leu 4340 4345
4350 Asp Gly Asp Glu Asn Leu Ala Ala Ala Lys Gln Gln Ala Asn Asn
Arg 4355 4360 4365 Leu
Asp Gln Leu Asp His Leu Asn Asn Ala Gln Lys Gln Gln Leu Gln 4370
4375 4380 Ser Gln Ile Thr Gln Ser
Ser Asp Ile Ala Ala Val Asn Gly His Lys4385 4390
4395 4400Gln Thr Ala Glu Ser Leu Asn Thr Ala Met Gly
Asn Leu Ile Asn Ala 4405 4410
4415 Ile Ala Asp His Gln Ala Val Glu Gln Arg Gly Asn Phe Ile Asn Ala
4420 4425 4430 Asp Thr Asp
Lys Gln Thr Ala Tyr Asn Thr Ala Val Asn Glu Ala Ala 4435
4440 4445 Ala Met Ile Asn Lys Gln Thr Gly
Gln Asn Ala Asn Gln Thr Glu Val 4450 4455
4460 Glu Gln Ala Ile Thr Lys Val Gln Thr Thr Leu Gln Ala
Leu Asn Gly4465 4470 4475
4480Asp His Asn Leu Gln Val Ala Lys Thr Asn Ala Thr Gln Ala Ile Asp
4485 4490 4495 Val Leu Thr Ser
Leu Asn Asp Pro Gln Lys Thr Ala Leu Lys Asp Gln 4500
4505 4510 Val Thr Ala Ala Thr Leu Val Thr Ala
Val His Gln Ile Glu Gln Asn 4515 4520
4525 Ala Asn Thr Leu Asn Gln Ala Met His Gly Leu Arg Gln Ser
Ile Gln 4530 4535 4540
Asp Asn Ala Ala Thr Lys Ala Asn Ser Lys Tyr Ile Asn Glu Asp Gln4545
4550 4555 4560Pro Glu Gln Gln Asn
Tyr Asp Gln Ala Val Gln Ala Ala Asn Asn Ile 4565
4570 4575 Ile Asn Glu Gln Thr Ala Thr Leu Asp Asn
Asn Ala Ile Asn Gln Val 4580 4585
4590 Ala Ala Thr Val Asn Thr Thr Lys Ala Ala Leu His Gly Asp Val
Lys 4595 4600 4605 Leu
Gln Asn Asp Lys Asp His Ala Lys Gln Thr Val Ser Gln Leu Ala 4610
4615 4620 His Leu Asn Asn Ala Gln
Lys His Met Glu Asp Thr Leu Ile Asp Ser4625 4630
4635 4640Glu Thr Thr Arg Thr Ala Val Lys Gln Asp Leu
Thr Glu Val Gln Ala 4645 4650
4655 Leu Asp Gln Leu Met Asp Ala Leu Gln Gln Ser Ile Ala Asp Lys Asp
4660 4665 4670 Ala Thr Arg
Ala Ser Ser Ala Tyr Val Asn Ala Glu Pro Asn Lys Lys 4675
4680 4685 Gln Ala Tyr Asp Glu Ala Val Gln
Asn Ala Glu Ser Ile Ile Ala Gly 4690 4695
4700 Leu Asn Asn Pro Thr Ile Asn Lys Gly Asn Val Ser Ser
Ala Thr Gln4705 4710 4715
4720Ala Val Ile Ser Ser Lys Asn Ala Leu Asp Gly Val Glu Arg Leu Ala
4725 4730 4735 Gln Asp Lys Gln
Thr Ala Gly Asn Ser Leu Asn His Leu Asp Gln Leu 4740
4745 4750 Thr Pro Ala Gln Gln Gln Ala Leu Glu
Asn Gln Ile Asn Asn Ala Thr 4755 4760
4765 Thr Cys Asp Lys Val Ala Glu Ile Ile Ala Gln Ala Gln Ala
Leu Asn 4770 4775 4780
Glu Ala Met Lys Ala Leu Lys Glu Ser Ile Lys Asp Gln Pro Gln Thr4785
4790 4795 4800Glu Ala Ser Ser Lys
Phe Ile Asn Glu Asp Gln Ala Gln Lys Asp Ala 4805
4810 4815 Tyr Thr Gln Ala Val Gln His Ala Lys Asp
Leu Ile Asn Lys Thr Thr 4820 4825
4830 Asp Pro Thr Leu Ala Lys Ser Ile Ile Asp Gln Ala Thr Gln Ala
Val 4835 4840 4845 Thr
Asp Ala Lys Asn Asn Leu His Gly Asp Gln Lys Leu Ala Gln Asp 4850
4855 4860 Lys Gln Arg Ala Thr Glu
Thr Leu Asn Asn Leu Ser Asn Leu Asn Thr4865 4870
4875 4880Pro Gln Arg Gln Ala Leu Glu Asn Gln Ile Asn
Asn Ala Ala Thr Arg 4885 4890
4895 Gly Glu Val Ala Gln Lys Leu Thr Glu Ala Gln Ala Leu Asn Gln Ala
4900 4905 4910 Met Glu Ala
Leu Arg Asn Ser Ile Gln Asp Gln Gln Gln Thr Glu Ser 4915
4920 4925 Gly Ser Lys Phe Ile Asn Glu Asp
Lys Pro Gln Lys Asp Ala Tyr Gln 4930 4935
4940 Ala Ala Val Gln Asn Ala Lys Asp Leu Ile Asn Gln Thr
Gly Asn Pro4945 4950 4955
4960Thr Leu Asp Lys Ala Gln Val Glu Gln Leu Thr His Ala Phe Lys Gln
4965 4970 4975 Ala Lys Asp Asn
Leu His Gly Asp Gln Lys Leu Ala Asp Asp Lys Gln 4980
4985 4990 His Ala Val Thr Asp Leu Asn Gln Leu
Asn Gly Leu Asn Asn Pro Gln 4995 5000
5005 Arg Gln Ala Leu Glu Ser Gln Ile Asn Asn Ala Ala Thr Arg
Gly Glu 5010 5015 5020
Val Ala Gln Lys Leu Ala Glu Ala Lys Ala Leu Asp Gln Ala Met Gln5025
5030 5035 5040Ala Leu Arg Asn Ser
Ile Gln Asp Gln Gln Gln Thr Glu Ala Gly Ser 5045
5050 5055 Lys Phe Ile Asn Glu Asp Lys Pro Gln Lys
Asp Ala Tyr Gln Ala Ala 5060 5065
5070 Val Gln Asn Ala Lys Asp Leu Ile Asn Gln Thr Gly Asn Pro Thr
Leu 5075 5080 5085 Asp
Lys Ser Gln Val Glu Gln Leu Thr Gln Ala Val Thr Thr Ala Lys 5090
5095 5100 Asp Asn Leu His Gly Asp
Gln Lys Leu Ala Arg Asp Gln Gln Gln Ala5105 5110
5115 5120Val Thr Thr Val Asn Ala Leu Pro Asn Leu Asn
His Ala Gln Gln Gln 5125 5130
5135 Thr Leu Thr Asp Ala Ile Asn Ala Ala Pro Thr Arg Thr Glu Val Ala
5140 5145 5150 Gln His Val
Gln Thr Ala Thr Glu Leu Asp His Ala Met Glu Thr Leu 5155
5160 5165 Lys Asn Lys Val Asp Gln Val Asn
Thr Asp Lys Ala Gln Pro Asn Tyr 5170 5175
5180 Thr Glu Ala Ser Thr Asp Lys Lys Glu Ala Val Asp Gln
Ala Leu Gln5185 5190 5195
5200Ala Ala Gln Ser Ile Thr Asp Pro Thr Asn Gly Ser Asn Ala Asn Lys
5205 5210 5215 Asp Ala Val Glu
Gln Ala Leu Thr Lys Leu Gln Glu Lys Val Asn Glu 5220
5225 5230 Leu Asn Gly Asn Glu Arg Val Ala Glu
Ala Lys Thr Gln Ala Lys Gln 5235 5240
5245 Thr Ile Asp Gln Leu Thr His Leu Asn Ala Asp Gln Ile Ala
Thr Ala 5250 5255 5260
Lys Gln Asn Ile Asp Gln Ala Thr Lys Leu Gln Pro Ile Ala Glu Leu5265
5270 5275 5280Val Asp Gln Ala Thr
Gln Leu Asn Gln Ser Met Asp Gln Leu Gln Gln 5285
5290 5295 Ala Val Asn Glu His Ala Asn Val Glu Gln
Thr Ile Asp Tyr Thr Gln 5300 5305
5310 Ala Asp Ser Asp Lys Gln Lys Ala Tyr Lys Gln Ala Ile Ala Asp
Ala 5315 5320 5325 Glu
Asn Val Leu Lys Gln Asn Ala Asn Lys Gln Gln Val Asp Gln Ala 5330
5335 5340 Leu Gln Asn Ile Leu Asn
Ala Lys Gln Ala Leu Asn Gly Asp Glu Arg5345 5350
5355 5360Val Ala Leu Ala Lys Thr Asn Gly Lys His Asp
Ile Asp Gln Leu Asn 5365 5370
5375 Ala Leu Asn Asn Ala Gln Gln Asp Gly Phe Lys Gly Arg Ile Asp Gln
5380 5385 5390 Ser Asn Asp
Leu Asn Gln Ile Gln Gln Ile Val Asp Glu Ala Lys Ala 5395
5400 5405 Leu Asn Arg Ala Met Asp Gln Leu
Ser Gln Glu Ile Thr Gly Asn Glu 5410 5415
5420 Gly Arg Thr Lys Gly Ser Thr Asn Tyr Val Asn Ala Asp
Thr Gln Val5425 5430 5435
5440Lys Gln Val Tyr Asp Glu Ala Val Asp Lys Ala Lys Gln Ala Leu Asp
5445 5450 5455 Lys Ser Ser Gly
Gln Asn Leu Thr Ala Glu Gln Val Ile Lys Leu Asn 5460
5465 5470 Asp Ala Val Thr Ala Ala Lys Lys Ala
Leu Asn Gly Glu Glu Arg Leu 5475 5480
5485 Asn Asn Arg Lys Ala Glu Ala Leu Gln Arg Leu Asp Gln Leu
Thr His 5490 5495 5500
Leu Asn Asn Ala Gln Arg Gln Leu Ala Ile Gln Gln Ile Asn Asn Ala5505
5510 5515 5520Glu Thr Leu Asn Lys
Ala Ser Arg Ala Ile Asn Arg Ala Thr Lys Leu 5525
5530 5535 Asp Asn Ala Met Gly Ala Val Gln Gln Tyr
Ile Asp Glu Gln His Leu 5540 5545
5550 Gly Val Ile Ser Ser Thr Asn Tyr Ile Asn Ala Asp Asp Asn Leu
Lys 5555 5560 5565 Ala
Asn Tyr Asp Asn Ala Ile Ala Asn Ala Ala His Glu Leu Asp Lys 5570
5575 5580 Val Gln Gly Asn Ala Ile
Ala Lys Ala Glu Ala Glu Gln Leu Lys Gln5585 5590
5595 5600Asn Ile Ile Asp Ala Gln Asn Ala Leu Asn Gly
Asp Gln Asn Leu Ala 5605 5610
5615 Asn Ala Lys Asp Lys Ala Asn Ala Phe Val Asn Ser Leu Asn Gly Leu
5620 5625 5630 Asn Gln Gln
Gln Gln Asp Leu Ala His Lys Ala Ile Asn Asn Ala Asp 5635
5640 5645 Thr Val Ser Asp Val Thr Asp Ile
Val Asn Asn Gln Ile Asp Leu Asn 5650 5655
5660 Asp Ala Met Glu Thr Leu Lys His Leu Val Asp Asn Glu
Ile Pro Asn5665 5670 5675
5680Ala Glu Gln Thr Val Asn Tyr Gln Asn Ala Asp Asp Asn Ala Lys Thr
5685 5690 5695 Asn Phe Asp Asp
Ala Lys Arg Leu Ala Asn Thr Leu Leu Asn Ser Asp 5700
5705 5710 Asn Thr Asn Val Asn Asp Ile Asn Gly
Ala Ile Gln Ala Val Asn Asp 5715 5720
5725 Ala Ile His Asn Leu Asn Gly Asp Gln Arg Leu Gln Asp Ala
Lys Asp 5730 5735 5740
Lys Ala Ile Gln Ser Ile Asn Gln Ala Leu Ala Asn Lys Leu Lys Glu5745
5750 5755 5760Ile Glu Ala Ser Asn
Ala Thr Asp Gln Asp Lys Leu Ile Ala Lys Asn 5765
5770 5775 Lys Ala Glu Glu Leu Ala Asn Ser Ile Ile
Asn Asn Ile Asn Lys Ala 5780 5785
5790 Thr Ser Asn Gln Ala Val Ser Gln Val Gln Thr Ala Gly Asn His
Ala 5795 5800 5805 Ile
Glu Gln Val His Ala Asn Glu Ile Pro Lys Ala Lys Ile Asp Ala 5810
5815 5820 Asn Lys Asp Val Asp Lys
Gln Val Gln Ala Leu Ile Asp Glu Ile Asp5825 5830
5835 5840Arg Asn Pro Asn Leu Thr Asp Lys Glu Lys Gln
Ala Leu Lys Asp Arg 5845 5850
5855 Ile Asn Gln Ile Leu Gln Gln Gly His Asn Asp Ile Asn Asn Ala Leu
5860 5865 5870 Thr Lys Glu
Glu Ile Glu Gln Ala Lys Ala Gln Leu Ala Gln Ala Leu 5875
5880 5885 Gln Asp Ile Lys Asp Leu Val Lys
Ala Lys Glu Asp Ala Lys Gln Asp 5890 5895
5900 Val Asp Lys Gln Val Gln Ala Leu Ile Asp Glu Ile Asp
Gln Asn Pro5905 5910 5915
5920Asn Leu Thr Asp Lys Glu Lys Gln Ala Leu Lys Asp Arg Ile Asn Gln
5925 5930 5935 Ile Leu Gln Gln
Gly His Asn Gly Ile Asn Asn Ala Met Thr Lys Glu 5940
5945 5950 Glu Ile Glu Gln Ala Lys Ala Gln Leu
Ala Gln Ala Leu Lys Glu Ile 5955 5960
5965 Lys Asp Leu Val Lys Ala Lys Glu Asn Ala Lys Gln Asp Val
Asp Lys 5970 5975 5980
Gln Val Gln Ala Leu Ile Asp Glu Ile Asp Gln Asn Pro Asn Leu Thr5985
5990 5995 6000Asp Lys Glu Lys Gln
Ala Leu Lys Asp Arg Ile Asn Gln Ile Leu Gln 6005
6010 6015 Gln Gly His Asn Asp Ile Asn Asn Ala Met
Thr Lys Glu Glu Ile Glu 6020 6025
6030 Gln Ala Lys Ala Gln Leu Ala Gln Ala Leu Gln Asp Ile Lys Asp
Leu 6035 6040 6045 Val
Lys Ala Lys Glu Asp Ala Lys Asn Ala Ile Lys Ala Leu Ala Asn 6050
6055 6060 Ala Lys Arg Asp Gln Ile
Asn Ser Asn Pro Asp Leu Thr Pro Glu Gln6065 6070
6075 6080Lys Ala Lys Ala Leu Lys Glu Ile Asp Glu Ala
Glu Lys Arg Ala Leu 6085 6090
6095 Gln Asn Val Glu Asn Ala Gln Thr Ile Asp Gln Leu Asn Arg Gly Leu
6100 6105 6110 Asn Leu Gly
Leu Asp Asp Ile Arg Asn Thr His Val Trp Glu Val Asp 6115
6120 6125 Glu Gln Pro Ala Val Asn Glu Ile
Phe Glu Ala Thr Pro Glu Gln Ile 6130 6135
6140 Leu Val Asn Gly Glu Leu Ile Val His Arg Asp Asp Ile
Ile Thr Glu6145 6150 6155
6160Gln Asp Ile Leu Ala His Ile Asn Leu Ile Asp Gln Leu Ser Ala Glu
6165 6170 6175 Val Ile Asp Thr
Pro Ser Thr Ala Thr Ile Ser Asp Ser Leu Thr Ala 6180
6185 6190 Lys Val Glu Val Thr Leu Leu Asp Gly
Ser Lys Val Ile Val Asn Val 6195 6200
6205 Pro Val Lys Val Val Glu Lys Glu Leu Ser Val Val Lys Gln
Gln Ala 6210 6215 6220
Ile Glu Ser Ile Glu Asn Ala Ala Gln Gln Lys Ile Asp Glu Ile Asn6225
6230 6235 6240Asn Ser Val Thr Leu
Thr Leu Glu Gln Lys Glu Ala Ala Ile Ala Glu 6245
6250 6255 Val Asn Lys Leu Lys Gln Gln Ala Ile Asp
His Val Asn Asn Ala Pro 6260 6265
6270 Asp Val His Ser Val Glu Glu Ile Gln Gln Gln Glu Gln Ala Tyr
Ile 6275 6280 6285 Glu
Gln Phe Asn Pro Glu Gln Phe Thr Ile Glu Gln Ala Lys Ser Asn 6290
6295 6300 Ala Ile Lys Ser Ile Glu
Asp Ala Ile Gln His Met Ile Asp Glu Ile6305 6310
6315 6320Lys Ala Arg Thr Asp Leu Thr Asp Lys Glu Lys
Gln Glu Ala Ile Ala 6325 6330
6335 Lys Leu Asn Gln Leu Lys Glu Gln Ala Ile Gln Ala Ile Gln Arg Ala
6340 6345 6350 Gln Ser Ile
Ser Glu Ile Thr Glu Gln Leu Glu Gln Phe Lys Ala Gln 6355
6360 6365 Met Lys Ala Ala Asn Pro Thr Ala
Lys Glu Leu Ala Lys Arg Lys Gln 6370 6375
6380 Glu Ala Ile Ser Arg Ile Lys Asp Phe Ser Asn Glu Lys
Ile Asn Ser6385 6390 6395
6400Ile Arg Asn Ser Glu Ile Gly Thr Ala Asp Glu Lys Gln Ala Ala Met
6405 6410 6415 Asn Gln Ile Asn
Glu Ile Val Leu Glu Thr Ile Arg Asp Ile Asn Asn 6420
6425 6430 Ala His Thr Leu Gln Gln Val Glu Ala
Ala Leu Asn Asn Gly Ile Ala 6435 6440
6445 Arg Ile Ser Ala Val Gln Ile Val Ile Ser Asp Arg Ala Lys
Gln Ser 6450 6455 6460
Ser Ser Thr Gly Asn Glu Ser Asn Ser His Leu Thr Ile Gly Tyr Gly6465
6470 6475 6480Thr Ala Asn His Pro
Phe Asn Ser Ser Thr Ile Gly His Lys Lys Lys 6485
6490 6495 Leu Asp Glu Asp Asp Asp Ile Asp Pro Leu
His Met Arg His Phe Ser 6500 6505
6510 Asn Asn Phe Gly Asn Val Ile Lys Asn Ala Ile Gly Val Val Gly
Ile 6515 6520 6525 Ser
Gly Leu Leu Ala Ser Phe Trp Phe Phe Ile Ala Lys Arg Arg Arg 6530
6535 6540 Lys Glu Asp Glu Glu Glu
Glu Leu Glu Ile Arg Asp Asn Asn Lys Asp6545 6550
6555 6560Ser Ile Lys Glu Thr Leu Asp Asp Thr Lys His
Leu Pro Leu Leu Phe 6565 6570
6575 Ala Lys Arg Arg Arg Lys Glu Asp Glu Glu Asp Val Thr Val Glu Glu
6580 6585 6590 Lys Asp Ser
Leu Asn Asn Gly Glu Ser Leu Asp Lys Val Lys His Thr 6595
6600 6605 Pro Phe Phe Leu Pro Lys Arg Arg
Arg Lys Glu Asp Glu Glu Asp Val 6610 6615
6620 Glu Val Thr Asn Glu Asn Thr Asp Glu Lys Val Leu Lys
Asp Asn Glu6625 6630 6635
6640His Ser Pro Leu Leu Phe Ala Lys Arg Arg Lys Asp Lys Glu Glu Asp
6645 6650 6655 Val Glu Thr Thr
Thr Ser Ile Glu Ser Lys Asp Glu Asp Val Pro Leu 6660
6665 6670 Leu Leu Ala Lys Lys Lys Asn Gln Lys
Asp Asn Gln Ser Lys Asp Lys 6675 6680
6685 Lys Ser Ala Ser Lys Asn Thr Ser Lys Lys Val Ala Ala Lys
Lys Lys 6690 6695 6700 Lys
Lys Lys Ser Lys Lys Asn Lys Lys6705 6710
14701PRTStaphylococcus sp. 14Met Asn Asn Arg Asp Lys Leu Gln Lys Phe Ser
Ile Arg Lys Tyr Ala1 5 10
15 Ile Gly Thr Phe Ser Thr Val Ile Ala Thr Leu Val Phe Met Gly Ile
20 25 30 Asn Thr Asn
His Ala Ser Ala Asp Glu Leu Asn Gln Asn Gln Lys Leu 35
40 45 Ile Lys Gln Leu Asn Gln Thr Asp
Asp Asp Asp Ser Asn Thr His Ser 50 55
60 Gln Glu Ile Glu Asn Asn Lys Gln Asn Ser Ser Gly Gln
Thr Glu Ser65 70 75 80
Leu Arg Ser Ser Thr Ser Gln Asn Gln Ala Asn Ala Arg Leu Ser Asp
85 90 95 Gln Phe Lys Asp Thr
Asn Glu Thr Ser Gln Gln Leu Pro Thr Asn Val 100
105 110 Ser Asp Asp Ser Ile Asn Gln Ser His Ser
Glu Ala Asn Met Asn Asn 115 120
125 Glu Pro Leu Lys Val Asp Asn Ser Thr Met Gln Ala His Ser
Lys Ile 130 135 140
Val Ser Asp Ser Asp Gly Asn Ala Ser Glu Asn Lys His His Lys Leu145
150 155 160 Thr Glu Asn Val Leu
Ala Glu Ser Arg Ala Ser Lys Asn Asp Lys Glu 165
170 175 Lys Glu Asn Leu Gln Glu Lys Asp Lys Ser
Gln Gln Val His Pro Pro 180 185
190 Leu Asp Lys Asn Ala Leu Gln Ala Phe Phe Asp Ala Ser Tyr His
Asn 195 200 205 Tyr
Arg Met Ile Asp Arg Asp Arg Ala Asp Ala Thr Glu Tyr Gln Lys 210
215 220 Val Lys Ser Thr Phe Asp
Tyr Val Asn Asp Leu Leu Gly Asn Asn Gln225 230
235 240 Asn Ile Pro Ser Glu Gln Leu Val Ser Ala Tyr
Gln Gln Leu Glu Lys 245 250
255 Ala Leu Glu Leu Ala Arg Thr Leu Pro Gln Gln Ser Thr Thr Glu Lys
260 265 270 Arg Gly Arg
Arg Ser Thr Arg Ser Val Val Glu Asn Arg Ser Ser Arg 275
280 285 Ser Asp Tyr Leu Asp Ala Arg Thr
Glu Tyr Tyr Val Ser Lys Asp Asp 290 295
300 Asp Asp Ser Gly Phe Pro Pro Gly Thr Phe Phe His Ala
Ser Asn Arg305 310 315
320 Arg Trp Pro Tyr Asn Leu Pro Arg Ser Arg Asn Ile Leu Arg Ala Ser
325 330 335 Asp Val Gln Gly
Asn Ala Tyr Ile Thr Thr Lys Arg Leu Lys Asp Gly 340
345 350 Tyr Gln Trp Asp Ile Leu Phe Asn Ser
Asn His Lys Gly His Glu Tyr 355 360
365 Met Tyr Tyr Trp Phe Gly Leu Pro Ser Asp Gln Thr Pro Thr
Gly Pro 370 375 380
Val Thr Phe Thr Ile Ile Asn Arg Asp Gly Ser Ser Thr Ser Thr Gly385
390 395 400 Gly Val Gly Phe Gly
Ser Gly Ala Pro Leu Pro Gln Phe Trp Arg Ser 405
410 415 Ala Gly Ala Ile Asn Ser Ser Val Ala Asn
Asp Phe Lys His Gly Ser 420 425
430 Ala Thr Asn Tyr Ala Phe Tyr Asp Gly Val Asn Asn Phe Ser Asp
Phe 435 440 445 Ala
Arg Gly Gly Glu Leu Tyr Phe Asp Arg Glu Gly Ala Thr Gln Thr 450
455 460 Asn Lys Tyr Tyr Gly Asp
Glu Asn Phe Ala Leu Leu Asn Ser Glu Lys465 470
475 480 Pro Asp Gln Ile Arg Gly Leu Asp Thr Ile Tyr
Ser Phe Lys Gly Ser 485 490
495 Gly Asp Val Ser Tyr Arg Ile Ser Phe Lys Thr Gln Gly Ala Pro Thr
500 505 510 Ala Arg Leu
Tyr Tyr Ala Ala Gly Ala Arg Ser Gly Glu Tyr Lys Gln 515
520 525 Ala Thr Asn Tyr Asn Gln Leu Tyr
Val Glu Pro Tyr Lys Asn Tyr Arg 530 535
540 Asn Arg Val Gln Ser Asn Val Gln Val Lys Asn Arg Thr
Leu His Leu545 550 555
560 Lys Arg Thr Ile Arg Gln Phe Asp Pro Thr Leu Gln Arg Thr Thr Asp
565 570 575 Val Pro Ile Leu
Asp Ser Asp Gly Ser Gly Ser Ile Asp Ser Val Tyr 580
585 590 Asp Pro Leu Ser Tyr Val Lys Asn Val
Thr Gly Thr Val Leu Gly Ile 595 600
605 Tyr Pro Ser Tyr Leu Pro Tyr Asn Gln Glu Arg Trp Gln Gly
Ala Asn 610 615 620
Ala Met Asn Ala Tyr Gln Ile Glu Glu Leu Phe Ser Gln Glu Asn Leu625
630 635 640 Gln Asn Ala Ala Arg
Ser Gly Arg Pro Ile Gln Phe Leu Val Gly Phe 645
650 655 Asp Val Glu Asp Ser His His Asn Pro Glu
Thr Leu Leu Pro Val Asn 660 665
670 Leu Tyr Val Lys Pro Glu Leu Lys His Thr Ile Glu Leu Tyr His
Asp 675 680 685 Asn
Glu Lys Gln Asp Arg Lys Glu Phe Ser Val Ser Lys 690
695 700 159439PRTStaphylococcus sp. 15Met Ser Gly Thr
Leu His Asn Thr Val Gly Ser Gly Ile Leu Pro Tyr1 5
10 15 Gln Gln Glu Ile Arg Ile Lys Leu Thr
Ser Asn Glu Pro Ile Lys Asp 20 25
30 Ser Glu Trp Ser Ile Thr Gly Tyr Pro Asn Thr Leu Thr Leu
Gln Asn 35 40 45
Ala Val Gly Arg Thr Asn Asn Ala Thr Glu Lys Asn Leu Ala Leu Val 50
55 60 Gly His Ile Asp Pro
Gly Asn Tyr Phe Ile Thr Val Lys Phe Gly Asp65 70
75 80 Lys Val Glu Gln Phe Glu Ile Arg Ser Lys
Pro Thr Pro Pro Arg Ile 85 90
95 Ile Thr Thr Ala Asn Glu Leu Arg Gly Asn Pro Asn His Lys Pro
Glu 100 105 110 Ile
Arg Val Thr Asp Ile Pro Asn Asp Thr Thr Ala Lys Ile Lys Leu 115
120 125 Val Met Gly Gly Thr Asp
Gly Asp His Asp Pro Glu Ile Asn Pro Tyr 130 135
140 Thr Val Pro Glu Asn Tyr Thr Val Val Ala Glu
Ala Tyr His Asp Asn145 150 155
160 Asp Pro Ser Lys Asn Gly Val Leu Thr Phe Arg Ser Ser Asp Tyr Leu
165 170 175 Lys Asp Leu
Pro Leu Ser Gly Glu Leu Lys Ala Ile Val Tyr Tyr Asn 180
185 190 Gln Tyr Val Gln Ser Asn Phe Ser
Lys Ser Val Pro Phe Ser Ser Asp 195 200
205 Thr Thr Pro Pro Thr Ile Asn Glu Pro Ala Gly Leu Val
His Lys Tyr 210 215 220
Tyr Arg Gly Asp His Val Glu Ile Thr Leu Pro Val Thr Asp Asn Thr225
230 235 240 Gly Gly Ser Gly Leu
Arg Asp Val Asn Val Asn Leu Pro Gln Gly Trp 245
250 255 Thr Lys Thr Phe Thr Ile Asn Pro Asn Asn
Asn Thr Glu Gly Thr Leu 260 265
270 Lys Leu Ile Gly Asn Ile Pro Ser Asn Glu Ala Tyr Asn Thr Thr
Tyr 275 280 285 His
Phe Asn Ile Thr Ala Thr Asp Asn Ser Gly Asn Thr Thr Asn Pro 290
295 300 Ala Lys Thr Phe Ile Leu
Asn Val Gly Lys Leu Ala Asp Asp Leu Asn305 310
315 320 Pro Val Gly Leu Ser Arg Asp Gln Leu Gln Leu
Val Thr Asp Pro Ser 325 330
335 Ser Leu Ser Asn Ser Glu Arg Glu Glu Val Lys Arg Lys Ile Ser Glu
340 345 350 Ala Asn Ala
Asn Ile Arg Ser Tyr Leu Leu Gln Asn Asn Pro Ile Leu 355
360 365 Ala Gly Val Asn Gly Asp Val Thr
Phe Tyr Tyr Arg Asp Gly Ser Val 370 375
380 Asp Val Ile Asp Ala Glu Asn Val Ile Thr Tyr Glu Pro
Glu Arg Lys385 390 395
400 Ser Ile Phe Ser Glu Asn Gly Asn Thr Asn Lys Lys Glu Ala Val Ile
405 410 415 Thr Ile Ala Arg
Gly Gln Asn Tyr Thr Ile Gly Pro Asn Leu Arg Lys 420
425 430 Tyr Phe Ser Leu Ser Asn Gly Ser Asp
Leu Pro Asn Arg Asp Phe Thr 435 440
445 Ser Ile Ser Ala Ile Gly Ser Leu Pro Ser Ser Ser Glu Ile
Ser Arg 450 455 460
Leu Asn Val Gly Asn Tyr Asn Tyr Arg Val Asn Ala Lys Asn Ala Tyr465
470 475 480 His Lys Thr Gln Gln
Glu Leu Asn Leu Lys Leu Lys Ile Val Glu Val 485
490 495 Asn Ala Pro Thr Gly Asn Asn Arg Val Tyr
Arg Val Ser Thr Tyr Asn 500 505
510 Leu Thr Asn Asp Glu Ile Asn Lys Ile Lys Gln Ala Phe Lys Ala
Ala 515 520 525 Asn
Ser Gly Leu Asn Leu Asn Asp Asn Asp Ile Thr Val Ser Asn Asn 530
535 540 Phe Asp His Arg Asn Val
Ser Ser Val Thr Val Thr Ile Arg Lys Gly545 550
555 560 Asp Leu Ile Lys Glu Phe Ser Ser Asn Leu Asn
Asn Met Asn Phe Leu 565 570
575 Arg Trp Val Asn Ile Arg Asp Asp Tyr Thr Ile Ser Trp Thr Ser Ser
580 585 590 Lys Ile Gln
Gly Arg Asn Thr Asp Gly Gly Leu Glu Trp Ser Pro Asp 595
600 605 His Lys Ser Leu Ile Tyr Lys Tyr
Asp Ala Thr Leu Gly Arg Gln Ile 610 615
620 Asn Thr Asn Asp Val Leu Thr Leu Leu Gln Ala Thr Ala
Lys Asn Ser625 630 635
640 Asn Leu Arg Ser Asn Ile Asn Ser Asn Glu Lys Gln Leu Ala Glu Arg
645 650 655 Gly Ser Asn Gly
Tyr Ser Lys Ser Ile Ile Arg Asp Asp Gly Glu Lys 660
665 670 Ser Tyr Leu Leu Asn Ser Asn Pro Ile
Gln Val Leu Asp Leu Val Glu 675 680
685 Pro Asp Asn Gly Tyr Gly Gly Arg Gln Val Ser His Ser Asn
Val Ile 690 695 700
Tyr Asn Glu Lys Asn Ser Ser Ile Val Asn Gly Gln Val Pro Glu Ala705
710 715 720 Asn Gly Ala Ser Ala
Phe Asn Ile Asp Lys Val Val Lys Ala Asn Ala 725
730 735 Ala Asn Asn Gly Ile Met Gly Val Ile Tyr
Lys Ala Gln Leu Tyr Leu 740 745
750 Ala Pro Tyr Ser Pro Lys Gly Tyr Ile Glu Lys Leu Gly Gln Asn
Leu 755 760 765 Ser
Asn Thr Asn Asn Val Ile Asn Val Tyr Phe Val Pro Ser Asp Lys 770
775 780 Val Asn Pro Ser Ile Thr
Val Gly Asn Tyr Asp His His Thr Val Tyr785 790
795 800 Ser Gly Glu Thr Phe Lys Asn Thr Ile Asn Val
Asn Asp Asn Tyr Gly 805 810
815 Leu Asn Thr Val Ala Ser Thr Ser Asp Ser Ala Ile Thr Met Thr Arg
820 825 830 Asn Asn Asn
Glu Leu Val Gly Gln Ala Pro Asn Val Thr Asn Ser Ile 835
840 845 Asn Lys Ile Val Lys Val Lys Ala
Thr Asp Lys Ser Gly Asn Glu Ser 850 855
860 Ile Val Ser Phe Thr Val Asn Ile Lys Pro Leu Asn Glu
Lys Tyr Arg865 870 875
880 Ile Thr Thr Ser Ser Ser Asn Gln Thr Pro Val Arg Ile Ser Asn Ile
885 890 895 Gln Asn Asn Ala
Asn Leu Ser Ile Glu Asp Gln Asn Arg Val Lys Ser 900
905 910 Ser Leu Ser Met Thr Lys Ile Leu Gly
Thr Arg Asn Tyr Val Asn Glu 915 920
925 Ser Asn Asn Asp Val Arg Ser Gln Val Val Ser Lys Val Asn
Arg Ser 930 935 940
Gly Asn Asn Ala Thr Val Asn Val Thr Thr Thr Phe Ser Asp Gly Thr945
950 955 960 Thr Asn Thr Ile Thr
Val Pro Val Lys His Val Leu Leu Glu Val Val 965
970 975 Pro Thr Thr Arg Thr Thr Val Arg Gly Gln
Gln Phe Pro Thr Gly Lys 980 985
990 Gly Thr Ser Pro Asn Asp Phe Phe Ser Leu Arg Thr Gly Gly Pro
Val 995 1000 1005 Asp
Ala Arg Ile Val Trp Val Asn Asn Gln Gly Pro Asp Ile Asn Ser 1010
1015 1020 Asn Gln Ile Gly Arg Asp
Leu Thr Leu His Ala Glu Ile Phe Phe Asp1025 1030
1035 1040Gly Glu Thr Thr Pro Ile Arg Lys Asp Thr Thr
Tyr Lys Leu Ser Gln 1045 1050
1055 Ser Ile Pro Lys Gln Ile Tyr Glu Thr Thr Ile Asn Gly Arg Phe Asn
1060 1065 1070 Ser Ser Gly
Asp Ala Tyr Pro Gly Asn Phe Val Gln Ala Val Asn Gln 1075
1080 1085 Tyr Trp Pro Glu His Met Asp Phe
Arg Trp Ala Gln Gly Ser Gly Thr 1090 1095
1100 Pro Ser Ser Arg Asn Ala Gly Ser Phe Thr Lys Thr Val
Thr Val Val1105 1110 1115
1120Tyr Gln Asn Gly Gln Thr Glu Asn Val Asn Val Leu Phe Lys Val Lys
1125 1130 1135 Pro Asn Lys Pro
Val Ile Asp Ser Asn Ser Val Ile Ser Lys Gly Gln 1140
1145 1150 Leu Asn Gly Gln Gln Ile Leu Val Arg
Asn Val Pro Gln Asn Ala Gln 1155 1160
1165 Val Thr Leu Tyr Gln Ser Asn Gly Thr Val Ile Pro Asn Thr
Asn Thr 1170 1175 1180
Thr Ile Asp Ser Asn Gly Ile Ala Thr Val Thr Ile Gln Gly Thr Leu1185
1190 1195 1200Pro Thr Gly Asn Ile
Thr Ala Lys Thr Ser Met Thr Asn Asn Val Thr 1205
1210 1215 Tyr Thr Lys Gln Asn Ser Ser Gly Ile Ala
Ser Asn Thr Thr Glu Asp 1220 1225
1230 Ile Ser Val Phe Ser Glu Asn Ser Asp Gln Val Asn Val Thr Ala
Gly 1235 1240 1245 Met
Gln Ala Lys Asn Asp Gly Ile Lys Ile Ile Lys Gly Thr Asn Tyr 1250
1255 1260 Asn Phe Asn Asp Phe Asn
Ser Phe Ile Ser Asn Ile Pro Ala His Ser1265 1270
1275 1280Thr Leu Thr Trp Asn Glu Glu Pro Asn Ser Trp
Lys Asn Asn Ile Gly 1285 1290
1295 Thr Thr Thr Lys Thr Val Thr Val Thr Leu Pro Asn His Gln Gly Thr
1300 1305 1310 Arg Thr Val
Asp Ile Pro Ile Thr Ile Tyr Pro Thr Val Thr Ala Lys 1315
1320 1325 Asn Pro Val Arg Asp Gln Lys Gly
Arg Asn Leu Thr Asn Gly Thr Asp 1330 1335
1340 Val Tyr Asn Tyr Ile Ile Phe Glu Asn Asn Asn Arg Leu
Gly Gly Thr1345 1350 1355
1360Ala Ser Trp Lys Asp Asn Arg Gln Pro Asp Lys Asn Ile Ala Gly Val
1365 1370 1375 Gln Asn Leu Ile
Ala Leu Val Asn Tyr Pro Gly Ile Ser Thr Pro Leu 1380
1385 1390 Glu Val Pro Val Lys Val Trp Val Tyr
Asn Phe Asp Phe Thr Gln Pro 1395 1400
1405 Ile Tyr Lys Ile Gln Val Gly Asp Thr Phe Pro Lys Gly Thr
Trp Ala 1410 1415 1420
Gly Tyr Tyr Lys His Leu Glu Asn Gly Glu Gly Leu Pro Ile Asp Gly1425
1430 1435 1440Trp Lys Phe Tyr Trp
Asn Gln Gln Ser Thr Gly Thr Thr Ser Asp Gln 1445
1450 1455 Trp Gln Ser Leu Ala Tyr Thr Arg Thr Pro
Phe Val Lys Thr Gly Thr 1460 1465
1470 Tyr Asp Val Val Asn Pro Ser Asn Trp Gly Val Trp Gln Thr Ser
Gln 1475 1480 1485 Ser
Ala Lys Phe Ile Val Thr Asn Ala Lys Pro Asn Gln Pro Thr Ile 1490
1495 1500 Thr Gln Ser Lys Thr Gly
Asp Val Thr Val Thr Pro Gly Ala Val Arg1505 1510
1515 1520Asn Ile Leu Ile Ser Gly Thr Asn Asp Tyr Ile
Gln Ala Ser Ala Asp 1525 1530
1535 Lys Ile Val Ile Asn Lys Asn Gly Asn Lys Leu Thr Thr Phe Val Lys
1540 1545 1550 Asn Asn Asp
Gly Arg Trp Thr Val Glu Thr Gly Ser Pro Asp Ile Asn 1555
1560 1565 Gly Ile Gly Pro Thr Asn Asn Gly
Thr Ala Ile Ser Leu Ser Arg Leu 1570 1575
1580 Ala Val Arg Pro Gly Asp Ser Ile Glu Ala Ile Ala Thr
Glu Gly Ser1585 1590 1595
1600Gly Glu Thr Ile Ser Thr Ser Ala Thr Ser Glu Ile Tyr Ile Val Lys
1605 1610 1615 Ala Pro Gln Pro
Glu Gln Val Ala Thr His Thr Tyr Asp Asn Gly Thr 1620
1625 1630 Phe Asp Ile Leu Pro Asp Asn Ser Arg
Asn Ser Leu Asn Pro Thr Glu 1635 1640
1645 Arg Val Glu Ile Asn Tyr Thr Glu Lys Leu Asn Gly Asn Glu
Thr Gln 1650 1655 1660
Lys Ser Phe Thr Ile Thr Lys Asn Asn Asn Gly Lys Trp Thr Ile Asn1665
1670 1675 1680Asn Lys Pro Asn Tyr
Val Glu Phe Asn Gln Asp Asn Gly Lys Val Val 1685
1690 1695 Phe Ser Ala Asn Thr Ile Lys Pro Asn Ser
Gln Ile Thr Ile Thr Pro 1700 1705
1710 Lys Ala Gly Gln Gly Asn Thr Glu Asn Thr Asn Pro Thr Val Ile
Gln 1715 1720 1725 Ala
Pro Ala Gln His Thr Leu Thr Ile Asn Glu Ile Val Lys Glu Gln 1730
1735 1740 Gly Gln Asn Val Thr Asn
Asp Asp Ile Asn Asn Ala Val Gln Val Pro1745 1750
1755 1760Asn Lys Asn Arg Val Ala Ile Lys Gln Gly Asn
Ala Leu Pro Thr Asn 1765 1770
1775 Leu Ala Gly Gly Ser Thr Ser His Ile Pro Val Val Ile Tyr Tyr Ser
1780 1785 1790 Asp Gly Ser
Ser Glu Glu Ala Thr Glu Thr Val Arg Thr Lys Val Asn 1795
1800 1805 Lys Thr Glu Leu Ile Asn Ala Arg
Arg Arg Leu Asp Glu Glu Ile Ser 1810 1815
1820 Lys Glu Asn Lys Thr Pro Ser Ser Ile Arg Asn Phe Asp
Gln Ala Met1825 1830 1835
1840Asn Arg Ala Gln Ser Gln Ile Asn Thr Ala Lys Ser Asp Ala Asp Gln
1845 1850 1855 Val Ile Gly Thr
Glu Phe Ala Thr Pro Gln Gln Val Asn Ser Ala Leu 1860
1865 1870 Ser Lys Val Gln Ala Ala Gln Asn Lys
Ile Asn Glu Ala Lys Ala Leu 1875 1880
1885 Leu Gln Asn Lys Ala Asp Asn Ser Gln Leu Val Arg Ala Lys
Glu Gln 1890 1895 1900
Leu Gln Gln Ser Ile Gln Pro Ala Ala Ser Thr Asp Gly Met Thr Gln1905
1910 1915 1920Asp Ser Thr Arg Asn
Tyr Asn Asn Lys Arg Gln Ala Ala Glu Gln Ala 1925
1930 1935 Ile Gln His Ala Asn Ser Val Ile Asn Asn
Gly Asp Ala Thr Ser Gln 1940 1945
1950 Gln Ile Asn Asp Ala Lys Asn Thr Val Glu Gln Ala Gln Arg Asp
Tyr 1955 1960 1965 Val
Glu Ala Lys Ser Asn Leu Arg Ala Asp Lys Ser Gln Leu Gln Ser 1970
1975 1980 Ala Tyr Asp Thr Leu Asn
Arg Asp Val Leu Thr Asn Asp Lys Lys Pro1985 1990
1995 2000Ala Ser Val Arg Arg Tyr Asn Glu Ala Ile Ser
Asn Ile Arg Lys Glu 2005 2010
2015 Leu Asp Thr Ala Lys Ala Asp Ala Ser Ser Thr Leu Arg Asn Thr Asn
2020 2025 2030 Pro Ser Val
Glu Gln Val Arg Asp Ala Leu Asn Lys Ile Asn Thr Val 2035
2040 2045 Gln Pro Lys Val Asn Gln Ala Ile
Ala Leu Leu Gln Pro Lys Glu Asn 2050 2055
2060 Asn Ser Glu Leu Val Gln Ala Lys Lys Arg Leu Gln Asp
Ala Val Asn2065 2070 2075
2080Asp Ile Pro Gln Thr Gln Gly Met Thr Gln Gln Thr Ile Asn Asn Tyr
2085 2090 2095 Asn Asp Lys Gln
Arg Glu Ala Glu Arg Ala Leu Thr Ser Ala Gln Arg 2100
2105 2110 Val Ile Asp Asn Gly Asp Ala Thr Thr
Gln Glu Ile Thr Ser Glu Lys 2115 2120
2125 Ser Lys Val Glu Gln Ala Met Gln Ala Leu Thr Asn Ala Lys
Ser Asn 2130 2135 2140
Leu Arg Ala Asp Lys Asn Glu Leu Gln Thr Ala Tyr Asn Lys Leu Ile2145
2150 2155 2160Glu Asn Val Ser Thr
Asn Gly Lys Lys Pro Ala Ser Ile Arg Gln Tyr 2165
2170 2175 Glu Thr Ala Lys Ala Arg Ile Gln Asn Gln
Ile Asn Asp Ala Lys Asn 2180 2185
2190 Glu Ala Glu Arg Ile Leu Gly Asn Asp Asn Pro Gln Val Ser Gln
Val 2195 2200 2205 Thr
Gln Ala Leu Asn Lys Ile Lys Ala Ile Gln Pro Lys Leu Thr Glu 2210
2215 2220 Ala Ile Asn Met Leu Gln
Asn Lys Glu Asn Asn Thr Glu Leu Val Asn2225 2230
2235 2240Ala Lys Asn Arg Leu Glu Asn Ala Val Asn Asp
Thr Asp Pro Thr His 2245 2250
2255 Gly Met Thr Gln Glu Thr Ile Asn Asn Tyr Asn Ala Lys Lys Arg Glu
2260 2265 2270 Ala Gln Asn
Glu Ile Gln Lys Ala Asn Met Ile Ile Asn Asn Gly Asp 2275
2280 2285 Ala Thr Ala Gln Asp Ile Ser Ser
Glu Lys Ser Lys Val Glu Gln Val 2290 2295
2300 Leu Gln Ala Leu Gln Asn Ala Lys Asn Asp Leu Arg Ala
Asp Lys Arg2305 2310 2315
2320Glu Leu Gln Thr Ala Tyr Asn Lys Leu Ile Gln Asn Val Asn Thr Asn
2325 2330 2335 Gly Lys Lys Pro
Ser Ser Ile Gln Asn Tyr Lys Ser Ala Arg Arg Asn 2340
2345 2350 Ile Glu Asn Gln Tyr Asn Thr Ala Lys
Asn Glu Ala His Asn Val Leu 2355 2360
2365 Glu Asn Thr Asn Pro Thr Val Asn Ala Val Glu Asp Ala Leu
Arg Lys 2370 2375 2380
Ile Asn Ala Ile Gln Pro Glu Val Thr Lys Ala Ile Asn Ile Leu Gln2385
2390 2395 2400Asp Lys Glu Asp Asn
Ser Glu Leu Val Arg Ala Lys Glu Lys Leu Asp 2405
2410 2415 Gln Ala Ile Asn Ser Gln Pro Ser Leu Asn
Gly Met Thr Gln Glu Ser 2420 2425
2430 Ile Asn Asn Tyr Thr Thr Lys Arg Arg Glu Ala Gln Asn Ile Ala
Ser 2435 2440 2445 Ser
Ala Asp Thr Ile Ile Asn Asn Gly Asp Ala Ser Ile Glu Gln Ile 2450
2455 2460 Thr Glu Asn Lys Ile Arg
Val Glu Glu Ala Thr Asn Ala Leu Asn Glu2465 2470
2475 2480Ala Lys Gln His Leu Thr Ala Asp Thr Thr Ser
Leu Lys Thr Glu Val 2485 2490
2495 Arg Lys Leu Ser Arg Arg Gly Asp Thr Asn Asn Lys Lys Pro Ser Ser
2500 2505 2510 Val Ser Ala
Tyr Asn Asn Thr Ile His Ser Leu Gln Ser Glu Ile Thr 2515
2520 2525 Gln Thr Glu Asn Arg Ala Asn Thr
Ile Ile Asn Lys Pro Ile Arg Ser 2530 2535
2540 Val Glu Glu Val Asn Asn Ala Leu His Glu Val Asn Gln
Leu Asn Gln2545 2550 2555
2560Arg Leu Thr Asp Thr Ile Asn Leu Leu Gln Pro Leu Ala Asn Lys Glu
2565 2570 2575 Ser Leu Lys Glu
Ala Arg Asn Arg Leu Glu Ser Lys Ile Asn Glu Thr 2580
2585 2590 Val Gln Thr Asp Gly Met Thr Gln Gln
Ser Val Glu Asn Tyr Lys Gln 2595 2600
2605 Ala Lys Ile Lys Ala Gln Asn Glu Ser Ser Ile Ala Gln Thr
Leu Ile 2610 2615 2620
Asn Asn Gly Asp Ala Ser Asp Gln Glu Val Ser Thr Glu Ile Glu Lys2625
2630 2635 2640Leu Asn Gln Lys Leu
Ser Glu Leu Thr Asn Ser Ile Asn His Leu Thr 2645
2650 2655 Val Asn Lys Glu Pro Leu Glu Thr Ala Lys
Asn Gln Leu Gln Ala Asn 2660 2665
2670 Ile Asp Gln Lys Pro Ser Thr Asp Gly Met Thr Gln Gln Ser Val
Gln 2675 2680 2685 Ser
Tyr Glu Arg Lys Leu Gln Glu Ala Lys Asp Lys Ile Asn Ser Ile 2690
2695 2700 Asn Asn Val Leu Ala Asn
Asn Pro Asp Val Asn Ala Ile Arg Thr Asn2705 2710
2715 2720Lys Val Glu Thr Glu Gln Ile Asn Asn Glu Leu
Thr Gln Ala Lys Gln 2725 2730
2735 Gly Leu Thr Val Asp Lys Gln Pro Leu Ile Asn Ala Lys Thr Ala Leu
2740 2745 2750 Gln Gln Ser
Leu Asp Asn Gln Pro Ser Thr Thr Gly Met Thr Glu Ala 2755
2760 2765 Thr Ile Gln Asn Tyr Asn Ala Lys
Arg Gln Lys Ala Glu Gln Val Ile 2770 2775
2780 Gln Asn Ala Asn Lys Ile Ile Glu Asn Ala Gln Pro Ser
Val Gln Gln2785 2790 2795
2800Val Ser Asp Glu Lys Ser Lys Val Glu Gln Ala Leu Ser Glu Leu Asn
2805 2810 2815 Asn Ala Lys Ser
Ala Leu Arg Ala Asp Lys Gln Glu Leu Gln Gln Ala 2820
2825 2830 Tyr Asn Gln Leu Ile Gln Pro Thr Asp
Leu Asn Asn Lys Lys Pro Ala 2835 2840
2845 Ser Ile Thr Ala Tyr Asn Gln Arg Tyr Gln Gln Phe Ser Asn
Glu Leu 2850 2855 2860
Asn Ser Thr Lys Thr Asn Thr Asp Arg Ile Leu Lys Glu Gln Asn Pro2865
2870 2875 2880Ser Val Ala Asp Val
Asn Asn Ala Leu Asn Lys Val Arg Glu Val Gln 2885
2890 2895 Gln Lys Leu Asn Glu Ala Arg Ala Leu Leu
Gln Asn Lys Glu Asp Asn 2900 2905
2910 Ser Ala Leu Val Arg Ala Lys Glu Gln Leu Gln Gln Ala Val Asp
Gln 2915 2920 2925 Val
Pro Ser Thr Glu Gly Met Thr Gln Gln Thr Lys Asp Asp Tyr Asn 2930
2935 2940 Ser Lys Gln Gln Ala Ala
Gln Gln Glu Ile Ser Lys Ala Gln Gln Val2945 2950
2955 2960Ile Asp Asn Gly Asp Ala Thr Thr Gln Gln Ile
Ser Asn Ala Lys Thr 2965 2970
2975 Asn Val Glu Arg Ala Leu Glu Ala Leu Asn Asn Ala Lys Thr Gly Leu
2980 2985 2990 Arg Ala Asp
Lys Glu Glu Leu Gln Asn Ala Tyr Asn Gln Leu Thr Gln 2995
3000 3005 Asn Ile Asp Thr Ser Gly Lys Thr
Pro Ala Ser Ile Arg Lys Tyr Asn 3010 3015
3020 Glu Ala Lys Ser Arg Ile Gln Thr Gln Ile Asp Ser Ala
Lys Asn Glu3025 3030 3035
3040Ala Asn Ser Ile Leu Thr Asn Asp Asn Pro Gln Val Ser Gln Val Thr
3045 3050 3055 Ala Ala Leu Asn
Lys Ile Lys Ala Val Gln Pro Glu Leu Asp Lys Ala 3060
3065 3070 Ile Ala Met Leu Lys Asn Lys Glu Asn
Asn Asn Ala Leu Val Gln Ala 3075 3080
3085 Lys Gln Gln Leu Gln Gln Ile Val Asn Glu Val Asp Pro Thr
Gln Gly 3090 3095 3100
Met Thr Thr Asp Thr Ala Asn Asn Tyr Lys Ser Lys Lys Arg Glu Ala3105
3110 3115 3120Glu Asp Glu Ile Gln
Lys Ala Gln Gln Ile Ile Asn Asn Gly Asp Ala 3125
3130 3135 Thr Glu Gln Gln Ile Thr Asn Glu Thr Asn
Arg Val Asn Gln Ala Ile 3140 3145
3150 Asn Ala Ile Asn Lys Ala Lys Asn Asp Leu Arg Ala Asp Lys Ser
Gln 3155 3160 3165 Leu
Glu Asn Ala Tyr Asn Gln Leu Ile Gln Asn Val Asp Thr Asn Gly 3170
3175 3180 Lys Lys Pro Ala Ser Ile
Gln Gln Tyr Gln Ala Ala Arg Gln Ala Ile3185 3190
3195 3200Glu Thr Gln Tyr Asn Asn Ala Lys Ser Glu Ala
His Gln Ile Leu Glu 3205 3210
3215 Asn Ser Asn Pro Ser Val Asn Glu Val Ala Gln Ala Leu Gln Lys Val
3220 3225 3230 Glu Ala Val
Gln Leu Lys Val Asn Asp Ala Ile His Ile Leu Gln Asn 3235
3240 3245 Lys Glu Asn Asn Ser Ala Leu Val
Thr Ala Lys Asn Gln Leu Gln Gln 3250 3255
3260 Ser Val Asn Asp Gln Pro Leu Thr Thr Gly Met Thr Gln
Asp Ser Ile3265 3270 3275
3280Asn Asn Tyr Glu Ala Lys Arg Asn Glu Ala Gln Ser Ala Ile Arg Asn
3285 3290 3295 Ala Glu Ala Val
Ile Asn Asn Gly Asp Ala Thr Ala Lys Gln Ile Ser 3300
3305 3310 Asp Glu Lys Ser Lys Val Glu Gln Ala
Leu Ala His Leu Asn Asp Ala 3315 3320
3325 Lys Gln Gln Leu Thr Ala Asp Thr Thr Glu Leu Gln Thr Ala
Val Gln 3330 3335 3340
Gln Leu Asn Arg Arg Gly Asp Thr Asn Asn Lys Lys Pro Arg Ser Ile3345
3350 3355 3360Asn Ala Tyr Asn Lys
Ala Ile Gln Ser Leu Glu Thr Gln Ile Thr Ser 3365
3370 3375 Ala Lys Asp Asn Ala Asn Ala Val Ile Gln
Lys Pro Ile Arg Thr Val 3380 3385
3390 Gln Glu Val Asn Asn Ala Leu Gln Gln Val Asn Gln Leu Asn Gln
Gln 3395 3400 3405 Leu
Thr Glu Ala Ile Asn Gln Leu Gln Pro Leu Ser Asn Asn Asp Ala 3410
3415 3420 Leu Lys Ala Ala Arg Leu
Asn Leu Glu Asn Lys Ile Asn Gln Thr Val3425 3430
3435 3440Gln Thr Asp Gly Met Thr Gln Gln Ser Ile Glu
Ala Tyr Gln Asn Ala 3445 3450
3455 Lys Arg Val Ala Gln Asn Glu Ser Asn Thr Ala Leu Ala Leu Ile Asn
3460 3465 3470 Asn Gly Asp
Ala Asp Glu Gln Gln Ile Thr Thr Glu Thr Asp Arg Val 3475
3480 3485 Asn Gln Gln Thr Thr Asn Leu Thr
Gln Ala Ile Asn Gly Leu Thr Val 3490 3495
3500 Asn Lys Glu Pro Leu Glu Thr Ala Lys Thr Ala Leu Gln
Asn Asn Ile3505 3510 3515
3520Asp Gln Val Pro Ser Thr Asp Gly Met Thr Gln Gln Ser Val Ala Asn
3525 3530 3535 Tyr Asn Gln Lys
Leu Gln Ile Ala Lys Asn Glu Ile Asn Thr Ile Asn 3540
3545 3550 Asn Val Leu Ala Asn Asn Pro Asp Val
Asn Ala Ile Lys Thr Asn Lys 3555 3560
3565 Ala Glu Ala Glu Arg Ile Ser Asn Asp Leu Thr Gln Ala Lys
Asn Asn 3570 3575 3580
Leu Gln Val Asp Thr Gln Pro Leu Glu Lys Ile Lys Arg Gln Leu Gln3585
3590 3595 3600Asp Glu Ile Asp Gln
Gly Thr Asn Thr Asp Gly Met Thr Gln Asp Ser 3605
3610 3615 Val Asp Asn Tyr Asn Asp Ser Leu Ser Ala
Ala Ile Ile Glu Lys Gly 3620 3625
3630 Lys Val Asn Lys Leu Leu Lys Arg Asn Pro Thr Val Glu Gln Val
Lys 3635 3640 3645 Glu
Ser Val Ala Asn Ala Gln Gln Val Ile Gln Asp Leu Gln Asn Ala 3650
3655 3660 Arg Thr Ser Leu Val Pro
Asp Lys Thr Gln Leu Gln Glu Ala Lys Asn3665 3670
3675 3680Arg Leu Glu Asn Ser Ile Asn Gln Gln Thr Asp
Thr Asp Gly Met Thr 3685 3690
3695 Gln Asp Ser Leu Asn Asn Tyr Asn Asp Lys Leu Ala Lys Ala Arg Gln
3700 3705 3710 Asn Leu Glu
Lys Ile Ser Lys Val Leu Gly Gly Gln Pro Thr Val Ala 3715
3720 3725 Glu Ile Arg Gln Asn Thr Asp Glu
Ala Asn Ala His Lys Gln Ala Leu 3730 3735
3740 Asp Thr Ala Arg Ser Gln Leu Thr Leu Asn Arg Glu Pro
Tyr Ile Asn3745 3750 3755
3760His Ile Asn Asn Glu Ser His Leu Asn Asn Ala Gln Lys Asp Asn Phe
3765 3770 3775 Lys Ala Gln Val
Asn Ser Ala Pro Asn His Asn Thr Leu Glu Thr Ile 3780
3785 3790 Lys Asn Lys Ala Asp Thr Leu Asn Gln
Ser Met Thr Ala Leu Ser Glu 3795 3800
3805 Ser Ile Ala Asp Tyr Glu Asn Gln Lys Gln Gln Glu Asn Tyr
Leu Asp 3810 3815 3820
Ala Ser Asn Asn Lys Arg Gln Asp Tyr Asp Asn Ala Val Asn Ala Ala3825
3830 3835 3840Lys Gly Ile Leu Asn
Gln Thr Gln Ser Pro Thr Met Ser Ala Asp Val 3845
3850 3855 Ile Asp Gln Lys Ala Glu Asp Val Lys Arg
Thr Lys Thr Ala Leu Asp 3860 3865
3870 Gly Asn Gln Arg Leu Glu Val Ala Lys Gln Gln Ala Leu Asn His
Leu 3875 3880 3885 Asn
Thr Leu Asn Asp Leu Asn Asp Ala Gln Arg Gln Thr Leu Thr Asp 3890
3895 3900 Thr Ile Asn His Ser Pro
Asn Ile Asn Ser Val Asn Gln Ala Lys Glu3905 3910
3915 3920Lys Ala Asn Thr Val Asn Thr Ala Met Thr Gln
Leu Lys Gln Thr Ile 3925 3930
3935 Ala Asn Tyr Asp Asp Glu Leu His Asp Gly Asn Tyr Ile Asn Ala Asp
3940 3945 3950 Lys Asp Lys
Lys Asp Ala Tyr Asn Asn Ala Val Asn Asn Ala Lys Gln 3955
3960 3965 Leu Ile Asn Gln Ser Asp Ala Asn
Gln Ala Gln Leu Asp Pro Ala Glu 3970 3975
3980 Ile Asn Lys Val Thr Gln Arg Val Asn Thr Thr Lys Asn
Asp Leu Asn3985 3990 3995
4000Gly Asn Asp Lys Leu Ala Glu Ala Lys Arg Asp Ala Asn Thr Thr Ile
4005 4010 4015 Asp Gly Leu Thr
Tyr Leu Asn Glu Ala Gln Arg Asn Lys Ala Lys Glu 4020
4025 4030 Asn Val Gly Lys Ala Ser Thr Lys Thr
Asn Ile Thr Ser Gln Leu Gln 4035 4040
4045 Asp Tyr Asn Gln Leu Asn Ile Ala Met Gln Ala Leu Arg Asn
Ser Val 4050 4055 4060
Asn Asp Val Asn Asn Val Lys Ala Asn Ser Asn Tyr Ile Asn Glu Asp4065
4070 4075 4080Asn Gly Pro Lys Glu
Ala Tyr Asn Gln Ala Val Thr His Ala Gln Thr 4085
4090 4095 Leu Ile Asn Ala Gln Ser Asn Pro Glu Met
Ser Arg Asp Val Val Asn 4100 4105
4110 Gln Lys Thr Gln Ala Val Asn Thr Ala His Gln Asn Leu His Gly
Gln 4115 4120 4125 Gln
Lys Leu Glu Gln Ala Gln Ser Ser Ala Asn Thr Glu Ile Gly Asn 4130
4135 4140 Leu Pro Asn Leu Thr Asn
Thr Gln Lys Ala Lys Glu Lys Glu Leu Val4145 4150
4155 4160Asn Ser Lys Gln Thr Arg Thr Glu Val Gln Glu
Gln Leu Asn Gln Ala 4165 4170
4175 Lys Ser Leu Asp Ser Ser Met Gly Thr Leu Lys Ser Leu Val Ala Lys
4180 4185 4190 Gln Pro Thr
Val Gln Lys Thr Ser Val Tyr Ile Asn Glu Asp Gln Pro 4195
4200 4205 Glu Gln Ser Ala Tyr Asn Asp Ser
Ile Thr Met Gly Gln Thr Ile Ile 4210 4215
4220 Asn Lys Thr Ala Asp Pro Val Leu Asp Lys Thr Leu Val
Asp Asn Ala4225 4230 4235
4240Ile Ser Asn Ile Ser Thr Lys Glu Asn Ala Leu His Gly Glu Gln Lys
4245 4250 4255 Leu Thr Thr Ala
Lys Thr Glu Ala Ile Asn Ala Leu Asn Thr Leu Ala 4260
4265 4270 Asp Leu Asn Thr Pro Gln Lys Glu Ala
Ile Lys Thr Ala Ile Asn Thr 4275 4280
4285 Ala His Thr Arg Thr Asp Val Thr Ala Glu Gln Ser Lys Ala
Asn Gln 4290 4295 4300
Ile Asn Ser Ala Met His Thr Leu Arg Gln Asn Ile Ser Asp Asn Glu4305
4310 4315 4320Ser Val Thr Asn Glu
Ser Asn Tyr Ile Asn Ala Glu Pro Glu Lys Gln 4325
4330 4335 His Ala Phe Thr Glu Ala Leu Asn Asn Ala
Lys Glu Ile Val Asn Glu 4340 4345
4350 Gln Gln Ala Thr Leu Asp Ala Asn Ser Ile Asn Gln Lys Ala Gln
Ala 4355 4360 4365 Ile
Leu Thr Thr Lys Asn Ala Leu Asp Gly Glu Glu Gln Leu Arg Arg 4370
4375 4380 Ala Lys Glu Asn Ala Asp
Gln Glu Ile Asn Thr Leu Asn Gln Leu Thr4385 4390
4395 4400Asp Ala Gln Arg Asn Ser Glu Lys Gly Leu Val
Asn Ser Ser Gln Thr 4405 4410
4415 Arg Thr Glu Val Ala Ser Gln Leu Ala Lys Ala Lys Glu Leu Asn Lys
4420 4425 4430 Val Met Glu
Gln Leu Asn His Leu Ile Asn Gly Lys Asn Gln Met Ile 4435
4440 4445 Asn Ser Ser Lys Phe Ile Asn Glu
Asp Ala Asn Gln Gln Gln Ala Tyr 4450 4455
4460 Ser Asn Ala Ile Ala Ser Ala Glu Ala Leu Lys Asn Lys
Ser Gln Asn4465 4470 4475
4480Pro Glu Leu Asp Lys Val Thr Ile Glu Gln Ala Ile Asn Asn Ile Asn
4485 4490 4495 Ser Ala Ile Asn
Asn Leu Asn Gly Glu Ala Lys Leu Thr Lys Ala Lys 4500
4505 4510 Glu Asp Ala Val Ala Ser Ile Asn Asn
Leu Ser Gly Leu Thr Asn Glu 4515 4520
4525 Gln Lys Thr Lys Glu Asn Gln Ala Val Asn Gly Ala Gln Thr
Arg Asp 4530 4535 4540
Gln Val Ala Asn Lys Leu Arg Asp Ala Glu Ala Leu Asp Gln Ser Met4545
4550 4555 4560Gln Thr Leu Arg Asp
Leu Val Asn Asn Gln Asn Ala Ile His Ser Thr 4565
4570 4575 Ser Asn Tyr Phe Asn Glu Asp Ser Thr Gln
Lys Asn Thr Tyr Asp Asn 4580 4585
4590 Ala Ile Asp Asn Gly Ser Thr Tyr Ile Thr Gly Gln His Asn Pro
Glu 4595 4600 4605 Leu
Asn Lys Ser Thr Ile Asp Gln Thr Ile Ser Arg Ile Asn Thr Ala 4610
4615 4620 Lys Asn Asp Leu His Gly
Val Glu Lys Leu Gln Arg Asp Lys Gly Thr4625 4630
4635 4640Ala Asn Gln Glu Ile Gly Gln Leu Gly Tyr Leu
Asn Asp Pro Gln Lys 4645 4650
4655 Ser Gly Glu Glu Ser Leu Val Asn Gly Ser Asn Thr Arg Ser Glu Val
4660 4665 4670 Glu Glu His
Leu Asn Glu Ala Lys Ser Leu Asn Asn Ala Met Lys Gln 4675
4680 4685 Leu Arg Asp Lys Val Ala Glu Lys
Thr Asn Val Lys Gln Ser Ser Asp 4690 4695
4700 Tyr Ile Asn Asp Ser Thr Glu His Gln Arg Gly Tyr Asp
Gln Ala Leu4705 4710 4715
4720Gln Glu Ala Glu Asn Ile Ile Asn Glu Ile Gly Asn Pro Thr Leu Asn
4725 4730 4735 Lys Ser Glu Ile
Glu Gln Lys Leu Gln Gln Leu Thr Asp Ala Gln Asn 4740
4745 4750 Ala Leu Gln Gly Ser His Leu Leu Glu
Glu Ala Lys Asn Asn Ala Ile 4755 4760
4765 Thr Gly Ile Asn Lys Leu Thr Ala Leu Asn Asp Ala Gln Arg
Gln Lys 4770 4775 4780
Ala Ile Glu Asn Val Gln Ala Gln Gln Thr Ile Pro Ala Val Asn Gln4785
4790 4795 4800Gln Leu Thr Leu Asp
Arg Glu Ile Asn Thr Ala Met Gln Ala Leu Arg 4805
4810 4815 Asp Lys Val Gly Gln Gln Asn Asn Val His
Gln Gln Ser Asn Tyr Phe 4820 4825
4830 Asn Glu Asp Glu Gln Pro Lys His Asn Tyr Asp Asn Ser Val Gln
Ala 4835 4840 4845 Gly
Gln Thr Ile Ile Asp Lys Leu Gln Asp Pro Ile Met Asn Lys Asn 4850
4855 4860 Glu Ile Glu Gln Ala Ile
Asn Gln Ile Asn Thr Thr Gln Thr Ala Leu4865 4870
4875 4880Ser Gly Glu Asn Lys Leu His Thr Asp Gln Glu
Ser Thr Asn Arg Gln 4885 4890
4895 Ile Glu Gly Leu Ser Ser Leu Asn Thr Ala Gln Ile Asn Ala Glu Lys
4900 4905 4910 Asp Leu Val
Asn Gln Ala Lys Thr Arg Thr Asp Val Ala Gln Lys Leu 4915
4920 4925 Ala Ala Ala Lys Glu Ile Asn Ser
Ala Met Ser Asn Leu Arg Asp Gly 4930 4935
4940 Ile Gln Asn Lys Glu Asp Ile Lys Arg Ser Ser Ala Tyr
Ile Asn Ala4945 4950 4955
4960Asp Pro Thr Lys Val Thr Ala Tyr Asp Gln Ala Leu Gln Asn Ala Glu
4965 4970 4975 Asn Ile Ile Asn
Ala Thr Pro Asn Val Glu Leu Asn Lys Ala Thr Ile 4980
4985 4990 Glu Gln Ala Leu Ser Arg Val Gln Gln
Ala Gln Gln Asp Leu Asp Gly 4995 5000
5005 Val Gln Gln Leu Ala Asn Ala Lys Gln Gln Ala Thr Gln Thr
Val Asn 5010 5015 5020
Gly Leu Asn Ser Leu Asn Asp Gly Gln Lys Arg Glu Leu Asn Leu Leu5025
5030 5035 5040Ile Asn Ser Ala Asn
Thr Arg Thr Lys Val Gln Glu Glu Leu Asn Lys 5045
5050 5055 Ala Thr Glu Leu Asn His Ala Met Glu Ala
Leu Arg Asn Ser Val Gln 5060 5065
5070 Asn Val Asp Gln Val Lys Gln Ser Ser Asn Tyr Val Asn Glu Asp
Gln 5075 5080 5085 Pro
Glu Gln His Asn Tyr Asp Asn Ala Val Asn Glu Ala Gln Ala Thr 5090
5095 5100 Ile Asn Asn Asn Ala Gln
Pro Val Leu Asp Lys Leu Ala Ile Glu Arg5105 5110
5115 5120Leu Thr Gln Thr Val Asn Thr Thr Lys Asp Ala
Leu His Gly Ala Gln 5125 5130
5135 Lys Leu Thr Gln Asp Gln Gln Ala Ala Glu Thr Gly Ile Arg Gly Leu
5140 5145 5150 Thr Ser Leu
Asn Glu Pro Gln Lys Asn Ala Glu Val Ala Lys Val Thr 5155
5160 5165 Ala Ala Thr Thr Arg Asp Glu Val
Arg Asn Ile Arg Gln Glu Ala Thr 5170 5175
5180 Thr Leu Asp Thr Ala Met Leu Gly Leu Arg Lys Ser Ile
Lys Asp Lys5185 5190 5195
5200Asn Asp Thr Lys Asn Ser Ser Lys Tyr Ile Asn Glu Asp His Asp Gln
5205 5210 5215 Gln Gln Ala Tyr
Asp Asn Ala Val Asn Asn Ala Gln Gln Val Ile Asp 5220
5225 5230 Glu Thr Gln Ala Thr Leu Ser Ser Asp
Thr Ile Asn Gln Leu Ala Asn 5235 5240
5245 Ala Val Thr Gln Ala Lys Ser Asn Leu His Gly Asp Thr Lys
Leu Gln 5250 5255 5260
His Asp Lys Asp Ser Ala Lys Gln Thr Ile Ala Gln Leu Gln Asn Leu5265
5270 5275 5280Asn Ser Ala Gln Lys
His Met Glu Asp Ser Leu Ile Asp Asn Glu Ser 5285
5290 5295 Thr Arg Thr Gln Val Gln His Asp Leu Thr
Glu Ala Gln Ala Leu Asp 5300 5305
5310 Gly Leu Met Gly Ala Leu Lys Glu Ser Ile Lys Asp Tyr Thr Asn
Ile 5315 5320 5325 Val
Ser Asn Gly Asn Tyr Ile Asn Ala Glu Pro Ser Lys Lys Gln Ala 5330
5335 5340 Tyr Asp Ala Ala Val Gln
Asn Ala Gln Asn Ile Ile Asn Gly Thr Asn5345 5350
5355 5360Gln Pro Thr Ile Asn Lys Gly Asn Val Thr Thr
Ala Thr Gln Thr Val 5365 5370
5375 Lys Asn Thr Lys Asp Ala Leu Asp Gly Asp His Arg Leu Glu Glu Ala
5380 5385 5390 Lys Asn Asn
Ala Asn Gln Thr Ile Arg Asn Leu Ser Asn Leu Asn Asn 5395
5400 5405 Ala Gln Lys Asp Ala Glu Lys Asn
Leu Val Asn Ser Ala Ser Thr Leu 5410 5415
5420 Glu Gln Val Gln Gln Asn Leu Gln Thr Ala Gln Gln Leu
Asp Asn Ala5425 5430 5435
5440Met Gly Glu Leu Arg Gln Ser Ile Ala Lys Lys Asp Gln Val Lys Ala
5445 5450 5455 Asp Ser Lys Tyr
Leu Asn Glu Asp Pro Gln Ile Lys Gln Asn Tyr Asp 5460
5465 5470 Asp Ala Val Gln Arg Val Glu Thr Ile
Ile Asn Glu Thr Gln Asn Pro 5475 5480
5485 Glu Leu Leu Lys Ala Asn Ile Asp Gln Ala Thr Gln Ser Val
Gln Asn 5490 5495 5500
Ala Glu Gln Ala Leu His Gly Ala Glu Lys Leu Asn Gln Asp Lys Gln5505
5510 5515 5520Thr Ser Ser Thr Glu
Leu Asp Gly Leu Thr Asp Leu Thr Asp Ala Gln 5525
5530 5535 Arg Glu Lys Leu Arg Glu Gln Ile Asn Thr
Ser Asn Ser Arg Asp Asp 5540 5545
5550 Ile Lys Gln Lys Ile Glu Gln Ala Lys Ala Leu Asn Asp Ala Met
Lys 5555 5560 5565 Lys
Leu Lys Glu Gln Val Ala Gln Lys Asp Gly Val His Ala Asn Ser 5570
5575 5580 Asp Tyr Thr Asn Glu Asp
Ser Ala Gln Lys Asp Ala Tyr Asn Asn Ala5585 5590
5595 5600Leu Lys Gln Ala Glu Asp Ile Ile Asn Asn Ser
Ser Asn Pro Asn Leu 5605 5610
5615 Asn Ala Gln Asp Ile Thr Asn Ala Leu Asn Asn Ile Lys Gln Ala Gln
5620 5625 5630 Asp Asn Leu
His Gly Ala Gln Lys Leu Gln Gln Asp Lys Asn Thr Thr 5635
5640 5645 Asn Gln Ala Ile Gly Asn Leu Asn
His Leu Asn Gln Pro Gln Lys Asp 5650 5655
5660 Ala Leu Ile Gln Ala Ile Asn Gly Ala Thr Ser Arg Asp
Gln Val Ala5665 5670 5675
5680Glu Lys Leu Lys Glu Ala Glu Ala Leu Asp Glu Ala Met Lys Gln Leu
5685 5690 5695 Glu Asp Gln Val
Asn Gln Asp Asp Gln Ile Ser Asn Ser Ser Pro Phe 5700
5705 5710 Ile Asn Glu Asp Ser Asp Lys Gln Lys
Thr Tyr Asn Asp Lys Ile Gln 5715 5720
5725 Ala Ala Lys Glu Ile Ile Asn Gln Thr Ser Asn Pro Thr Leu
Asp Lys 5730 5735 5740
Gln Lys Ile Ala Asp Thr Leu Gln Asn Ile Lys Asp Ala Val Asn Asn5745
5750 5755 5760Leu His Gly Asp Gln
Lys Leu Ala Gln Ser Lys Gln Asp Ala Asn Asn 5765
5770 5775 Gln Leu Asn His Leu Asp Asp Leu Thr Glu
Glu Gln Lys Asn His Phe 5780 5785
5790 Lys Pro Leu Ile Asn Asn Ala Asp Thr Arg Asp Glu Val Asn Lys
Gln 5795 5800 5805 Leu
Glu Ile Ala Lys Gln Leu Asn Gly Asp Met Ser Thr Leu His Lys 5810
5815 5820 Val Ile Asn Asp Lys Asp
Gln Ile Gln His Leu Ser Asn Tyr Ile Asn5825 5830
5835 5840Ala Asp Asn Asp Lys Lys Gln Asn Tyr Asp Asn
Ala Ile Lys Glu Ala 5845 5850
5855 Glu Asp Leu Ile His Asn His Pro Asp Thr Leu Asp His Lys Ala Leu
5860 5865 5870 Gln Asp Leu
Leu Asn Lys Ile Asp Gln Ala His Asn Glu Leu Asn Gly 5875
5880 5885 Glu Ser Arg Phe Lys Gln Ala Leu
Asp Asn Ala Leu Asn Asp Ile Asp 5890 5895
5900 Ser Leu Asn Ser Leu Asn Val Pro Gln Arg Gln Thr Val
Lys Asp Asn5905 5910 5915
5920Ile Asn His Val Thr Thr Leu Glu Ser Leu Ala Gln Glu Leu Gln Lys
5925 5930 5935 Ala Lys Glu Leu
Asn Asp Ala Met Lys Ala Met Arg Asp Ser Ile Met 5940
5945 5950 Asn Gln Glu Gln Ile Arg Lys Asn Ser
Asn Tyr Thr Asn Glu Asp Leu 5955 5960
5965 Ala Gln Gln Asn Ala Tyr Asn His Ala Val Asp Lys Ile Asn
Asn Ile 5970 5975 5980
Ile Gly Glu Asp Asn Ala Thr Met Asp Pro Gln Ile Ile Lys Gln Ala5985
5990 5995 6000Thr Gln Asp Ile Asn
Thr Ala Ile Asn Gly Leu Asn Gly Asp Gln Lys 6005
6010 6015 Leu Gln Asp Ala Lys Thr Asp Ala Lys Gln
Gln Ile Thr Asn Phe Thr 6020 6025
6030 Gly Leu Thr Glu Pro Gln Lys Gln Ala Leu Glu Asn Ile Ile Asn
Gln 6035 6040 6045 Gln
Thr Ser Arg Ala Asn Val Ala Lys Gln Leu Ser His Ala Lys Phe 6050
6055 6060 Leu Asn Gly Lys Met Glu
Glu Leu Lys Val Ala Val Ala Lys Ala Ser6065 6070
6075 6080Leu Val Arg Gln Asn Ser Asn Tyr Ile Asn Glu
Asp Val Ser Glu Lys 6085 6090
6095 Glu Ala Tyr Glu Gln Ala Ile Ala Lys Gly Gln Glu Ile Ile Asn Ser
6100 6105 6110 Glu Asn Asn
Pro Thr Ile Ser Ser Thr Asp Ile Asn Arg Thr Ile Gln 6115
6120 6125 Glu Ile Asn Asp Ala Glu Gln Asn
Leu His Gly Asp Asn Lys Leu Arg 6130 6135
6140 Gln Ala Gln Glu Ile Ala Lys Asn Glu Ile Gln Asn Leu
Asp Gly Leu6145 6150 6155
6160Asn Ser Ala Gln Ile Thr Lys Leu Ile Gln Asp Ile Gly Arg Thr Thr
6165 6170 6175 Thr Lys Pro Ala
Val Thr Gln Lys Leu Glu Glu Ala Lys Ala Ile Asn 6180
6185 6190 Gln Ala Met Gln Gln Leu Lys Gln Ser
Ile Ala Asp Lys Asp Ala Thr 6195 6200
6205 Leu Asn Ser Ser Asn Tyr Leu Asn Glu Asp Ser Glu Lys Lys
Leu Ala 6210 6215 6220
Tyr Asp Asn Ala Val Ser Gln Ala Glu Gln Leu Ile Asn Gln Leu Asn6225
6230 6235 6240Asp Pro Thr Met Asp
Ile Ser Asn Ile Gln Ala Ile Thr Gln Lys Val 6245
6250 6255 Ile Gln Ala Lys Asp Ser Leu His Gly Ala
Asn Lys Leu Ala Gln Asn 6260 6265
6270 Gln Ala Asp Ser Asn Leu Ile Ile Asn Gln Ser Thr Asn Leu Asn
Asp 6275 6280 6285 Lys
Gln Lys Gln Ala Leu Asn Asp Leu Ile Asn His Ala Gln Thr Lys 6290
6295 6300 Gln Gln Val Ala Glu Ile
Ile Ala Gln Ala Asn Lys Leu Asn Asn Glu6305 6310
6315 6320Met Gly Thr Leu Lys Thr Leu Val Glu Glu Gln
Ser Asn Val His Gln 6325 6330
6335 Gln Ser Lys Tyr Ile Asn Glu Asp Pro Gln Val Gln Asn Ile Tyr Asn
6340 6345 6350 Asp Ser Ile
Gln Lys Gly Arg Glu Ile Leu Asn Gly Thr Thr Asp Asp 6355
6360 6365 Val Leu Asn Asn Asn Lys Ile Ala
Asp Ala Ile Gln Asn Ile His Leu 6370 6375
6380 Thr Lys Asn Asp Leu His Gly Asp Gln Lys Leu Gln Lys
Ala Gln Gln6385 6390 6395
6400Asp Ala Thr Asn Glu Leu Asn Tyr Leu Thr Asn Leu Asn Asn Ser Gln
6405 6410 6415 Arg Gln Ser Glu
His Asp Glu Ile Asn Ser Ala Pro Ser Arg Thr Glu 6420
6425 6430 Val Ser Asn Asp Leu Asn His Ala Lys
Ala Leu Asn Glu Ala Met Arg 6435 6440
6445 Gln Leu Glu Asn Glu Val Ala Leu Glu Asn Ser Val Lys Lys
Leu Ser 6450 6455 6460
Asp Phe Ile Asn Glu Asp Glu Ala Ala Gln Asn Glu Tyr Ser Asn Ala6465
6470 6475 6480Leu Gln Lys Ala Lys
Asp Ile Ile Asn Gly Val Pro Ser Ser Thr Leu 6485
6490 6495 Asp Lys Ala Thr Ile Glu Asp Ala Leu Leu
Glu Leu Gln Asn Ala Arg 6500 6505
6510 Glu Ser Leu His Gly Glu Gln Lys Leu Gln Glu Ala Lys Asn Gln
Ala 6515 6520 6525 Val
Ala Glu Ile Asp Asn Leu Gln Ala Leu Asn Pro Gly Gln Val Leu 6530
6535 6540 Ala Glu Lys Thr Leu Val
Asn Gln Ala Ser Thr Lys Pro Glu Val Gln6545 6550
6555 6560Glu Ala Leu Gln Lys Ala Lys Glu Leu Asn Glu
Ala Met Lys Ala Leu 6565 6570
6575 Lys Thr Glu Ile Asn Lys Lys Glu Gln Ile Lys Ala Asp Ser Arg Tyr
6580 6585 6590 Val Asn Ala
Asp Ser Gly Leu Gln Ala Asn Tyr Asn Ser Ala Leu Asn 6595
6600 6605 Tyr Gly Ser Gln Ile Ile Ala Thr
Thr Gln Pro Pro Glu Leu Asn Lys 6610 6615
6620 Asp Val Ile Asn Arg Ala Thr Gln Thr Ile Lys Thr Ala
Glu Asn Asn6625 6630 6635
6640Leu Asn Gly Gln Ser Lys Leu Ala Glu Ala Lys Ser Asp Gly Asn Gln
6645 6650 6655 Ser Ile Glu His
Leu Gln Gly Leu Thr Gln Ser Gln Lys Asp Lys Gln 6660
6665 6670 His Asp Leu Ile Asn Gln Ala Gln Thr
Lys Gln Gln Val Asp Asp Ile 6675 6680
6685 Val Asn Asn Ser Lys Gln Leu Asp Asn Ser Met Asn Gln Leu
Gln Gln 6690 6695 6700
Ile Val Asn Asn Asp Asn Thr Val Lys Gln Asn Ser Asp Phe Ile Asn6705
6710 6715 6720Glu Asp Ser Ser Gln
Gln Asp Ala Tyr Asn His Ala Ile Gln Ala Ala 6725
6730 6735 Lys Asp Leu Ile Thr Ala His Pro Thr Ile
Met Asp Lys Asn Gln Ile 6740 6745
6750 Asp Gln Ala Ile Glu Asn Ile Lys Gln Ala Leu Asn Asp Leu His
Gly 6755 6760 6765 Ser
Asn Lys Leu Ser Glu Asp Lys Lys Glu Ala Ser Glu Gln Leu Gln 6770
6775 6780 Asn Leu Asn Ser Leu Thr
Asn Gly Gln Lys Asp Thr Ile Leu Asn His6785 6790
6795 6800Ile Phe Ser Ala Pro Thr Arg Ser Gln Val Gly
Glu Lys Ile Ala Ser 6805 6810
6815 Ala Lys Gln Leu Asn Asn Thr Met Lys Ala Leu Arg Asp Ser Ile Ala
6820 6825 6830 Asp Asn Asn
Glu Ile Leu Gln Ser Ser Lys Tyr Phe Asn Glu Asp Ser 6835
6840 6845 Glu Gln Gln Asn Ala Tyr Asn Gln
Ala Val Asn Lys Ala Lys Asn Ile 6850 6855
6860 Ile Asn Asp Gln Pro Thr Pro Val Met Ala Asn Asp Glu
Ile Gln Ser6865 6870 6875
6880Val Leu Asn Glu Val Lys Gln Thr Lys Asp Asn Leu His Gly Asp Gln
6885 6890 6895 Lys Leu Ala Asn
Asp Lys Thr Asp Ala Gln Ala Thr Leu Asn Ala Leu 6900
6905 6910 Asn Tyr Leu Asn Gln Ala Gln Arg Gly
Asn Leu Glu Thr Lys Val Gln 6915 6920
6925 Asn Ser Asn Ser Arg Pro Glu Val Gln Lys Val Val Gln Leu
Ala Asn 6930 6935 6940
Gln Leu Asn Asp Ala Met Lys Lys Leu Asp Asp Ala Leu Thr Gly Asn6945
6950 6955 6960Asp Ala Ile Lys Gln
Thr Ser Asn Tyr Ile Asn Glu Asp Thr Ser Gln 6965
6970 6975 Gln Val Asn Phe Asp Glu Tyr Thr Asp Arg
Gly Lys Asn Ile Val Ala 6980 6985
6990 Glu Gln Thr Asn Pro Asn Met Ser Pro Thr Asn Ile Asn Thr Ile
Ala 6995 7000 7005 Asp
Lys Ile Thr Glu Ala Lys Asn Asp Leu His Gly Val Gln Lys Leu 7010
7015 7020 Lys Gln Ala Gln Gln Gln
Ser Ile Asn Thr Ile Asn Gln Met Thr Gly7025 7030
7035 7040Leu Asn Gln Ala Gln Lys Glu Gln Leu Asn Gln
Glu Ile Gln Gln Thr 7045 7050
7055 Gln Thr Arg Ser Glu Val His Gln Val Ile Asn Lys Ala Gln Ala Leu
7060 7065 7070 Asn Asp Ser
Met Asn Thr Leu Arg Gln Ser Ile Thr Asp Glu His Glu 7075
7080 7085 Val Lys Gln Thr Ser Asn Tyr Ile
Asn Glu Thr Val Gly Asn Gln Thr 7090 7095
7100 Ala Tyr Asn Asn Ala Val Asp Arg Val Lys Gln Ile Ile
Asn Gln Thr7105 7110 7115
7120Ser Asn Pro Thr Met Asn Pro Leu Glu Val Glu Arg Ala Thr Ser Asn
7125 7130 7135 Val Lys Ile Ser
Lys Asp Ala Leu His Gly Glu Arg Glu Leu Asn Asp 7140
7145 7150 Asn Lys Asn Ser Lys Thr Phe Ala Val
Asn His Leu Asp Asn Leu Asn 7155 7160
7165 Gln Ala Gln Lys Glu Ala Leu Thr His Glu Ile Glu Gln Ala
Thr Ile 7170 7175 7180
Val Ser Gln Val Asn Asn Ile Tyr Asn Lys Ala Lys Ala Leu Asn Asn7185
7190 7195 7200Asp Met Lys Lys Leu
Lys Asp Ile Val Ala Gln Gln Asp Asn Val Arg 7205
7210 7215 Gln Ser Asn Asn Tyr Ile Asn Glu Asp Ser
Thr Pro Gln Asn Met Tyr 7220 7225
7230 Asn Asp Thr Ile Asn His Ala Gln Ser Ile Ile Asp Gln Val Ala
Asn 7235 7240 7245 Pro
Thr Met Ser His Asp Glu Ile Glu Asn Ala Ile Asn Asn Ile Lys 7250
7255 7260 His Ala Ile Asn Ala Leu
Asp Gly Glu His Lys Leu Gln Gln Ala Lys7265 7270
7275 7280Glu Asn Ala Asn Leu Leu Ile Asn Ser Leu Asn
Asp Leu Asn Ala Pro 7285 7290
7295 Gln Arg Asp Ala Ile Asn Arg Leu Val Asn Glu Ala Gln Thr Arg Glu
7300 7305 7310 Lys Val Ala
Glu Gln Leu Gln Ser Ala Gln Ala Leu Asn Asp Ala Met 7315
7320 7325 Lys His Leu Arg Asn Ser Ile Gln
Asn Gln Ser Ser Val Arg Gln Glu 7330 7335
7340 Ser Lys Tyr Ile Asn Ala Ser Asp Ala Lys Lys Glu Gln
Tyr Asn His7345 7350 7355
7360Ala Val Arg Glu Val Glu Asn Ile Ile Asn Glu Gln His Pro Thr Leu
7365 7370 7375 Asp Lys Glu Ile
Ile Lys Gln Leu Thr Asp Gly Val Asn Gln Ala Asn 7380
7385 7390 Asn Asp Leu Asn Gly Val Glu Leu Leu
Asp Ala Asp Lys Gln Asn Ala 7395 7400
7405 His Gln Ser Ile Pro Thr Leu Met His Leu Asn Gln Ala Gln
Gln Asn 7410 7415 7420
Ala Leu Asn Glu Lys Ile Asn Asn Ala Val Thr Arg Thr Glu Val Ala7425
7430 7435 7440Ala Ile Ile Gly Gln
Ala Lys Leu Leu Asp His Ala Met Glu Asn Leu 7445
7450 7455 Glu Glu Ser Ile Lys Asp Lys Glu Gln Val
Lys Gln Ser Ser Asn Tyr 7460 7465
7470 Ile Asn Glu Asp Ser Asp Val Gln Glu Thr Tyr Asp Asn Ala Val
Asp 7475 7480 7485 His
Val Thr Glu Ile Leu Asn Gln Thr Val Asn Pro Thr Leu Ser Ile 7490
7495 7500 Glu Asp Ile Glu His Ala
Ile Asn Glu Val Asn Gln Ala Lys Lys Gln7505 7510
7515 7520Leu Arg Gly Lys Gln Lys Leu Tyr Gln Thr Ile
Asp Leu Ala Asp Lys 7525 7530
7535 Glu Leu Ser Lys Leu Asp Asp Leu Thr Ser Gln Gln Ser Ser Ser Ile
7540 7545 7550 Ser Asn Gln
Ile Tyr Thr Ala Lys Thr Arg Thr Glu Val Ala Gln Ala 7555
7560 7565 Ile Glu Lys Ala Lys Ser Leu Asn
His Ala Met Lys Ala Leu Asn Lys 7570 7575
7580 Val Tyr Lys Asn Ala Asp Lys Val Leu Asp Ser Ser Arg
Phe Ile Asn7585 7590 7595
7600Glu Asp Gln Pro Glu Lys Lys Ala Tyr Gln Gln Ala Ile Asn His Val
7605 7610 7615 Asp Ser Ile Ile
His Arg Gln Thr Asn Pro Glu Met Asp Pro Thr Val 7620
7625 7630 Ile Asn Ser Ile Thr His Glu Leu Glu
Thr Ala Gln Asn Asn Leu His 7635 7640
7645 Gly Asp Gln Lys Leu Ala His Ala Gln Gln Asp Ala Ala Asn
Val Ile 7650 7655 7660
Asn Gly Leu Ile His Leu Asn Val Ala Gln Arg Glu Val Met Ile Asn7665
7670 7675 7680Thr Asn Thr Asn Ala
Thr Thr Arg Glu Lys Val Ala Lys Asn Leu Asp 7685
7690 7695 Asn Ala Gln Ala Leu Asp Lys Ala Met Glu
Thr Leu Gln Gln Val Val 7700 7705
7710 Ala His Lys Asn Asn Ile Leu Asn Asp Ser Lys Tyr Leu Asn Glu
Asp 7715 7720 7725 Ser
Lys Tyr Gln Gln Gln Tyr Asp Arg Val Ile Ala Asp Ala Glu Gln 7730
7735 7740 Leu Leu Asn Gln Thr Thr
Asn Pro Thr Leu Glu Pro Tyr Lys Val Asp7745 7750
7755 7760Ile Val Lys Asp Asn Val Leu Ala Asn Glu Lys
Ile Leu Phe Gly Ala 7765 7770
7775 Glu Lys Leu Ser Tyr Asp Lys Ser Asn Ala Asn Asp Glu Ile Lys His
7780 7785 7790 Met Asn Tyr
Leu Asn Asn Ala Gln Lys Gln Ser Ile Lys Asp Met Ile 7795
7800 7805 Ser His Ala Ala Leu Arg Thr Glu
Val Lys Gln Leu Leu Gln Gln Ala 7810 7815
7820 Lys Ile Leu Asp Glu Ala Met Lys Ser Leu Glu Asp Lys
Thr Gln Val7825 7830 7835
7840Val Ile Thr Asp Thr Thr Leu Pro Asn Tyr Thr Glu Ala Ser Glu Asp
7845 7850 7855 Lys Lys Glu Lys
Val Asp Gln Thr Val Ser His Ala Gln Ala Ile Ile 7860
7865 7870 Asp Lys Ile Asn Gly Ser Asn Val Ser
Leu Asp Gln Val Arg Gln Ala 7875 7880
7885 Leu Glu Gln Leu Thr Gln Ala Ser Glu Asn Leu Asp Gly Asp
Gln Arg 7890 7895 7900
Val Glu Glu Ala Lys Val His Ala Asn Gln Thr Ile Asp Gln Leu Thr7905
7910 7915 7920His Leu Asn Ser Leu
Gln Gln Gln Thr Ala Lys Glu Ser Val Lys Asn 7925
7930 7935 Ala Thr Lys Leu Glu Glu Ile Ala Thr Val
Ser Asn Asn Ala Gln Ala 7940 7945
7950 Leu Asn Lys Val Met Gly Lys Leu Glu Gln Phe Ile Asn His Ala
Asp 7955 7960 7965 Ser
Val Glu Asn Ser Asp Asn Tyr Arg Gln Ala Asp Asp Asp Lys Ile 7970
7975 7980 Ile Ala Tyr Asp Glu Ala
Leu Glu His Gly Gln Asp Ile Gln Lys Thr7985 7990
7995 8000Asn Ala Thr Gln Asn Glu Thr Lys Gln Ala Leu
Gln Gln Leu Ile Tyr 8005 8010
8015 Ala Glu Thr Ser Leu Asn Gly Phe Glu Arg Leu Asn His Ala Arg Pro
8020 8025 8030 Arg Ala Leu
Glu Tyr Ile Lys Ser Leu Glu Lys Ile Asn Asn Ala Gln 8035
8040 8045 Lys Ser Ala Leu Glu Asp Lys Val
Thr Gln Ser His Asp Leu Leu Glu 8050 8055
8060 Leu Glu His Ile Val Asn Glu Gly Thr Asn Leu Asn Asp
Ile Met Gly8065 8070 8075
8080Glu Leu Ala Asn Ala Ile Val Asn Asn Tyr Ala Pro Thr Lys Ala Ser
8085 8090 8095 Ile Asn Tyr Ile
Asn Ala Asp Asn Leu Arg Lys Asp Asn Phe Thr Gln 8100
8105 8110 Ala Ile Asn Asn Ala Arg Asp Ala Leu
Asn Lys Thr Gln Gly Gln Asn 8115 8120
8125 Leu Asp Phe Asn Ala Ile Asp Thr Phe Lys Asp Asp Ile Phe
Lys Thr 8130 8135 8140
Lys Asp Ala Leu Asn Gly Ile Glu Arg Leu Thr Ala Ala Lys Ser Lys8145
8150 8155 8160Ala Glu Lys Leu Ile
Asp Ser Leu Lys Phe Ile Asn Lys Ala Gln Phe 8165
8170 8175 Thr His Ala Asn Asp Glu Ile Met Asn Thr
Asn Ser Ile Ala Gln Leu 8180 8185
8190 Ser Arg Ile Val Asn Gln Ala Phe Asp Leu Asn Asp Ala Met Lys
Ser 8195 8200 8205 Leu
Arg Asp Glu Leu Asn Asn Gln Ala Phe Pro Val Gln Ala Ser Ser 8210
8215 8220 Asn Tyr Ile Asn Ser Asp
Glu Asp Leu Lys Gln Gln Phe Asp His Ala8225 8230
8235 8240Leu Ser Asn Ala Arg Lys Val Leu Ala Lys Glu
Asn Gly Lys Asn Leu 8245 8250
8255 Asp Glu Lys Gln Ile Gln Gly Leu Lys Gln Val Ile Glu Asp Thr Lys
8260 8265 8270 Asp Ala Leu
Asn Gly Ile Gln Arg Leu Ser Lys Ala Lys Ala Lys Ala 8275
8280 8285 Ile Gln Tyr Val Gln Ser Leu Ser
Tyr Ile Asn Asp Ala Gln Arg His 8290 8295
8300 Ile Ala Glu Asn Asn Ile His Asn Ser Asp Asp Leu Ser
Ser Leu Ala8305 8310 8315
8320Asn Thr Leu Ser Lys Ala Ser Asp Leu Asp Asn Ala Met Lys Asp Leu
8325 8330 8335 Arg Asp Thr Ile
Glu Ser Asn Ser Thr Ser Val Pro Asn Ser Val Asn 8340
8345 8350 Tyr Ile Asn Ala Asp Lys Asn Leu Gln
Ile Glu Phe Asp Glu Ala Leu 8355 8360
8365 Gln Gln Ala Ser Ala Thr Ser Ser Lys Thr Ser Glu Asn Pro
Ala Thr 8370 8375 8380
Ile Glu Glu Val Leu Gly Leu Ser Gln Ala Ile Tyr Asp Thr Lys Asn8385
8390 8395 8400Ala Leu Asn Gly Glu
Gln Arg Leu Ala Thr Glu Lys Ser Lys Asp Leu 8405
8410 8415 Lys Leu Ile Lys Gly Leu Lys Asp Leu Asn
Lys Ala Gln Leu Glu Asp 8420 8425
8430 Val Thr Asn Lys Val Asn Ser Ala Asn Thr Leu Thr Glu Leu Ser
Gln 8435 8440 8445 Leu
Thr Gln Ser Thr Leu Glu Leu Asn Asp Lys Met Lys Leu Leu Arg 8450
8455 8460 Asp Lys Leu Lys Thr Leu
Val Asn Pro Val Lys Ala Ser Leu Asn Tyr8465 8470
8475 8480Arg Asn Ala Asp Tyr Asn Leu Lys Arg Gln Phe
Asn Lys Ala Leu Lys 8485 8490
8495 Glu Ala Lys Gly Val Leu Asn Lys Asn Ser Gly Thr Asn Val Asn Ile
8500 8505 8510 Asn Asp Ile
Gln His Leu Leu Thr Gln Ile Asp Asn Ala Lys Asp Gln 8515
8520 8525 Leu Asn Gly Glu Arg Arg Leu Lys
Glu His Gln Gln Lys Ser Glu Val 8530 8535
8540 Phe Ile Ile Lys Glu Leu Asp Ile Leu Asn Asn Ala Gln
Lys Ala Ala8545 8550 8555
8560Ile Ile Asn Gln Ile Arg Ala Ser Lys Asp Ile Lys Ile Ile Asn Gln
8565 8570 8575 Ile Val Asp Asn
Ala Ile Glu Leu Asn Asp Ala Met Gln Gly Leu Lys 8580
8585 8590 Glu His Val Ala Gln Leu Thr Ala Thr
Thr Lys Asp Asn Ile Glu Tyr 8595 8600
8605 Leu Asn Ala Asp Glu Asp His Lys Leu Gln Tyr Asp Tyr Ala
Ile Asn 8610 8615 8620
Leu Ala Asn Asn Val Leu Asp Lys Glu Asn Gly Thr Asn Lys Asp Ala8625
8630 8635 8640Asn Ile Ile Ile Gly
Met Ile Gln Asn Met Asp Asp Ala Arg Ala Leu 8645
8650 8655 Leu Asn Gly Ile Glu Arg Leu Lys Asp Ala
Gln Thr Lys Ala His Asn 8660 8665
8670 Asp Ile Lys Asp Thr Leu Lys Arg Gln Leu Asp Glu Ile Glu His
Ala 8675 8680 8685 Asn
Ala Thr Ser Asn Ser Lys Ala Gln Ala Lys Gln Met Val Asn Glu 8690
8695 8700 Glu Ala Arg Lys Ala Leu
Ser Asn Ile Asn Asp Ala Thr Ser Asn Asp8705 8710
8715 8720Leu Val Asn Gln Ala Lys Asp Glu Gly Gln Ser
Ala Ile Glu His Ile 8725 8730
8735 His Ala Asp Glu Leu Pro Lys Ala Lys Leu Asp Ala Asn Gln Met Ile
8740 8745 8750 Asp Gln Lys
Val Glu Asp Ile Asn His Leu Ile Ser Gln Asn Pro Asn 8755
8760 8765 Leu Ser Asn Glu Glu Lys Asn Lys
Leu Ile Ser Gln Ile Asn Lys Leu 8770 8775
8780 Val Asn Gly Ile Lys Asn Glu Ile Gln Gln Ala Ile Asn
Lys Gln Gln8785 8790 8795
8800Ile Glu Asn Ala Thr Thr Lys Leu Asp Glu Val Ile Glu Thr Thr Lys
8805 8810 8815 Lys Leu Ile Ile
Ala Lys Ala Glu Ala Lys Gln Met Ile Lys Glu Leu 8820
8825 8830 Ser Gln Lys Lys Arg Asp Ala Ile Asn
Asn Asn Thr Asp Leu Thr Pro 8835 8840
8845 Ser Gln Lys Ala His Ala Leu Ala Asp Ile Asp Lys Thr Glu
Lys Asp 8850 8855 8860
Ala Leu Gln His Ile Glu Asn Ser Asn Ser Ile Asp Asp Ile Asn Asn8865
8870 8875 8880Asn Lys Glu His Ala
Phe Asn Thr Leu Ala His Ile Ile Ile Trp Asp 8885
8890 8895 Thr Asp Gln Gln Pro Leu Val Phe Glu Leu
Pro Glu Leu Ser Leu Gln 8900 8905
8910 Asn Ala Leu Val Thr Ser Glu Val Val Val His Arg Asp Glu Thr
Ile 8915 8920 8925 Ser
Leu Glu Ser Ile Ile Gly Ala Met Thr Leu Thr Asp Glu Leu Lys 8930
8935 8940 Val Asn Ile Val Ser Leu
Pro Asn Thr Asp Lys Val Ala Asp His Leu8945 8950
8955 8960Thr Ala Lys Val Lys Val Ile Leu Ala Asp Gly
Ser Tyr Val Thr Val 8965 8970
8975 Asn Val Pro Val Lys Val Val Glu Lys Glu Leu Gln Ile Ala Lys Lys
8980 8985 8990 Asp Ala Ile
Lys Thr Ile Asp Val Leu Val Lys Gln Lys Ile Lys Asp 8995
9000 9005 Ile Asp Ser Asn Asn Glu Leu Thr
Ser Thr Gln Arg Glu Asp Ala Lys 9010 9015
9020 Ala Glu Ile Glu Arg Leu Lys Lys Gln Ala Ile Asp Lys
Val Asn His9025 9030 9035
9040Ser Lys Ser Ile Lys Asp Ile Glu Thr Val Lys Arg Thr Asp Phe Glu
9045 9050 9055 Glu Ile Asp Gln
Phe Asp Pro Lys Arg Phe Thr Leu Asn Lys Ala Lys 9060
9065 9070 Lys Asp Ile Ile Thr Asp Val Asn Thr
Gln Ile Gln Asn Gly Phe Lys 9075 9080
9085 Glu Ile Glu Thr Ile Lys Gly Leu Thr Ser Asn Glu Lys Thr
Gln Phe 9090 9095 9100
Asp Lys Gln Leu Thr Ala Leu Gln Lys Glu Phe Leu Glu Lys Val Glu9105
9110 9115 9120His Ala His Asn Leu
Val Glu Leu Asn Gln Leu Gln Gln Glu Phe Asn 9125
9130 9135 Asn Arg Tyr Lys His Ile Leu Asn Gln Ala
His Leu Leu Gly Glu Lys 9140 9145
9150 His Ile Ala Glu His Lys Leu Gly Tyr Val Val Val Asn Lys Thr
Gln 9155 9160 9165 Gln
Ile Leu Asn Asn Gln Ser Ala Ser Tyr Phe Ile Lys Gln Trp Ala 9170
9175 9180 Leu Asp Arg Ile Lys Gln
Ile Gln Leu Glu Thr Met Asn Ser Ile Arg9185 9190
9195 9200Gly Ala His Thr Val Gln Asp Val His Lys Ala
Leu Leu Gln Gly Ile 9205 9210
9215 Glu Gln Ile Leu Lys Val Asn Val Ser Ile Ile Asn Gln Ser Phe Asn
9220 9225 9230 Asp Ser Leu
His Asn Phe Asn Tyr Leu His Ser Lys Phe Asp Ala Arg 9235
9240 9245 Leu Arg Glu Lys Asp Val Ala Asn
His Ile Val Gln Thr Glu Thr Phe 9250 9255
9260 Lys Glu Val Leu Lys Gly Thr Gly Val Glu Pro Gly Lys
Ile Asn Lys9265 9270 9275
9280Glu Thr Gln Gln Pro Lys Leu His Lys Asn Asp Asn Asp Ser Leu Phe
9285 9290 9295 Lys His Leu Val
Asp Asn Phe Gly Lys Thr Val Gly Val Ile Thr Leu 9300
9305 9310 Thr Gly Leu Leu Ser Ser Phe Trp Leu
Val Leu Ala Lys Arg Arg Lys 9315 9320
9325 Lys Glu Glu Glu Glu Lys Gln Ser Ile Lys Asn His His Lys
Asp Ile 9330 9335 9340
Arg Leu Ser Asp Thr Asp Lys Ile Asp Pro Ile Val Ile Thr Lys Arg9345
9350 9355 9360Lys Ile Asp Lys Glu
Glu Gln Ile Gln Asn Asp Asp Lys His Ser Ile 9365
9370 9375 Pro Val Ala Lys His Lys Lys Ser Lys Glu
Lys Gln Leu Ser Glu Glu 9380 9385
9390 Asp Ile His Ser Ile Pro Val Val Lys Arg Lys Gln Asn Ser Asp
Asn 9395 9400 9405 Lys
Asp Thr Lys Gln Lys Lys Val Thr Ser Lys Lys Lys Lys Thr Pro 9410
9415 9420 Gln Ser Thr Lys Lys Val
Val Lys Thr Lys Lys Arg Ser Lys Lys9425 9430
9435 161115PRTStaphylococcus sp. 16Met Arg Asp Lys Lys
Gly Pro Val Asn Lys Arg Val Asp Phe Leu Ser1 5
10 15 Asn Lys Leu Asn Lys Tyr Ser Ile Arg Lys
Phe Thr Val Gly Thr Ala 20 25
30 Ser Ile Leu Ile Gly Ser Leu Met Tyr Leu Gly Thr Gln Gln Glu
Ala 35 40 45 Glu
Ala Ala Glu Asn Asn Ile Glu Asn Pro Thr Thr Leu Lys Asp Asn 50
55 60 Val Gln Ser Lys Glu Val
Lys Ile Glu Glu Val Thr Asn Lys Asp Thr65 70
75 80 Ala Pro Gln Gly Val Glu Ala Lys Ser Glu Val
Thr Ser Asn Lys Asp 85 90
95 Thr Ile Glu His Glu Ala Ser Val Lys Ala Glu Asp Ile Ser Lys Lys
100 105 110 Glu Asp Thr
Pro Lys Glu Val Ala Asn Val Ala Glu Val Gln Pro Lys 115
120 125 Ser Ser Val Thr His Asn Ala Glu
Ala Pro Lys Val Arg Lys Ala Arg 130 135
140 Ser Val Asp Glu Gly Ser Phe Asp Ile Thr Arg Asp Ser
Lys Asn Val145 150 155
160 Val Glu Ser Thr Pro Ile Thr Ile Gln Gly Lys Glu His Phe Glu Gly
165 170 175 Tyr Gly Ser Val
Asp Ile Gln Lys Asn Pro Thr Asp Leu Gly Val Ser 180
185 190 Glu Val Thr Arg Phe Asn Val Gly Asn
Glu Ser Asn Gly Leu Ile Gly 195 200
205 Ala Leu Gln Leu Lys Asn Lys Ile Asp Phe Ser Lys Asp Phe
Asn Phe 210 215 220
Lys Val Arg Val Ala Asn Asn His Gln Ser Asn Thr Thr Gly Ala Asp225
230 235 240 Gly Trp Gly Phe Leu
Phe Ser Lys Gly Asn Ala Glu Glu Tyr Leu Thr 245
250 255 Asn Gly Gly Ile Leu Gly Asp Lys Gly Leu
Val Asn Ser Gly Gly Phe 260 265
270 Lys Ile Asp Thr Gly Tyr Ile Tyr Thr Ser Ser Met Asp Lys Thr
Glu 275 280 285 Lys
Gln Ala Gly Gln Gly Tyr Arg Gly Tyr Gly Ala Phe Val Lys Asn 290
295 300 Asp Ser Ser Gly Asn Ser
Gln Met Val Gly Glu Asn Ile Asp Lys Ser305 310
315 320 Lys Thr Asn Phe Leu Asn Tyr Ala Asp Asn Ser
Thr Asn Thr Ser Asp 325 330
335 Gly Lys Phe His Gly Gln Arg Leu Asn Asp Val Ile Leu Thr Tyr Val
340 345 350 Ala Ser Thr
Gly Lys Met Arg Ala Glu Tyr Ala Gly Lys Thr Trp Glu 355
360 365 Thr Ser Ile Thr Asp Leu Gly Leu
Ser Lys Asn Gln Ala Tyr Asn Phe 370 375
380 Leu Ile Thr Ser Ser Gln Arg Trp Gly Leu Asn Gln Gly
Ile Asn Ala385 390 395
400 Asn Gly Trp Met Arg Thr Asp Leu Lys Gly Ser Glu Phe Thr Phe Thr
405 410 415 Pro Glu Ala Pro
Lys Thr Ile Thr Glu Leu Glu Lys Lys Val Glu Glu 420
425 430 Ile Pro Phe Lys Lys Glu Arg Lys Phe
Asn Pro Asp Leu Ala Pro Gly 435 440
445 Thr Glu Lys Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr
Ile Thr 450 455 460
Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu Ile Ile Ser Lys Gly465
470 475 480 Glu Ser Lys Glu Glu
Ile Thr Lys Asp Pro Ile Asn Glu Leu Thr Glu 485
490 495 Tyr Gly Pro Glu Thr Ile Ala Pro Gly His
Arg Asp Glu Phe Asp Pro 500 505
510 Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly
Ile 515 520 525 Lys
Asn Pro Glu Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 530
535 540 Thr Lys Tyr Gly Pro Val
Lys Gly Asp Ser Ile Val Glu Lys Glu Glu545 550
555 560 Ile Pro Phe Glu Lys Glu Arg Lys Phe Asn Pro
Asp Leu Ala Pro Gly 565 570
575 Thr Glu Lys Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr Ile Thr
580 585 590 Thr Pro Thr
Leu Lys Asn Pro Leu Thr Gly Glu Ile Ile Ser Lys Gly 595
600 605 Glu Ser Lys Glu Glu Ile Thr Lys
Asp Pro Ile Asn Glu Leu Thr Glu 610 615
620 Tyr Gly Pro Glu Thr Ile Ala Pro Gly His Arg Asp Glu
Phe Asp Pro625 630 635
640 Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly Ile
645 650 655 Lys Asn Pro Glu
Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 660
665 670 Thr Lys Tyr Gly Pro Val Lys Gly Asp
Ser Ile Val Glu Lys Glu Glu 675 680
685 Ile Pro Phe Lys Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala
Pro Gly 690 695 700
Thr Glu Lys Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr Ile Thr705
710 715 720 Thr Pro Thr Leu Lys
Asn Pro Leu Thr Gly Glu Ile Ile Ser Lys Gly 725
730 735 Glu Ser Lys Glu Glu Ile Thr Lys Asp Pro
Ile Asn Glu Leu Thr Glu 740 745
750 Tyr Gly Pro Glu Thr Ile Thr Pro Gly His Arg Asp Glu Phe Asp
Pro 755 760 765 Lys
Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly Ile 770
775 780 Lys Asn Pro Glu Thr Gly
Asp Val Val Arg Pro Pro Val Asp Ser Val785 790
795 800 Thr Lys Tyr Gly Pro Val Lys Gly Asp Ser Ile
Val Glu Lys Glu Glu 805 810
815 Ile Pro Phe Glu Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly
820 825 830 Thr Glu Lys
Val Thr Arg Glu Gly Gln Lys Gly Glu Lys Thr Ile Thr 835
840 845 Thr Pro Thr Leu Lys Asn Pro Leu
Thr Gly Glu Ile Ile Ser Lys Gly 850 855
860 Glu Ser Lys Glu Glu Ile Thr Lys Asp Pro Val Asn Glu
Leu Thr Glu865 870 875
880 Phe Gly Gly Glu Lys Ile Pro Gln Gly His Lys Asp Ile Phe Asp Pro
885 890 895 Asn Leu Pro Thr
Asp Gln Thr Glu Lys Val Pro Gly Lys Pro Gly Ile 900
905 910 Lys Asn Pro Asp Thr Gly Lys Val Ile
Glu Glu Pro Val Asp Asp Val 915 920
925 Ile Lys His Gly Pro Lys Thr Gly Thr Pro Glu Thr Lys Thr
Val Glu 930 935 940
Ile Pro Phe Glu Thr Lys Arg Glu Phe Asn Pro Lys Leu Gln Pro Gly945
950 955 960 Glu Glu Arg Val Lys
Gln Glu Gly Gln Pro Gly Ser Lys Thr Ile Thr 965
970 975 Thr Pro Ile Thr Val Asn Pro Leu Thr Gly
Glu Lys Val Gly Glu Gly 980 985
990 Gln Pro Thr Glu Glu Ile Thr Lys Gln Pro Val Asp Lys Ile Val
Glu 995 1000 1005 Phe
Gly Gly Glu Lys Pro Lys Asp Pro Lys Gly Pro Glu Asn Pro Glu 1010
1015 1020 Lys Pro Ser Arg Pro Thr
His Pro Ser Gly Pro Val Asn Pro Asn Asn1025 1030
1035 1040Pro Gly Leu Ser Lys Asp Arg Ala Lys Pro Asn
Gly Pro Val His Ser 1045 1050
1055 Met Asp Lys Asn Asp Lys Val Lys Lys Ser Lys Ile Ala Lys Glu Ser
1060 1065 1070 Val Ala Asn
Gln Glu Lys Lys Arg Ala Glu Leu Pro Lys Thr Gly Leu 1075
1080 1085 Glu Ser Thr Gln Lys Gly Leu Ile
Phe Ser Ser Ile Ile Gly Ile Ala 1090 1095
1100 Gly Leu Met Leu Leu Ala Arg Arg Arg Lys Asn1105
1110 1115171469PRTStaphylococcus sp. 17Met Gly
Lys Arg Arg Gln Gly Pro Ile Asn Lys Lys Val Asp Phe Leu1 5
10 15 Pro Asn Lys Leu Asn Lys Tyr
Ser Ile Arg Lys Phe Thr Val Gly Thr 20 25
30 Ala Ser Ile Leu Leu Gly Ser Thr Leu Ile Phe Gly
Ser Ser Ser His 35 40 45
Glu Ala Lys Ala Ala Glu Glu Lys Gln Val Asp Pro Ile Thr Gln Ala
50 55 60 Asn Gln Asn
Asp Ser Ser Glu Arg Ser Leu Glu Asn Thr Asn Gln Pro65 70
75 80 Thr Val Asn Asn Glu Ala Pro Gln
Met Ser Ser Thr Leu Gln Ala Glu 85 90
95 Glu Gly Ser Asn Ala Glu Ala Pro Asn Val Pro Thr Ile
Lys Ala Asn 100 105 110
Ser Asp Asn Asp Thr Gln Thr Gln Phe Ser Glu Ala Pro Thr Arg Asn
115 120 125 Asp Leu Ala Arg
Lys Glu Asp Ile Pro Ala Val Ser Lys Asn Glu Glu 130
135 140 Leu Gln Ser Ser Gln Pro Asn Thr
Asp Ser Lys Ile Glu Pro Thr Thr145 150
155 160 Ser Glu Pro Val Asn Leu Asn Tyr Ser Ser Pro Phe
Met Ser Leu Leu 165 170
175 Ser Met Pro Ala Asp Ser Ser Ser Asn Asn Thr Lys Asn Thr Ile Asp
180 185 190 Ile Pro Pro
Thr Thr Val Lys Gly Arg Asp Asn Tyr Asp Phe Tyr Gly 195
200 205 Arg Val Asp Ile Gln Ser Asn Pro
Thr Asp Leu Asn Ala Thr Asn Leu 210 215
220 Thr Arg Tyr Asn Tyr Gly Gln Pro Pro Gly Thr Thr Thr
Ala Gly Ala225 230 235
240 Val Gln Phe Lys Asn Gln Val Ser Phe Asp Lys Asp Phe Asp Phe Asn
245 250 255 Ile Arg Val Ala
Asn Asn Arg Gln Ser Asn Thr Thr Gly Ala Asp Gly 260
265 270 Trp Gly Phe Met Phe Ser Lys Lys Asp
Gly Asp Asp Phe Leu Lys Asn 275 280
285 Gly Gly Ile Leu Arg Glu Lys Gly Thr Pro Ser Ala Ala Gly
Phe Arg 290 295 300
Ile Asp Thr Gly Tyr Tyr Asn Asn Asp Pro Leu Asp Lys Ile Gln Lys305
310 315 320 Gln Ala Gly Gln Gly
Tyr Arg Gly Tyr Gly Thr Phe Val Lys Asn Asp 325
330 335 Ser Gln Gly Asn Thr Ser Lys Val Gly Ser
Gly Thr Pro Ser Thr Asp 340 345
350 Phe Leu Asn Tyr Ala Asp Asn Thr Thr Asn Asp Leu Asp Gly Lys
Phe 355 360 365 His
Gly Gln Lys Leu Asn Asn Val Asn Leu Lys Tyr Asn Ala Ser Asn 370
375 380 Gln Thr Phe Thr Ala Thr
Tyr Ala Gly Lys Thr Trp Thr Ala Thr Leu385 390
395 400 Ser Glu Leu Gly Leu Ser Pro Thr Asp Ser Tyr
Asn Phe Leu Val Thr 405 410
415 Ser Ser Gln Tyr Gly Asn Gly Asn Ser Gly Thr Tyr Ala Asp Gly Val
420 425 430 Met Arg Ala
Asp Leu Asp Gly Ala Thr Leu Thr Tyr Thr Pro Lys Ala 435
440 445 Val Asp Gly Asp Pro Ile Thr Ser
Thr Lys Glu Ile Pro Phe Asn Lys 450 455
460 Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu
Lys Val Val465 470 475
480 Gln Lys Gly Glu Pro Gly Ile Glu Thr Thr Thr Thr Pro Thr Tyr Val
485 490 495 Asn Pro Asn Thr
Gly Glu Lys Val Gly Glu Gly Thr Pro Thr Thr Lys 500
505 510 Ile Thr Lys Gln Pro Val Asp Glu Ile
Val His Tyr Gly Gly Glu Glu 515 520
525 Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro
Lys Gly 530 535 540
Ser Gln Thr Thr Gln Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr545
550 555 560 Gly Glu Val Val Thr
Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 565
570 575 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu
Glu Ile Pro Phe Asp Lys 580 585
590 Lys Arg Glu Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val
Lys 595 600 605 Gln
Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys 610
615 620 Asn Pro Leu Thr Gly Glu
Lys Val Gly Glu Gly Glu Pro Thr Glu Lys625 630
635 640 Ile Thr Lys Gln Pro Val Asp Glu Ile Thr Glu
Tyr Gly Gly Glu Glu 645 650
655 Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly
660 665 670 Ser Gln Glu
Asp Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 675
680 685 Gly Glu Val Val Thr Pro Pro Val
Asp Asp Val Thr Lys Tyr Gly Pro 690 695
700 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro
Phe Asp Lys705 710 715
720 Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val
725 730 735 Gln Lys Gly Glu
Pro Gly Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys 740
745 750 Asn Pro Leu Thr Gly Glu Lys Val Gly
Glu Gly Glu Pro Thr Glu Lys 755 760
765 Ile Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly
Glu Glu 770 775 780
Ile Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly785
790 795 800 Ser Gln Glu Asp Val
Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 805
810 815 Gly Glu Val Val Thr Pro Pro Val Asp Asp
Val Thr Lys Tyr Gly Pro 820 825
830 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp
Lys 835 840 845 Lys
Arg Glu Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val Lys 850
855 860 Gln Lys Gly Glu Pro Gly
Thr Lys Thr Ile Thr Thr Pro Thr Thr Lys865 870
875 880 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly
Glu Pro Thr Glu Lys 885 890
895 Val Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Glu
900 905 910 Ile Lys Pro
Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 915
920 925 Ser Gln Glu Asp Val Pro Gly Lys
Pro Gly Val Lys Asn Pro Asp Thr 930 935
940 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys
Tyr Gly Pro945 950 955
960 Val Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys
965 970 975 Lys Arg Glu Phe
Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 980
985 990 Gln Lys Gly Glu Pro Gly Thr Lys Thr
Ile Thr Thr Pro Thr Thr Lys 995 1000
1005 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr
Glu Lys 1010 1015 1020
Ile Thr Lys Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Glu1025
1030 1035 1040Ile Lys Pro Gly His
Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 1045
1050 1055 Ser Gln Thr Thr Gln Pro Gly Lys Pro Gly
Val Lys Asn Pro Asp Thr 1060 1065
1070 Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly
Pro 1075 1080 1085 Val
Asp Gly Asp Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 1090
1095 1100 Lys Arg Glu Phe Asp Pro
Asn Leu Ala Pro Gly Thr Glu Lys Val Val1105 1110
1115 1120Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr
Thr Pro Thr Thr Lys 1125 1130
1135 Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys
1140 1145 1150 Ile Thr Lys
Gln Pro Val Asp Glu Ile Val His Tyr Gly Gly Glu Gln 1155
1160 1165 Ile Pro Gln Gly His Lys Asp Glu
Phe Asp Pro Asn Ala Pro Val Asp 1170 1175
1180 Ser Lys Thr Glu Val Pro Gly Lys Pro Gly Val Lys Asn
Pro Asp Thr1185 1190 1195
1200Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro
1205 1210 1215 Lys Val Gly Asn
Pro Ile Thr Ser Thr Glu Glu Ile Pro Phe Asp Lys 1220
1225 1230 Lys Arg Val Phe Asn Pro Asp Leu Lys
Pro Gly Glu Glu Arg Val Lys 1235 1240
1245 Gln Lys Gly Glu Pro Gly Thr Lys Thr Ile Thr Thr Pro Ile
Leu Val 1250 1255 1260
Asn Pro Ile Thr Gly Glu Lys Val Gly Glu Gly Lys Ser Thr Glu Lys1265
1270 1275 1280Val Thr Lys Gln Pro
Val Asp Glu Ile Val Glu Tyr Gly Pro Thr Lys 1285
1290 1295 Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly
Lys Pro Ala Glu Pro Gly 1300 1305
1310 Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Thr Pro Ala
Glu 1315 1320 1325 Pro
Gly Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro 1330
1335 1340 Ala Glu Pro Gly Lys Pro
Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly1345 1350
1355 1360Thr Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro
Gly Lys Pro Ala Glu 1365 1370
1375 Pro Gly Lys Pro Ala Glu Pro Gly Thr Pro Ala Glu Pro Gly Lys Pro
1380 1385 1390 Ala Glu Pro
Gly Thr Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly 1395
1400 1405 Thr Pro Thr Gln Ser Gly Ala Pro
Glu Gln Pro Asn Arg Ser Met His 1410 1415
1420 Ser Thr Asp Asn Lys Asn Gln Leu Pro Asp Thr Gly Glu
Asn Arg Gln1425 1430 1435
1440Ala Asn Glu Gly Thr Leu Val Gly Ser Leu Leu Ala Ile Val Gly Ser
1445 1450 1455 Leu Phe Ile Phe
Gly Arg Arg Lys Lys Gly Asn Glu Lys 1460 1465
18167PRTStaphylococcus sp. 18Met Lys Lys Leu Tyr Thr Ser Tyr
Gly Thr Tyr Gly Phe Leu His Gln1 5 10
15 Ile Lys Ile Asn Asn Pro Thr His Gln Leu Phe Gln Phe
Ser Ala Ser 20 25 30
Asp Thr Ser Val Ile Phe Glu Glu Thr Asp Gly Glu Thr Val Leu Lys
35 40 45 Ser Pro Ser Ile
Tyr Glu Val Ile Lys Glu Ile Gly Glu Phe Ser Glu 50 55
60 His His Phe Tyr Cys Ala Ile Phe Ile
Pro Ser Thr Glu Asp His Ala65 70 75
80 Tyr Gln Leu Glu Lys Lys Leu Ile Ser Val Asp Asp Asn Phe
Arg Asn 85 90 95
Phe Gly Gly Phe Lys Ser Tyr Arg Leu Leu Arg Pro Ala Lys Gly Thr
100 105 110 Thr Tyr Lys Ile Tyr
Phe Gly Phe Ala Asp Arg His Ala Tyr Glu Asp 115
120 125 Phe Lys Gln Ser Asp Ala Phe Asn Asp
His Phe Ser Lys Asp Ala Leu 130 135
140 Ser His Tyr Phe Gly Ser Ser Gly Gln His Ser Ser Tyr
Phe Glu Arg145 150 155
160 Tyr Leu Tyr Pro Ile Lys Glu 165
19167PRTStaphylococcus sp. 19Met Tyr Leu Tyr Thr Ser Tyr Gly Thr Tyr Gln
Phe Leu Asn Gln Ile1 5 10
15 Lys Leu Asn His Gln Glu Arg Ser Leu Phe Gln Phe Ser Thr Asn Asp
20 25 30 Ser Ser Ile
Ile Leu Glu Glu Ser Glu Gly Lys Ser Ile Leu Lys His 35
40 45 Pro Ser Ala Tyr Gln Val Ile Asp
Ser Thr Gly Glu Phe Asn Glu His 50 55
60 His Phe Tyr Ser Ala Ile Phe Val Pro Thr Ser Glu Asp
His Arg Gln65 70 75 80
Gln Leu Glu Lys Lys Leu Leu Leu Val Asp Val Pro Leu Arg Asn Phe
85 90 95 Gly Gly Phe Lys Ser
Tyr Arg Leu Leu Lys Pro Thr Glu Gly Ser Thr 100
105 110 Tyr Lys Ile Tyr Phe Gly Phe Ala Asn Arg
Thr Ala Tyr Glu Asp Phe 115 120
125 Lys Ala Ser Asp Ile Phe Asn Glu Asn Phe Ser Lys Asp Ala
Leu Ser 130 135 140
Gln Tyr Phe Gly Ala Ser Gly Gln His Ser Ser Tyr Phe Glu Arg Tyr145
150 155 160 Leu Tyr Pro Ile Glu
Asp His 165 201141PRTStaphylococcus sp. 20Met Ile
Asn Arg Asp Asn Lys Lys Ala Ile Thr Lys Lys Gly Met Ile1 5
10 15 Ser Asn Arg Leu Asn Lys Phe
Ser Ile Arg Lys Tyr Thr Val Gly Thr 20 25
30 Ala Ser Ile Leu Val Gly Thr Thr Leu Ile Phe Gly
Leu Gly Asn Gln 35 40 45
Glu Ala Lys Ala Ala Glu Asn Thr Ser Thr Glu Asn Ala Lys Gln Asp
50 55 60 Asp Ala Thr
Thr Ser Asp Asn Lys Glu Val Val Ser Glu Thr Glu Asn65 70
75 80 Asn Ser Thr Thr Glu Asn Asp Ser
Thr Asn Pro Ile Lys Lys Glu Thr 85 90
95 Asn Thr Asp Ser Gln Pro Glu Ala Lys Glu Glu Ser Thr
Thr Ser Ser 100 105 110
Thr Gln Gln Gln Gln Asn Asn Val Thr Ala Thr Thr Glu Thr Lys Pro
115 120 125 Gln Asn Ile Glu
Lys Glu Asn Val Lys Pro Ser Thr Asp Lys Thr Ala 130
135 140 Thr Glu Asp Thr Ser Val Ile Leu
Glu Glu Lys Lys Ala Pro Asn Tyr145 150
155 160 Thr Asn Asn Asp Val Thr Thr Lys Pro Ser Thr Ser
Glu Ile Gln Thr 165 170
175 Lys Pro Thr Thr Pro Gln Glu Ser Thr Asn Ile Glu Asn Ser Gln Pro
180 185 190 Gln Pro Thr
Pro Ser Lys Val Asp Asn Gln Val Thr Asp Ala Thr Asn 195
200 205 Pro Lys Glu Pro Val Asn Val Ser
Lys Glu Glu Leu Lys Asn Asn Pro 210 215
220 Glu Lys Leu Lys Glu Leu Val Arg Asn Asp Asn Asn Thr
Asp Arg Ser225 230 235
240 Thr Lys Pro Val Ala Thr Ala Pro Thr Ser Val Ala Pro Lys Arg Leu
245 250 255 Asn Ala Lys Met
Arg Phe Ala Val Ala Gln Pro Ala Ala Val Ala Ser 260
265 270 Asn Asn Val Asn Asp Leu Ile Thr Val
Thr Lys Gln Thr Ile Lys Val 275 280
285 Gly Asp Gly Lys Asp Asn Val Ala Ala Ala His Asp Gly Lys
Asp Ile 290 295 300
Glu Tyr Asp Thr Glu Phe Thr Ile Asp Asn Lys Val Lys Lys Gly Asp305
310 315 320 Thr Met Thr Ile Asn
Tyr Asp Lys Asn Val Ile Pro Ser Asp Leu Thr 325
330 335 Asp Lys Asn Asp Pro Ile Asp Ile Thr Asp
Pro Ser Gly Glu Val Ile 340 345
350 Ala Lys Gly Thr Phe Asp Lys Ala Thr Lys Gln Ile Thr Tyr Thr
Phe 355 360 365 Thr
Asp Tyr Val Asp Lys Tyr Glu Asp Ile Lys Ala Arg Leu Thr Leu 370
375 380 Tyr Ser Tyr Ile Asp Lys
Gln Ala Val Pro Asn Glu Thr Ser Leu Asn385 390
395 400 Leu Thr Phe Ala Thr Ala Gly Lys Glu Thr Ser
Gln Asn Val Ser Val 405 410
415 Asp Tyr Gln Asp Pro Met Val His Gly Asp Ser Asn Ile Gln Ser Ile
420 425 430 Phe Thr Lys
Leu Asp Glu Asn Lys Gln Thr Ile Glu Gln Gln Ile Tyr 435
440 445 Val Asn Pro Leu Lys Lys Thr Ala
Thr Asn Thr Lys Val Asp Ile Ala 450 455
460 Gly Ser Gln Val Asp Asp Tyr Gly Asn Ile Lys Leu Gly
Asn Gly Ser465 470 475
480 Thr Ile Ile Asp Gln Asn Thr Glu Ile Lys Val Tyr Lys Val Asn Pro
485 490 495 Asn Gln Gln Leu
Pro Gln Ser Asn Arg Ile Tyr Asp Phe Ser Gln Tyr 500
505 510 Glu Asp Val Thr Ser Gln Phe Asp Asn
Lys Lys Ser Phe Ser Asn Asn 515 520
525 Val Ala Thr Leu Asp Phe Gly Asp Ile Asn Ser Ala Tyr Ile
Ile Lys 530 535 540
Val Val Ser Lys Tyr Thr Pro Thr Ser Asp Gly Glu Leu Asp Ile Ala545
550 555 560 Gln Gly Thr Ser Met
Arg Thr Thr Asp Lys Tyr Gly Tyr Tyr Asn Tyr 565
570 575 Ala Gly Tyr Ser Asn Phe Ile Val Thr Ser
Asn Asp Thr Gly Gly Gly 580 585
590 Asp Gly Thr Val Lys Pro Glu Glu Lys Leu Tyr Lys Ile Gly Asp
Tyr 595 600 605 Val
Trp Glu Asp Val Asp Lys Asp Gly Val Gln Gly Thr Asp Ser Lys 610
615 620 Glu Lys Pro Met Ala Asn
Val Leu Val Thr Leu Thr Tyr Pro Asp Gly625 630
635 640 Thr Thr Lys Ser Val Arg Thr Asp Ala Asn Gly
His Tyr Glu Phe Gly 645 650
655 Gly Leu Lys Asp Gly Glu Thr Tyr Thr Val Lys Phe Glu Thr Pro Ala
660 665 670 Gly Tyr Leu
Pro Thr Lys Val Asn Gly Thr Thr Asp Gly Glu Lys Asp 675
680 685 Ser Asn Gly Ser Ser Ile Thr Val
Lys Ile Asn Gly Lys Asp Asp Met 690 695
700 Ser Leu Asp Thr Gly Phe Tyr Lys Glu Pro Lys Tyr Asn
Leu Gly Asp705 710 715
720 Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Ile Gln Asp Ala Asn Glu
725 730 735 Pro Gly Ile Lys
Asp Val Lys Val Thr Leu Lys Asp Ser Thr Gly Lys 740
745 750 Val Ile Gly Thr Thr Thr Thr Asp Ala
Ser Gly Lys Tyr Lys Phe Thr 755 760
765 Asp Leu Asp Asn Gly Asn Tyr Thr Val Glu Phe Glu Thr Pro
Ala Gly 770 775 780
Tyr Thr Pro Thr Val Lys Asn Thr Thr Ala Glu Asp Lys Asp Ser Asn785
790 795 800 Gly Leu Thr Thr Thr
Gly Val Ile Lys Asp Ala Asp Asn Met Thr Leu 805
810 815 Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr
Ser Leu Gly Asp Tyr Val 820 825
830 Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gln Asp Ser Thr Glu Lys
Gly 835 840 845 Ile
Lys Asp Val Lys Val Thr Leu Leu Asn Glu Lys Gly Glu Val Ile 850
855 860 Gly Thr Thr Lys Thr Asp
Glu Asn Gly Lys Tyr Arg Phe Asp Asn Leu865 870
875 880 Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu Lys
Pro Ala Gly Leu Thr 885 890
895 Gln Thr Val Thr Asn Thr Thr Glu Asp Asp Lys Asp Ala Asp Gly Gly
900 905 910 Glu Val Asp
Val Thr Ile Thr Asp His Asp Asp Phe Ile Leu Asp Asn 915
920 925 Gly Tyr Phe Glu Glu Asp Thr Ser
Asp Ser Asp Ser Asp Ser Asp Ser 930 935
940 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser945 950 955
960 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
965 970 975 Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 980
985 990 Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser 995 1000
1005 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser 1010 1015 1020
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser1025
1030 1035 1040Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1045
1050 1055 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser 1060 1065
1070 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys His Thr Pro
Val 1075 1080 1085 Lys
Pro Met Ser Thr Thr Lys Asp His His Asn Lys Ala Lys Ala Leu 1090
1095 1100 Pro Glu Thr Gly Ser Glu
Asn Asn Gly Ser Asn Asn Ala Thr Leu Phe1105 1110
1115 1120Gly Gly Leu Phe Ala Ala Leu Gly Ser Leu Leu
Leu Phe Gly Arg Arg 1125 1130
1135 Lys Lys Gln Asn Lys 1140 211056PRTStaphylococcus
sp. 21Met Ile Asn Lys Lys Asn Asn Leu Leu Thr Lys Lys Lys Pro Ile Ala1
5 10 15 Asn Lys Ser
Asn Lys Tyr Ala Ile Arg Lys Phe Thr Val Gly Thr Ala 20
25 30 Ser Ile Val Ile Gly Ala Thr Leu
Leu Phe Gly Leu Gly His Asn Glu 35 40
45 Ala Lys Ala Glu Glu Asn Ser Val Gln Asp Val Lys Asp
Ser Asn Thr 50 55 60
Asp Asp Glu Leu Ser Asp Ser Asn Asp Gln Ser Ser Asp Glu Glu Lys65
70 75 80 Asn Asp Val Ile Asn
Asn Asn Gln Ser Ile Asn Thr Asp Asp Asn Asn 85
90 95 Gln Ile Ile Lys Lys Glu Glu Thr Asn Asn
Tyr Asp Gly Ile Glu Lys 100 105
110 Arg Ser Glu Asp Arg Thr Glu Ser Thr Thr Asn Val Asp Glu Asn
Glu 115 120 125 Ala
Thr Phe Leu Gln Lys Thr Pro Gln Asp Asn Thr His Leu Thr Glu 130
135 140 Glu Glu Val Lys Glu Ser
Ser Ser Val Glu Ser Ser Asn Ser Ser Ile145 150
155 160 Asp Thr Ala Gln Gln Pro Ser His Thr Thr Ile
Asn Arg Glu Glu Ser 165 170
175 Val Gln Thr Ser Asp Asn Val Glu Asp Ser His Val Ser Asp Phe Ala
180 185 190 Asn Ser Lys
Ile Lys Glu Ser Asn Thr Glu Ser Gly Lys Glu Glu Asn 195
200 205 Thr Ile Glu Gln Pro Asn Lys Val
Lys Glu Asp Ser Thr Thr Ser Gln 210 215
220 Pro Ser Gly Tyr Thr Asn Ile Asp Glu Lys Ile Ser Asn
Gln Asp Glu225 230 235
240 Leu Leu Asn Leu Pro Ile Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu
245 250 255 Ser Thr Thr Ser
Ala Gln Pro Ser Ile Lys Arg Val Thr Val Asn Gln 260
265 270 Leu Ala Ala Glu Gln Gly Ser Asn Val
Asn His Leu Ile Lys Val Thr 275 280
285 Asp Gln Ser Ile Thr Glu Gly Tyr Asp Asp Ser Glu Gly Val
Ile Lys 290 295 300
Ala His Asp Ala Glu Asn Leu Ile Tyr Asp Val Thr Phe Glu Val Asp305
310 315 320 Asp Lys Val Lys Ser
Gly Asp Thr Met Thr Val Asp Ile Asp Lys Asn 325
330 335 Thr Val Pro Ser Asp Leu Thr Asp Ser Phe
Thr Ile Pro Lys Ile Lys 340 345
350 Asp Asn Ser Gly Glu Ile Ile Ala Thr Gly Thr Tyr Asp Asn Lys
Asn 355 360 365 Lys
Gln Ile Thr Tyr Thr Phe Thr Asp Tyr Val Asp Lys Tyr Glu Asn 370
375 380 Ile Lys Ala His Leu Lys
Leu Thr Ser Tyr Ile Asp Lys Ser Lys Val385 390
395 400 Pro Asn Asn Asn Thr Lys Leu Asp Val Glu Tyr
Lys Thr Ala Leu Ser 405 410
415 Ser Val Asn Lys Thr Ile Thr Val Glu Tyr Gln Arg Pro Asn Glu Asn
420 425 430 Arg Thr Ala
Asn Leu Gln Ser Met Phe Thr Asn Ile Asp Thr Lys Asn 435
440 445 His Thr Val Glu Gln Thr Ile Tyr
Ile Asn Pro Leu Arg Tyr Ser Ala 450 455
460 Lys Glu Thr Asn Val Asn Ile Ser Gly Asn Gly Asp Glu
Gly Ser Thr465 470 475
480 Ile Ile Asp Asp Ser Thr Ile Ile Lys Val Tyr Lys Val Gly Asp Asn
485 490 495 Gln Asn Leu Pro
Asp Ser Asn Arg Ile Tyr Asp Tyr Ser Glu Tyr Glu 500
505 510 Asp Val Thr Asn Asp Asp Tyr Ala Gln
Leu Gly Asn Asn Asn Asp Val 515 520
525 Asn Ile Asn Phe Gly Asn Ile Asp Ser Pro Tyr Ile Ile Lys
Val Ile 530 535 540
Ser Lys Tyr Asp Pro Asn Lys Asp Asp Tyr Thr Thr Ile Gln Gln Thr545
550 555 560 Val Thr Met Gln Thr
Thr Ile Asn Glu Tyr Thr Gly Glu Phe Arg Thr 565
570 575 Ala Ser Tyr Asp Asn Thr Ile Ala Phe Ser
Thr Ser Ser Gly Gln Gly 580 585
590 Gln Gly Asp Leu Pro Pro Glu Lys Thr Tyr Lys Ile Gly Asp Tyr
Val 595 600 605 Trp
Glu Asp Val Asp Lys Asp Gly Ile Gln Asn Thr Asn Asp Asn Glu 610
615 620 Lys Pro Leu Ser Asn Val
Leu Val Thr Leu Thr Tyr Pro Asp Gly Thr625 630
635 640 Ser Lys Ser Val Arg Thr Asp Glu Asp Gly Lys
Tyr Gln Phe Asp Gly 645 650
655 Leu Lys Asn Gly Leu Thr Tyr Lys Ile Thr Phe Glu Thr Pro Glu Gly
660 665 670 Tyr Thr Pro
Thr Leu Lys His Ser Gly Thr Asn Pro Ala Leu Asp Ser 675
680 685 Glu Gly Asn Ser Val Trp Val Thr
Ile Asn Gly Gln Asp Asp Met Thr 690 695
700 Ile Asp Ser Gly Phe Tyr Gln Thr Pro Lys Tyr Ser Leu
Gly Asn Tyr705 710 715
720 Val Trp Tyr Asp Thr Asn Lys Asp Gly Ile Gln Gly Asp Asp Glu Lys
725 730 735 Gly Ile Ser Gly
Val Lys Val Thr Leu Lys Asp Glu Asn Gly Asn Ile 740
745 750 Ile Ser Thr Thr Thr Thr Asp Glu Asn
Gly Lys Tyr Gln Phe Asp Asn 755 760
765 Leu Asn Ser Gly Asn Tyr Ile Val His Phe Asp Lys Pro Ser
Gly Met 770 775 780
Thr Gln Thr Thr Thr Asp Ser Gly Asp Asp Asp Glu Gln Asp Ala Asp785
790 795 800 Gly Glu Glu Val His
Val Thr Ile Thr Asp His Asp Asp Phe Ser Ile 805
810 815 Asp Asn Gly Tyr Tyr Asp Asp Glu Ser Asp
Ser Asp Ser Asp Ser Asp 820 825
830 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp 835 840 845 Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 850
855 860 Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp865 870
875 880 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp 885 890
895 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
900 905 910 Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 915
920 925 Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp 930 935
940 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser Asp945 950 955
960 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
965 970 975 Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 980
985 990 Ser Asp Ser Asp Ser Asp Ser Asp Asn
Asp Ser Asp Leu Gly Asn Ser 995 1000
1005 Ser Asp Lys Ser Thr Lys Asp Lys Leu Pro Asp Thr Gly Ala
Asn Glu 1010 1015 1020
Asp Tyr Gly Ser Lys Gly Thr Leu Leu Gly Thr Leu Phe Ala Gly Leu1025
1030 1035 1040Gly Ala Leu Leu Leu
Gly Lys Arg Arg Lys Asn Arg Lys Asn Lys Asn 1045
1050 1055 22486PRTStaphylococcus sp. 22Met Ser Asn
Asn Phe Lys Asp Asp Phe Glu Lys Asn Arg Gln Ser Ile1 5
10 15 Asp Thr Asn Ser His Gln Asp His
Thr Glu Asp Val Glu Lys Asp Gln 20 25
30 Ser Glu Leu Glu His Gln Asp Thr Ile Glu Asn Thr Glu
Gln Gln Phe 35 40 45
Pro Pro Arg Asn Ala Gln Arg Arg Lys Arg Arg Arg Asp Leu Ala Thr 50
55 60 Asn His Asn Lys Gln
Val His Asn Glu Ser Gln Thr Ser Glu Asp Asn65 70
75 80 Val Gln Asn Glu Ala Gly Thr Ile Asp Asp
Arg Gln Val Glu Ser Ser 85 90
95 His Ser Thr Glu Ser Gln Glu Pro Ser His Gln Asp Ser Thr Pro
Gln 100 105 110 His
Glu Glu Glu Tyr Tyr Asn Lys Asn Ala Phe Ala Met Asp Lys Ser 115
120 125 His Pro Glu Pro Ile Glu
Asp Asn Asp Lys His Glu Thr Ile Lys Asp 130 135
140 Ala Glu Asn Asn Thr Glu His Ser Thr Val Ser
Asp Lys Ser Ile Ala145 150 155
160 Glu Gln Ser Gln Gln Pro Lys Pro Tyr Phe Ala Thr Gly Ala Asn Gln
165 170 175 Ala Asn Thr
Ser Lys Asp Lys His Asp Asp Val Thr Val Lys Gln Asp 180
185 190 Lys Asp Glu Ser Lys Asp His His
Ser Gly Lys Lys Gly Ala Ala Ile 195 200
205 Gly Ala Gly Thr Ala Gly Val Ala Gly Ala Ala Gly Ala
Met Gly Val 210 215 220
Ser Lys Ala Lys Lys His Ser Asn Asp Ala Gln Asn Lys Ser Asn Ser225
230 235 240 Asp Lys Ser Asn Asn
Ser Thr Glu Asp Lys Ala Ser Gln Asp Lys Ser 245
250 255 Lys Asp His His Asn Gly Lys Lys Gly Ala
Ala Ile Gly Ala Gly Thr 260 265
270 Ala Gly Leu Ala Gly Gly Ala Ala Ser Lys Ser Ala Ser Ala Ala
Ser 275 280 285 Lys
Pro His Ala Ser Asn Asn Ala Ser Gln Asn His Asp Glu His Asp 290
295 300 Asn His Asp Arg Asp Lys
Glu Arg Lys Lys Gly Gly Met Ala Lys Val305 310
315 320 Leu Leu Pro Leu Ile Ala Ala Val Leu Ile Ile
Gly Ala Leu Ala Ile 325 330
335 Phe Gly Gly Met Ala Leu Asn Asn His Asn Asn Gly Thr Lys Glu Asn
340 345 350 Lys Ile Ala
Asn Thr Asn Lys Asn Asn Ala Asp Glu Ser Lys Asp Lys 355
360 365 Asp Thr Ser Lys Asp Ala Ser Lys
Asp Lys Ser Lys Ser Thr Asp Ser 370 375
380 Asp Lys Ser Lys Glu Asp Gln Asp Lys Ala Thr Lys Asp
Glu Ser Asp385 390 395
400 Asn Asp Gln Asn Asn Ala Asn Gln Ala Asn Asn Gln Ala Gln Asn Asn
405 410 415 Gln Asn Gln Gln
Gln Ala Asn Gln Asn Gln Gln Gln Gln Gln Gln Arg 420
425 430 Gln Gly Gly Gly Gln Arg His Thr Val
Asn Gly Gln Glu Asn Leu Tyr 435 440
445 Arg Ile Ala Ile Gln Tyr Tyr Gly Ser Gly Ser Pro Glu Asn
Val Glu 450 455 460
Lys Ile Arg Arg Ala Asn Gly Leu Ser Gly Asn Asn Ile Arg Asn Gly465
470 475 480 Gln Gln Ile Val Ile
Pro 485 23472PRTStaphylococcus sp. 23Met Ile Glu Leu
Ile Lys Met Glu Gly Met Ile Val Val Ser Asn Asn1 5
10 15 Asn Phe Lys Asp Asp Phe Glu Lys Asn
Arg Gln Ser Ile Asn Pro Asp 20 25
30 Glu Gln Gln Thr Glu Leu Lys Glu Asp Asp Lys Thr Asn Glu
Asn Lys 35 40 45
Lys Glu Ala Asp Ser Gln Asn Ser Leu Ser Asn Asn Ser Asn Gln Gln 50
55 60 Phe Pro Pro Arg Asn
Ala Gln Arg Arg Lys Arg Arg Arg Glu Thr Ala65 70
75 80 Thr Asn Gln Ser Lys Gln Gln Asp Asp Lys
His Gln Lys Asn Ser Asp 85 90
95 Ala Lys Thr Thr Glu Gly Ser Leu Asp Asp Arg Tyr Asp Glu Ala
Gln 100 105 110 Leu
Gln Gln Gln His Asp Lys Ser Gln Gln Gln Asn Lys Thr Glu Lys 115
120 125 Gln Ser Gln Asp Asn Arg
Met Lys Asp Gly Lys Asp Ala Ala Ile Val 130 135
140 Asn Gly Thr Ser Glu Ser Pro Glu His Lys Ser
Lys Ser Thr Gln Asn145 150 155
160 Arg Pro Gly Pro Lys Ala Gln Gln Gln Lys Arg Lys Ser Glu Ser Thr
165 170 175 Gln Ser Lys
Pro Ser Thr Asn Lys Asp Lys Lys Ala Ala Thr Gly Ala 180
185 190 Gly Ile Ala Gly Ala Ala Gly Val
Ala Gly Ala Ala Glu Thr Ser Lys 195 200
205 Arg His His Asn Lys Lys Asp Lys Gln Asp Ser Lys His
Ser Asn His 210 215 220
Glu Asn Asp Glu Lys Ser Val Lys Asn Asp Asp Gln Lys Gln Ser Lys225
230 235 240 Lys Gly Lys Lys Ala
Ala Val Gly Ala Gly Ala Ala Ala Gly Val Gly 245
250 255 Ala Ala Gly Val Ala His His Asn Asn Gln
Asn Lys His His Asn Glu 260 265
270 Glu Lys Asn Ser Asn Gln Asn Asn Gln Tyr Asn Asp Gln Ser Glu
Gly 275 280 285 Lys
Lys Lys Gly Gly Phe Met Lys Ile Leu Leu Pro Leu Ile Ala Ala 290
295 300 Ile Leu Ile Leu Gly Ala
Ile Ala Ile Phe Gly Gly Met Ala Leu Asn305 310
315 320 Asn His Asn Asp Ser Lys Ser Asp Asp Gln Lys
Ile Ala Asn Gln Ser 325 330
335 Lys Lys Asp Ser Asp Lys Lys Asp Gly Ala Gln Ser Glu Asp Asn Lys
340 345 350 Asp Lys Lys
Ser Asp Ser Asn Lys Asp Lys Lys Ser Asp Ser Asp Lys 355
360 365 Asn Ala Asp Asp Asp Ser Asp Asn
Ser Ser Ser Asn Pro Asn Ala Thr 370 375
380 Ser Thr Asn Asn Asn Asp Asn Val Ala Asn Asn Asn Ser
Asn Tyr Thr385 390 395
400 Asn Gln Asn Gln Gln Asp Asn Ala Asn Gln Asn Ser Asn Asn Gln Gln
405 410 415 Ala Thr Gln Gly
Gln Gln Ser His Thr Val Tyr Gly Gln Glu Asn Leu 420
425 430 Tyr Arg Ile Ala Ile Gln Tyr Tyr Gly
Glu Gly Thr Gln Ala Asn Val 435 440
445 Asp Lys Ile Lys Arg Ala Asn Gly Leu Ser Ser Asn Asn Ile
His Asn 450 455 460
Gly Gln Thr Leu Val Ile Pro Gln465 470
24165PRTStaphylococcus sp. 24Met Lys Asn Lys Leu Ile Ala Lys Ser Leu Leu
Thr Ile Ala Ala Ile1 5 10
15 Gly Ile Thr Thr Thr Thr Ile Ala Ser Thr Ala Asp Ala Ser Glu Gly
20 25 30 Tyr Gly Pro
Arg Glu Lys Lys Pro Val Ser Ile Asn His Asn Ile Val 35
40 45 Glu Tyr Asn Asp Gly Thr Phe Lys
Tyr Gln Ser Arg Pro Lys Phe Asn 50 55
60 Ser Thr Pro Lys Tyr Ile Lys Phe Lys His Asp Tyr Asn
Ile Leu Glu65 70 75 80
Phe Asn Asp Gly Thr Phe Glu Tyr Gly Ala Arg Pro Gln Phe Asn Lys
85 90 95 Pro Ala Ala Lys Thr
Asp Ala Thr Ile Lys Lys Glu Gln Lys Leu Ile 100
105 110 Gln Ala Gln Asn Leu Val Arg Glu Phe Glu
Lys Thr His Thr Val Ser 115 120
125 Ala His Arg Lys Ala Gln Lys Ala Val Asn Leu Val Ser Phe
Glu Tyr 130 135 140
Lys Val Lys Lys Met Val Leu Gln Glu Arg Ile Asp Asn Val Leu Lys145
150 155 160 Gln Gly Leu Val Arg
165 25319PRTStaphylococcus sp. 25Met Lys Thr Arg Ile Val
Ser Ser Val Thr Thr Thr Leu Leu Leu Gly1 5
10 15 Ser Ile Leu Met Asn Pro Val Ala Asn Ala Ala
Asp Ser Asp Ile Asn 20 25 30
Ile Lys Thr Gly Thr Thr Asp Ile Gly Ser Asn Thr Thr Val Lys Thr
35 40 45 Gly Asp Leu
Val Thr Tyr Asp Lys Glu Asn Gly Met His Lys Lys Val 50
55 60 Phe Tyr Ser Phe Ile Asp Asp Lys
Asn His Asn Lys Lys Leu Leu Val65 70 75
80 Ile Arg Thr Lys Gly Thr Ile Ala Gly Gln Tyr Arg Val
Tyr Ser Glu 85 90 95
Glu Gly Ala Asn Lys Ser Gly Leu Ala Trp Pro Ser Ala Phe Lys Val
100 105 110 Gln Leu Gln Leu Pro
Asp Asn Glu Val Ala Gln Ile Ser Asp Tyr Tyr 115
120 125 Pro Arg Asn Ser Ile Asp Thr Lys Glu
Tyr Met Ser Thr Leu Thr Tyr 130 135
140 Gly Phe Asn Gly Asn Val Thr Gly Asp Asp Thr Gly Lys
Ile Gly Gly145 150 155
160 Leu Ile Gly Ala Asn Val Ser Ile Gly His Thr Leu Lys Tyr Val Gln
165 170 175 Pro Asp Phe Lys
Thr Ile Leu Glu Ser Pro Thr Asp Lys Lys Val Gly 180
185 190 Trp Lys Val Ile Phe Asn Asn Met Val
Asn Gln Asn Trp Gly Pro Tyr 195 200
205 Asp Arg Asp Ser Trp Asn Pro Val Tyr Gly Asn Gln Leu Phe
Met Lys 210 215 220
Thr Arg Asn Gly Ser Met Lys Ala Ala Glu Asn Phe Leu Asp Pro Asn225
230 235 240 Lys Ala Ser Ser Leu
Leu Ser Ser Gly Phe Ser Pro Asp Phe Ala Thr 245
250 255 Val Ile Thr Met Asp Arg Lys Ala Ser Lys
Gln Gln Thr Asn Ile Asp 260 265
270 Val Ile Tyr Glu Arg Val Arg Asp Asp Tyr Gln Leu His Trp Thr
Ser 275 280 285 Thr
Asn Trp Lys Gly Thr Asn Thr Lys Asp Lys Trp Thr Asp Arg Ser 290
295 300 Ser Glu Arg Tyr Lys Ile
Asp Trp Glu Lys Glu Glu Met Thr Asn305 310
315 26428PRTStaphylococcus sp. 26Met His Met Lys Asn Lys
Tyr Ile Ser Lys Leu Leu Val Gly Ala Ala1 5
10 15 Thr Ile Thr Leu Ala Thr Met Ile Ser Asn Gly
Glu Ala Lys Ala Ser 20 25 30
Glu Asn Thr Gln Gln Thr Ser Thr Lys His Gln Thr Thr Gln Asn Asn
35 40 45 Tyr Val Thr
Asp Gln Gln Lys Ala Phe Tyr Gln Val Leu His Leu Lys 50
55 60 Gly Ile Thr Glu Glu Gln Arg Asn
Gln Tyr Ile Lys Thr Leu Arg Glu65 70 75
80 His Pro Glu Arg Ala Gln Glu Val Phe Ser Glu Ser Leu
Lys Asp Ser 85 90 95
Lys Asn Pro Asp Arg Arg Val Ala Gln Gln Asn Ala Phe Tyr Asn Val
100 105 110 Leu Lys Asn Asp Asn
Leu Thr Glu Gln Glu Lys Asn Asn Tyr Ile Ala 115
120 125 Gln Ile Lys Glu Asn Pro Asp Arg Ser
Gln Gln Val Trp Val Glu Ser 130 135
140 Val Gln Ser Ser Lys Ala Lys Glu Arg Gln Asn Ile Glu
Asn Ala Asp145 150 155
160 Lys Ala Ile Lys Asp Phe Gln Asp Asn Lys Ala Pro His Asp Lys Ser
165 170 175 Ala Ala Tyr Glu
Ala Asn Ser Lys Leu Pro Lys Asp Leu Arg Asp Lys 180
185 190 Asn Asn Arg Phe Val Glu Lys Val Ser
Ile Glu Lys Ala Ile Val Arg 195 200
205 His Asp Glu Arg Val Lys Ser Ala Asn Asp Ala Ile Ser Lys
Leu Asn 210 215 220
Glu Lys Asp Ser Ile Glu Asn Arg Arg Leu Ala Gln Arg Glu Val Asn225
230 235 240 Lys Ala Pro Met Asp
Val Lys Glu His Leu Gln Lys Gln Leu Asp Ala 245
250 255 Leu Val Ala Gln Lys Asp Ala Glu Lys Lys
Val Ala Pro Lys Val Glu 260 265
270 Ala Pro Gln Ile Gln Ser Pro Gln Ile Glu Lys Pro Lys Ala Glu
Ser 275 280 285 Pro
Lys Val Glu Val Pro Gln Ser Lys Leu Leu Gly Tyr Tyr Gln Ser 290
295 300 Leu Lys Asp Ser Phe Asn
Tyr Gly Tyr Lys Tyr Leu Thr Asp Thr Tyr305 310
315 320 Lys Ser Tyr Lys Glu Lys Tyr Asp Thr Ala Lys
Tyr Tyr Tyr Asn Thr 325 330
335 Tyr Tyr Lys Tyr Lys Gly Ala Ile Asp Gln Thr Val Leu Thr Val Leu
340 345 350 Gly Ser Gly
Ser Lys Ser Tyr Ile Gln Pro Leu Lys Val Asp Asp Lys 355
360 365 Asn Gly Tyr Leu Ala Lys Ser Tyr
Ala Gln Val Arg Asn Tyr Val Thr 370 375
380 Glu Ser Ile Asn Thr Gly Lys Val Leu Tyr Thr Phe Tyr
Gln Asn Pro385 390 395
400 Thr Leu Val Lys Thr Ala Ile Lys Ala Gln Glu Thr Ala Ser Ser Ile
405 410 415 Lys Asn Thr Leu
Ser Asn Leu Leu Ser Phe Trp Lys 420 425
27350PRTStaphylococcus sp. 27Met Thr Lys His Tyr Leu Asn Ser Lys Tyr
Gln Ser Glu Gln Arg Ser1 5 10
15 Ser Ala Met Lys Lys Ile Thr Met Gly Thr Ala Ser Ile Ile Leu
Gly 20 25 30 Ser
Leu Val Tyr Ile Gly Ala Asp Ser Gln Gln Val Asn Ala Ala Thr 35
40 45 Glu Ala Thr Asn Ala Thr
Asn Asn Gln Ser Thr Gln Val Ser Gln Ala 50 55
60 Thr Ser Gln Pro Ile Asn Phe Gln Val Gln Lys
Asp Gly Ser Ser Glu65 70 75
80 Lys Ser His Met Asp Asp Tyr Met Gln His Pro Gly Lys Val Ile Lys
85 90 95 Gln Asn Asn
Lys Tyr Tyr Phe Gln Thr Val Leu Asn Asn Ala Ser Phe 100
105 110 Trp Lys Glu Tyr Lys Phe Tyr Asn
Ala Asn Asn Gln Glu Leu Ala Thr 115 120
125 Thr Val Val Asn Asp Asn Lys Lys Ala Asp Thr Arg Thr
Ile Asn Val 130 135 140
Ala Val Glu Pro Gly Tyr Lys Ser Leu Thr Thr Lys Val His Ile Val145
150 155 160 Val Pro Gln Ile Asn
Tyr Asn His Arg Tyr Thr Thr His Leu Glu Phe 165
170 175 Glu Lys Ala Ile Pro Thr Leu Ala Asp Ala
Ala Lys Pro Asn Asn Val 180 185
190 Lys Pro Val Gln Pro Lys Pro Ala Gln Pro Lys Thr Pro Thr Glu
Gln 195 200 205 Thr
Lys Pro Val Gln Pro Lys Val Glu Lys Val Lys Pro Thr Val Thr 210
215 220 Thr Thr Ser Lys Val Glu
Asp Asn His Ser Thr Lys Val Val Ser Thr225 230
235 240 Asp Thr Thr Lys Asp Gln Thr Lys Thr Gln Thr
Ala His Thr Val Lys 245 250
255 Thr Ala Gln Thr Ala Gln Glu Gln Asn Lys Val Gln Thr Pro Val Lys
260 265 270 Asp Val Ala
Thr Ala Lys Ser Glu Ser Asn Asn Gln Ala Val Ser Asp 275
280 285 Asn Lys Ser Gln Gln Thr Asn Lys
Val Thr Lys His Asn Glu Thr Pro 290 295
300 Lys Gln Ala Ser Lys Ala Lys Glu Leu Pro Lys Thr Gly
Leu Thr Ser305 310 315
320 Val Asp Asn Phe Ile Ser Thr Val Ala Phe Ala Thr Leu Ala Leu Leu
325 330 335 Gly Ser Leu Ser
Leu Leu Leu Phe Lys Arg Lys Glu Ser Lys 340
345 350 28645PRTStaphylococcus sp. 28Met Asn Lys Gln Gln
Lys Glu Phe Lys Ser Phe Tyr Ser Ile Arg Lys1 5
10 15 Ser Ser Leu Gly Val Ala Ser Val Ala Ile
Ser Thr Leu Leu Leu Leu 20 25
30 Met Ser Asn Gly Glu Ala Gln Ala Ala Ala Glu Glu Thr Gly Gly
Thr 35 40 45 Asn
Thr Glu Ala Gln Pro Lys Thr Glu Ala Val Ala Ser Pro Thr Thr 50
55 60 Thr Ser Glu Lys Ala Pro
Glu Thr Lys Pro Val Ala Asn Ala Val Ser65 70
75 80 Val Ser Asn Lys Glu Val Glu Ala Pro Thr Ser
Glu Thr Lys Glu Ala 85 90
95 Lys Glu Val Lys Glu Val Lys Ala Pro Lys Glu Thr Lys Ala Val Lys
100 105 110 Pro Ala Ala
Lys Ala Thr Asn Asn Thr Tyr Pro Ile Leu Asn Gln Glu 115
120 125 Leu Arg Glu Ala Ile Lys Asn Pro
Ala Ile Lys Asp Lys Asp His Ser 130 135
140 Ala Pro Asn Ser Arg Pro Ile Asp Phe Glu Met Lys Lys
Glu Asn Gly145 150 155
160 Glu Gln Gln Phe Tyr His Tyr Ala Ser Ser Val Lys Pro Ala Arg Val
165 170 175 Ile Phe Thr Asp
Ser Lys Pro Glu Ile Glu Leu Gly Leu Gln Ser Gly 180
185 190 Gln Phe Trp Arg Lys Phe Glu Val Tyr
Glu Gly Asp Lys Lys Leu Pro 195 200
205 Ile Lys Leu Val Ser Tyr Asp Thr Val Lys Asp Tyr Ala Tyr
Ile Arg 210 215 220
Phe Ser Val Ser Asn Gly Thr Lys Ala Val Lys Ile Val Ser Ser Thr225
230 235 240 His Phe Asn Asn Lys
Glu Glu Lys Tyr Asp Tyr Thr Leu Met Glu Phe 245
250 255 Ala Gln Pro Ile Tyr Asn Ser Ala Asp Lys
Phe Lys Thr Glu Glu Asp 260 265
270 Tyr Lys Ala Glu Lys Leu Leu Ala Pro Tyr Lys Lys Ala Lys Thr
Leu 275 280 285 Glu
Arg Gln Val Tyr Glu Leu Asn Lys Ile Gln Asp Lys Leu Pro Glu 290
295 300 Lys Leu Lys Ala Glu Tyr
Lys Lys Lys Leu Glu Asp Thr Lys Lys Ala305 310
315 320 Leu Asp Glu Gln Val Lys Ser Ala Ile Thr Glu
Phe Gln Asn Val Gln 325 330
335 Pro Thr Asn Glu Lys Met Thr Asp Leu Gln Asp Thr Lys Tyr Val Val
340 345 350 Tyr Glu Ser
Val Glu Asn Asn Glu Ser Met Met Asp Thr Phe Val Lys 355
360 365 His Pro Ile Lys Thr Gly Met Leu
Asn Gly Lys Lys Tyr Met Val Met 370 375
380 Glu Thr Thr Asn Asp Asp Tyr Trp Lys Asp Phe Met Val
Glu Gly Gln385 390 395
400 Arg Val Arg Thr Ile Ser Lys Asp Ala Lys Asn Asn Thr Arg Thr Ile
405 410 415 Ile Phe Pro Tyr
Val Glu Gly Lys Thr Leu Tyr Asp Ala Ile Val Lys 420
425 430 Val His Val Lys Thr Ile Asp Tyr Asp
Gly Gln Tyr His Val Arg Ile 435 440
445 Val Asp Lys Glu Ala Phe Thr Lys Ala Asn Thr Asp Lys Ser
Asn Lys 450 455 460
Lys Glu Gln Gln Asp Asn Ser Ala Lys Lys Glu Ala Thr Pro Ala Thr465
470 475 480 Pro Ser Lys Pro Thr
Pro Ser Pro Val Glu Lys Glu Ser Gln Lys Gln 485
490 495 Asp Ser Gln Lys Asp Asp Asn Lys Gln Leu
Pro Ser Val Glu Lys Glu 500 505
510 Asn Asp Ala Ser Ser Glu Ser Gly Lys Asp Lys Thr Pro Ala Thr
Lys 515 520 525 Pro
Thr Lys Gly Glu Val Glu Ser Ser Ser Thr Thr Pro Thr Lys Val 530
535 540 Val Ser Thr Thr Gln Asn
Val Ala Lys Pro Thr Thr Ala Ser Ser Lys545 550
555 560 Thr Thr Lys Asp Val Val Gln Thr Ser Ala Gly
Ser Ser Glu Ala Lys 565 570
575 Asp Ser Ala Pro Leu Gln Lys Ala Asn Ile Lys Asn Thr Asn Asp Gly
580 585 590 His Thr Gln
Ser Gln Asn Asn Lys Asn Thr Gln Glu Asn Lys Ala Lys 595
600 605 Ser Leu Pro Gln Thr Gly Glu Glu
Ser Asn Lys Asp Met Thr Leu Pro 610 615
620 Leu Met Ala Leu Leu Ala Leu Ser Ser Ile Val Ala Phe
Val Leu Pro625 630 635
640 Arg Lys Arg Lys Asn 645 29953PRTStaphylococcus sp.
29Met Asn Asn Lys Lys Thr Ala Thr Asn Arg Lys Gly Met Ile Pro Asn1
5 10 15 Arg Leu Asn Lys
Phe Ser Ile Arg Lys Tyr Ser Val Gly Thr Ala Ser 20
25 30 Ile Leu Val Gly Thr Thr Leu Ile Phe
Gly Leu Ser Gly His Glu Ala 35 40
45 Lys Ala Ala Glu His Thr Asn Gly Glu Leu Asn Gln Ser Lys
Asn Glu 50 55 60
Thr Thr Ala Pro Ser Glu Asn Lys Thr Thr Glu Lys Val Asp Ser Arg65
70 75 80 Gln Leu Lys Asp Asn
Thr Gln Thr Ala Thr Ala Asp Gln Pro Lys Val 85
90 95 Thr Met Ser Asp Ser Ala Thr Val Lys Glu
Thr Ser Ser Asn Met Gln 100 105
110 Ser Pro Gln Asn Ala Thr Ala Ser Gln Ser Thr Thr Gln Thr Ser
Asn 115 120 125 Val
Thr Thr Asn Asp Lys Ser Ser Thr Thr Tyr Ser Asn Glu Thr Asp 130
135 140 Lys Ser Asn Leu Thr Gln
Ala Lys Asn Val Ser Thr Thr Pro Lys Thr145 150
155 160 Thr Thr Ile Lys Gln Arg Ala Leu Asn Arg Met
Ala Val Asn Thr Val 165 170
175 Ala Ala Pro Gln Gln Gly Thr Asn Val Asn Asp Lys Val His Phe Thr
180 185 190 Asn Ile Asp
Ile Ala Ile Asp Lys Gly His Val Asn Lys Thr Thr Gly 195
200 205 Asn Thr Glu Phe Trp Ala Thr Ser
Ser Asp Val Leu Lys Leu Lys Ala 210 215
220 Asn Tyr Thr Ile Asp Asp Ser Val Lys Glu Gly Asp Thr
Phe Thr Phe225 230 235
240 Lys Tyr Gly Gln Tyr Phe Arg Pro Gly Ser Val Arg Leu Pro Ser Gln
245 250 255 Thr Gln Asn Leu
Tyr Asn Ala Gln Gly Asn Ile Ile Ala Lys Gly Ile 260
265 270 Tyr Asp Ser Lys Thr Asn Thr Thr Thr
Tyr Thr Phe Thr Asn Tyr Val 275 280
285 Asp Gln Tyr Thr Asn Val Ser Gly Ser Phe Glu Gln Val Ala
Phe Ala 290 295 300
Lys Arg Glu Asn Ala Thr Thr Asp Lys Thr Ala Tyr Lys Met Glu Val305
310 315 320 Thr Leu Gly Asn Asp
Thr Tyr Ser Lys Asp Val Ile Val Asp Tyr Gly 325
330 335 Asn Gln Lys Gly Gln Gln Leu Ile Ser Ser
Thr Asn Tyr Ile Asn Asn 340 345
350 Glu Asp Leu Ser Arg Asn Met Thr Val Tyr Val Asn Gln Pro Lys
Lys 355 360 365 Thr
Tyr Thr Lys Glu Thr Phe Val Thr Asn Leu Thr Gly Tyr Lys Phe 370
375 380 Asn Pro Asp Ala Lys Asn
Phe Lys Ile Tyr Glu Val Thr Asp Gln Asn385 390
395 400 Gln Phe Val Asp Ser Phe Thr Pro Asp Thr Ser
Lys Leu Lys Asp Val 405 410
415 Thr Gly Gln Phe Asp Val Ile Tyr Ser Asn Asp Asn Lys Thr Ala Thr
420 425 430 Val Asp Leu
Leu Asn Gly Gln Ser Ser Ser Asp Lys Gln Tyr Ile Ile 435
440 445 Gln Gln Val Ala Tyr Pro Asp Asn
Ser Ser Thr Asp Asn Gly Lys Ile 450 455
460 Asp Tyr Thr Leu Glu Thr Gln Asn Gly Lys Ser Ser Trp
Ser Asn Ser465 470 475
480 Tyr Ser Asn Val Asn Gly Ser Ser Thr Ala Asn Gly Asp Gln Lys Lys
485 490 495 Tyr Asn Leu Gly
Asp Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Lys 500
505 510 Gln Asp Ala Asn Glu Lys Gly Ile Lys
Gly Val Tyr Val Ile Leu Lys 515 520
525 Asp Ser Asn Gly Lys Glu Leu Asp Arg Thr Thr Thr Asp Glu
Asn Gly 530 535 540
Lys Tyr Gln Phe Thr Gly Leu Ser Asn Gly Thr Tyr Ser Val Glu Phe545
550 555 560 Ser Thr Pro Ala Gly
Tyr Thr Pro Thr Thr Ala Asn Ala Gly Thr Asp 565
570 575 Asp Ala Val Asp Ser Asp Gly Leu Thr Thr
Thr Gly Val Ile Lys Asp 580 585
590 Ala Asp Asn Met Thr Leu Asp Ser Gly Phe Tyr Lys Thr Pro Lys
Tyr 595 600 605 Ser
Leu Gly Asp Tyr Val Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gln 610
615 620 Asp Ser Thr Glu Lys Gly
Ile Lys Gly Val Lys Val Thr Leu Gln Asn625 630
635 640 Glu Lys Gly Glu Val Ile Gly Thr Thr Glu Thr
Asp Glu Asn Gly Lys 645 650
655 Tyr Arg Phe Asp Asn Leu Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu
660 665 670 Lys Pro Ala
Gly Leu Thr Gln Thr Gly Thr Asn Thr Thr Glu Asp Asp 675
680 685 Lys Asp Ala Asp Gly Gly Glu Val
Asp Val Thr Ile Thr Asp His Asp 690 695
700 Asp Phe Thr Leu Asp Asn Gly Tyr Tyr Glu Glu Glu Thr
Ser Asp Ser705 710 715
720 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
725 730 735 Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 740
745 750 Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser 755 760
765 Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser 770 775 780
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser785
790 795 800 Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 805
810 815 Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser
Asp Ser Asp Ser Asp Ser 820 825
830 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser 835 840 845 Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 850
855 860 Asp Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser865 870
875 880 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ala Gly Lys 885 890
895 His Thr Pro Thr Lys Pro Met Ser Thr Val Lys Asp Gln His Lys Thr
900 905 910 Ala Lys Ala
Leu Pro Glu Thr Gly Ser Glu Asn Asn Asn Ser Asn Asn 915
920 925 Gly Thr Leu Phe Gly Gly Leu Phe
Ala Ala Leu Gly Ser Leu Leu Leu 930 935
940 Phe Gly Arg Arg Lys Lys Gln Asn Lys945
950 30935PRTStaphylococcus sp. 30Met Asn Met Lys Lys Lys
Glu Lys His Ala Ile Arg Lys Lys Ser Ile1 5
10 15 Gly Val Ala Ser Val Leu Val Gly Thr Leu Ile
Gly Phe Gly Leu Leu 20 25 30
Ser Ser Lys Glu Ala Asp Ala Ser Glu Asn Ser Val Thr Gln Ser Asp
35 40 45 Ser Ala Ser
Asn Glu Ser Lys Ser Asn Asp Ser Ser Ser Val Ser Ala 50
55 60 Ala Pro Lys Thr Asp Asp Thr Asn
Val Ser Asp Thr Lys Thr Ser Ser65 70 75
80 Asn Thr Asn Asn Gly Glu Thr Ser Val Ala Gln Asn Pro
Ala Gln Gln 85 90 95
Glu Thr Thr Gln Ser Ser Ser Thr Asn Ala Thr Thr Glu Glu Thr Pro
100 105 110 Val Thr Gly Glu Ala
Thr Thr Thr Thr Thr Asn Gln Ala Asn Thr Pro 115
120 125 Ala Thr Thr Gln Ser Ser Asn Thr Asn
Ala Glu Glu Leu Val Asn Gln 130 135
140 Thr Ser Asn Glu Thr Thr Ser Asn Asp Thr Asn Thr Val
Ser Ser Val145 150 155
160 Asn Ser Pro Gln Asn Ser Thr Asn Ala Glu Asn Val Ser Thr Thr Gln
165 170 175 Asp Thr Ser Thr
Glu Ala Thr Pro Ser Asn Asn Glu Ser Ala Pro Gln 180
185 190 Asn Thr Asp Ala Ser Asn Lys Asp Val
Val Ser Gln Ala Val Asn Pro 195 200
205 Ser Thr Pro Arg Met Arg Ala Phe Ser Leu Ala Ala Val Ala
Ala Asp 210 215 220
Ala Pro Ala Ala Gly Thr Asp Ile Thr Asn Gln Leu Thr Asp Val Lys225
230 235 240 Val Thr Ile Asp Ser
Gly Thr Thr Val Tyr Pro His Gln Ala Gly Tyr 245
250 255 Val Lys Leu Asn Tyr Gly Phe Ser Val Pro
Asn Ser Ala Val Lys Gly 260 265
270 Asp Thr Phe Lys Ile Thr Val Pro Lys Glu Leu Asn Leu Asn Gly
Val 275 280 285 Thr
Ser Thr Ala Lys Val Pro Pro Ile Met Ala Gly Asp Gln Val Leu 290
295 300 Ala Asn Gly Val Ile Asp
Ser Asp Gly Asn Val Ile Tyr Thr Phe Thr305 310
315 320 Asp Tyr Val Asp Asn Lys Glu Asn Val Thr Ala
Asn Ile Thr Met Pro 325 330
335 Ala Tyr Ile Asp Pro Glu Asn Val Thr Lys Thr Gly Asn Val Thr Leu
340 345 350 Thr Thr Gly
Ile Gly Thr Asn Thr Ala Ser Lys Thr Val Leu Ile Asp 355
360 365 Tyr Glu Lys Tyr Gly Gln Phe His
Asn Leu Ser Ile Lys Gly Thr Ile 370 375
380 Asp Gln Ile Asp Lys Thr Asn Asn Thr Tyr Arg Gln Thr
Ile Tyr Val385 390 395
400 Asn Pro Ser Gly Asp Asn Val Val Leu Pro Ala Leu Thr Gly Asn Leu
405 410 415 Ile Pro Asn Thr
Lys Ser Asn Ala Leu Ile Asp Ala Lys Asn Thr Asp 420
425 430 Ile Lys Val Tyr Arg Val Asp Asn Ala
Asn Asp Leu Ser Glu Ser Tyr 435 440
445 Tyr Val Asn Pro Ser Asp Phe Glu Asp Val Thr Asn Gln Val
Arg Ile 450 455 460
Ser Phe Pro Asn Ala Asn Gln Tyr Lys Val Glu Phe Pro Thr Asp Asp465
470 475 480 Asp Gln Ile Thr Thr
Pro Tyr Ile Val Val Val Asn Gly His Ile Asp 485
490 495 Pro Ala Ser Thr Gly Asp Leu Ala Leu Arg
Ser Thr Phe Tyr Gly Tyr 500 505
510 Asp Ser Asn Phe Ile Trp Arg Ser Met Ser Trp Asp Asn Glu Val
Ala 515 520 525 Phe
Asn Asn Gly Ser Gly Ser Gly Asp Gly Ile Asp Lys Pro Val Val 530
535 540 Pro Glu Gln Pro Asp Glu
Pro Gly Glu Ile Glu Pro Ile Pro Glu Asp545 550
555 560 Ser Asp Ser Asp Pro Gly Ser Asp Ser Gly Ser
Asp Ser Asn Ser Asp 565 570
575 Ser Gly Ser Asp Ser Gly Ser Asp Ser Thr Ser Asp Ser Gly Ser Asp
580 585 590 Ser Ala Ser
Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp 595
600 605 Ser Asp Ser Ala Ser Asp Ser Asp
Ser Ala Ser Asp Ser Asp Ser Ala 610 615
620 Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser
Asp Ser Asp625 630 635
640 Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp
645 650 655 Ser Asp Ser Ala
Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Asp 660
665 670 Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp 675 680
685 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp 690 695 700
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp705
710 715 720 Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 725
730 735 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp 740 745
750 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Ala 755 760 765 Ser
Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp 770
775 780 Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp785 790
795 800 Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser Glu Ser Asp 805 810
815 Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp
820 825 830 Ser Gly Ser
Asp Ser Asp Ser Ser Ser Asp Ser Asp Ser Asp Ser Thr 835
840 845 Ser Asp Thr Gly Ser Asp Asn Asp
Ser Asp Ser Asp Ser Asn Ser Asp 850 855
860 Ser Glu Ser Gly Ser Asn Asn Asn Val Val Pro Pro Asn
Ser Pro Lys865 870 875
880 Asn Gly Thr Asn Ala Ser Asn Lys Asn Glu Ala Lys Asp Ser Lys Glu
885 890 895 Pro Leu Pro Asp
Thr Gly Ser Glu Asp Glu Ala Asn Thr Ser Leu Ile 900
905 910 Trp Gly Leu Leu Ala Ser Leu Gly Ser
Leu Leu Leu Phe Arg Arg Lys 915 920
925 Lys Glu Asn Lys Asp Lys Lys 930 935
311038PRTStaphylococcus sp. 31Met Lys Asn Asn Leu Arg Tyr Gly Ile Arg Lys
His Lys Leu Gly Ala1 5 10
15 Ala Ser Val Phe Leu Gly Thr Met Ile Val Val Gly Met Gly Gln Asp
20 25 30 Lys Glu Ala
Ala Ala Ser Glu Gln Lys Thr Thr Thr Val Glu Glu Asn 35
40 45 Gly Asn Ser Ala Thr Asp Asn Lys
Thr Ser Glu Thr Gln Thr Thr Ala 50 55
60 Thr Asn Val Asn His Ile Glu Glu Thr Gln Ser Tyr Asn
Ala Thr Val65 70 75 80
Thr Glu Gln Pro Ser Asn Ala Thr Gln Val Thr Thr Glu Glu Ala Pro
85 90 95 Lys Ala Val Gln Ala
Pro Gln Thr Ala Gln Pro Ala Asn Val Glu Thr 100
105 110 Val Lys Glu Glu Glu Lys Pro Gln Val Lys
Glu Thr Thr Gln Pro Gln 115 120
125 Asp Asn Ser Gly Asn Gln Arg Gln Val Asp Leu Thr Pro Lys
Lys Val 130 135 140
Thr Gln Asn Gln Gly Thr Glu Thr Gln Val Glu Val Ala Gln Pro Arg145
150 155 160 Thr Ala Ser Glu Ser
Lys Pro Arg Val Thr Arg Ser Ala Asp Val Ala 165
170 175 Glu Ala Lys Glu Ala Ser Asp Val Ser Glu
Val Lys Gly Thr Asp Val 180 185
190 Thr Ser Lys Val Thr Val Glu Ser Gly Ser Ile Glu Ala Pro Gln
Gly 195 200 205 Asn
Lys Val Glu Pro His Ala Gly Gln Arg Val Val Leu Lys Tyr Lys 210
215 220 Leu Lys Phe Ala Asp Gly
Leu Lys Arg Gly Asp Tyr Phe Asp Phe Thr225 230
235 240 Leu Ser Asn Asn Val Asn Thr Tyr Gly Val Ser
Thr Ala Arg Lys Val 245 250
255 Pro Glu Ile Lys Asn Gly Ser Val Val Met Ala Thr Gly Glu Ile Leu
260 265 270 Gly Asn Gly
Asn Ile Arg Tyr Thr Phe Thr Asn Glu Ile Glu His Lys 275
280 285 Val Glu Val Thr Ala Asn Leu Glu
Ile Asn Leu Phe Ile Asp Pro Lys 290 295
300 Thr Val Gln Ser Asn Gly Glu Gln Lys Ile Thr Ser Lys
Leu Asn Gly305 310 315
320 Glu Glu Thr Glu Lys Thr Ile Pro Val Val Tyr Asn Pro Gly Val Ser
325 330 335 Asn Ser Tyr Thr
Asn Val Asn Gly Ser Ile Glu Thr Phe Asn Lys Glu 340
345 350 Ser Asn Lys Phe Thr His Ile Ala Tyr
Ile Lys Pro Met Asn Gly Asn 355 360
365 Gln Ser Asn Thr Val Ser Val Thr Gly Thr Leu Thr Glu Gly
Ser Asn 370 375 380
Leu Ala Gly Gly Gln Pro Thr Val Lys Val Tyr Glu Tyr Leu Gly Lys385
390 395 400 Lys Asp Glu Leu Pro
Gln Ser Val Tyr Ala Asn Thr Ser Asp Thr Asn 405
410 415 Lys Phe Lys Asp Val Thr Lys Glu Met Asn
Gly Lys Leu Ser Val Gln 420 425
430 Asp Asn Gly Ser Tyr Ser Leu Asn Leu Asp Lys Leu Asp Lys Thr
Tyr 435 440 445 Val
Ile His Tyr Thr Gly Glu Tyr Leu Gln Gly Ser Asp Gln Val Asn 450
455 460 Phe Arg Thr Glu Leu Tyr
Gly Tyr Pro Glu Arg Ala Tyr Lys Ser Tyr465 470
475 480 Tyr Val Tyr Gly Gly Tyr Arg Leu Thr Trp Asp
Asn Gly Leu Val Leu 485 490
495 Tyr Ser Asn Lys Ala Asp Gly Asn Gly Lys Asn Gly Gln Ile Ile Gln
500 505 510 Asp Asn Asp
Phe Glu Tyr Lys Glu Asp Thr Ala Lys Gly Thr Met Ser 515
520 525 Gly Gln Tyr Asp Ala Lys Gln Ile
Ile Glu Thr Glu Glu Asn Gln Asp 530 535
540 Asn Thr Pro Leu Asp Ile Asp Tyr His Thr Ala Ile Asp
Gly Glu Gly545 550 555
560 Gly Tyr Val Asp Gly Tyr Ile Glu Thr Ile Glu Glu Thr Asp Ser Ser
565 570 575 Ala Ile Asp Ile
Asp Tyr His Thr Ala Val Asp Ser Glu Val Gly His 580
585 590 Val Gly Gly Tyr Thr Glu Ser Ser Glu
Glu Ser Asn Pro Ile Asp Phe 595 600
605 Glu Glu Ser Thr His Glu Asn Ser Lys His His Ala Asp Val
Val Glu 610 615 620
Tyr Glu Glu Asp Thr Asn Pro Gly Gly Gly Gln Val Thr Thr Glu Ser625
630 635 640 Asn Leu Val Glu Phe
Asp Glu Glu Ser Thr Lys Gly Ile Val Thr Gly 645
650 655 Ala Val Ser Asp His Thr Thr Ile Glu Asp
Thr Lys Glu Tyr Thr Thr 660 665
670 Glu Ser Asn Leu Ile Glu Leu Val Asp Glu Leu Pro Glu Glu His
Gly 675 680 685 Gln
Ala Gln Gly Pro Ile Glu Glu Ile Thr Glu Asn Asn His His Ile 690
695 700 Ser His Ser Gly Leu Gly
Thr Glu Asn Gly His Gly Asn Tyr Gly Val705 710
715 720 Ile Glu Glu Ile Glu Glu Asn Ser His Val Asp
Ile Lys Ser Glu Leu 725 730
735 Gly Tyr Glu Gly Gly Gln Asn Ser Gly Asn Gln Ser Phe Glu Glu Asp
740 745 750 Thr Glu Glu
Asp Lys Pro Lys Tyr Glu Gln Gly Gly Asn Ile Val Asp 755
760 765 Ile Asp Phe Asp Ser Val Pro Gln
Ile His Gly Gln Asn Lys Gly Asp 770 775
780 Gln Ser Phe Glu Glu Asp Thr Glu Lys Asp Lys Pro Lys
Tyr Glu His785 790 795
800 Gly Gly Asn Ile Ile Asp Ile Asp Phe Asp Ser Val Pro Gln Ile His
805 810 815 Gly Phe Asn Lys
His Asn Glu Ile Ile Glu Glu Asp Thr Asn Lys Asp 820
825 830 Lys Pro Asn Tyr Gln Phe Gly Gly His
Asn Ser Val Asp Phe Glu Glu 835 840
845 Asp Thr Leu Pro Lys Val Ser Gly Gln Asn Glu Gly Gln Gln
Thr Ile 850 855 860
Glu Glu Asp Thr Thr Pro Pro Thr Pro Pro Thr Pro Glu Val Pro Ser865
870 875 880 Glu Pro Glu Thr Pro
Met Pro Pro Thr Pro Glu Val Pro Ser Glu Pro 885
890 895 Glu Thr Pro Thr Pro Pro Thr Pro Glu Val
Pro Ser Glu Pro Glu Thr 900 905
910 Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr Pro
Thr 915 920 925 Pro
Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr Pro Thr Pro Pro 930
935 940 Thr Pro Glu Val Pro Ala
Glu Pro Gly Lys Pro Val Pro Pro Ala Lys945 950
955 960 Glu Glu Pro Lys Lys Pro Ser Lys Pro Val Glu
Gln Gly Lys Val Val 965 970
975 Thr Pro Val Ile Glu Ile Asn Glu Lys Val Lys Ala Val Ala Pro Thr
980 985 990 Lys Lys Ala
Gln Ser Lys Lys Ser Glu Leu Pro Glu Thr Gly Gly Glu 995
1000 1005 Glu Ser Thr Asn Lys Gly Met Leu
Phe Gly Gly Leu Phe Ser Ile Leu 1010 1015
1020 Gly Leu Ala Leu Leu Arg Arg Asn Lys Lys Asn Asn Lys
Ala1025 1030 1035
32877PRTStaphylococcus sp. 32Met Lys Lys Arg Ile Asp Tyr Leu Ser Asn Lys
Gln Asn Lys Tyr Ser1 5 10
15 Ile Arg Arg Phe Thr Val Gly Thr Thr Ser Val Ile Val Gly Ala Thr
20 25 30 Ile Leu Phe
Gly Ile Gly Asn His Gln Ala Gln Ala Ser Glu Gln Ser 35
40 45 Asn Asp Thr Thr Gln Ser Ser Lys
Asn Asn Ala Ser Ala Asp Ser Glu 50 55
60 Lys Asn Asn Met Ile Glu Thr Pro Gln Leu Asn Thr Thr
Ala Asn Asp65 70 75 80
Thr Ser Asp Ile Ser Ala Asn Thr Asn Ser Ala Asn Val Asp Ser Thr
85 90 95 Thr Lys Pro Met Ser
Thr Gln Thr Ser Asn Thr Thr Thr Thr Glu Pro 100
105 110 Ala Ser Thr Asn Glu Thr Pro Gln Pro Thr
Ala Ile Lys Asn Gln Ala 115 120
125 Thr Ala Ala Lys Met Gln Asp Gln Thr Val Pro Gln Glu Ala
Asn Ser 130 135 140
Gln Val Asp Asn Lys Thr Thr Asn Asp Ala Asn Ser Ile Ala Thr Asn145
150 155 160 Ser Glu Leu Lys Asn
Ser Gln Thr Leu Asp Leu Pro Gln Ser Ser Pro 165
170 175 Gln Thr Ile Ser Asn Ala Gln Gly Thr Ser
Lys Pro Ser Val Arg Thr 180 185
190 Arg Ala Val Arg Ser Leu Ala Val Ala Glu Pro Val Val Asn Ala
Ala 195 200 205 Asp
Ala Lys Gly Thr Asn Val Asn Asp Lys Val Thr Ala Ser Asn Phe 210
215 220 Lys Leu Glu Lys Thr Thr
Phe Asp Pro Asn Gln Ser Gly Asn Thr Phe225 230
235 240 Met Ala Ala Asn Phe Thr Val Thr Asp Lys Val
Lys Ser Gly Asp Tyr 245 250
255 Phe Thr Ala Lys Leu Pro Asp Ser Leu Thr Gly Asn Gly Asp Val Asp
260 265 270 Tyr Ser Asn
Ser Asn Asn Thr Met Pro Ile Ala Asp Ile Lys Ser Thr 275
280 285 Asn Gly Asp Val Val Ala Lys Ala
Thr Tyr Asp Ile Leu Thr Lys Thr 290 295
300 Tyr Thr Phe Val Phe Thr Asp Tyr Val Asn Asn Lys Glu
Asn Ile Asn305 310 315
320 Gly Gln Phe Ser Leu Pro Leu Phe Thr Asp Arg Ala Lys Ala Pro Lys
325 330 335 Ser Gly Thr Tyr
Asp Ala Asn Ile Asn Ile Ala Asp Glu Met Phe Asn 340
345 350 Asn Lys Ile Thr Tyr Asn Tyr Ser Ser
Pro Ile Ala Gly Ile Asp Lys 355 360
365 Pro Asn Gly Ala Asn Ile Ser Ser Gln Ile Ile Gly Val Asp
Thr Ala 370 375 380
Ser Gly Gln Asn Thr Tyr Lys Gln Thr Val Phe Val Asn Pro Lys Gln385
390 395 400 Arg Val Leu Gly Asn
Thr Trp Val Tyr Ile Lys Gly Tyr Gln Asp Lys 405
410 415 Ile Glu Glu Ser Ser Gly Lys Val Ser Ala
Thr Asp Thr Lys Leu Arg 420 425
430 Ile Phe Glu Val Asn Asp Thr Ser Lys Leu Ser Asp Ser Tyr Tyr
Ala 435 440 445 Asp
Pro Asn Asp Ser Asn Leu Lys Glu Val Thr Asp Gln Phe Lys Asn 450
455 460 Arg Ile Tyr Tyr Glu His
Pro Asn Val Ala Ser Ile Lys Phe Gly Asp465 470
475 480 Ile Thr Lys Thr Tyr Val Val Leu Val Glu Gly
His Tyr Asp Asn Thr 485 490
495 Gly Lys Asn Leu Lys Thr Gln Val Ile Gln Glu Asn Val Asp Pro Val
500 505 510 Thr Asn Arg
Asp Tyr Ser Ile Phe Gly Trp Asn Asn Glu Asn Val Val 515
520 525 Arg Tyr Gly Gly Gly Ser Ala Asp
Gly Asp Ser Ala Val Asn Pro Lys 530 535
540 Asp Pro Thr Pro Gly Pro Pro Val Asp Pro Glu Pro Ser
Pro Asp Pro545 550 555
560 Glu Pro Glu Pro Thr Pro Asp Pro Glu Pro Ser Pro Asp Pro Glu Pro
565 570 575 Glu Pro Ser Pro
Asp Pro Asp Pro Asp Ser Asp Ser Asp Ser Asp Ser 580
585 590 Gly Ser Asp Ser Asp Ser Gly Ser Asp
Ser Asp Ser Glu Ser Asp Ser 595 600
605 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Glu Ser 610 615 620
Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser625
630 635 640 Asp Ser Asp Ser Asp
Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser 645
650 655 Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser
Asp Ser Asp Ser Glu Ser 660 665
670 Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser 675 680 685 Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 690
695 700 Asp Ser Asp Ser Asp Ser
Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser705 710
715 720 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser 725 730
735 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
740 745 750 Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 755
760 765 Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser 770 775
780 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser785 790 795
800 Asp Ser Asp Ser Arg Val Thr Pro Pro Asn Asn Glu Gln Lys Ala Pro
805 810 815 Ser Asn Pro Lys
Gly Glu Val Asn His Ser Asn Lys Val Ser Lys Gln 820
825 830 His Lys Thr Asp Ala Leu Pro Glu Thr
Gly Asp Lys Ser Glu Asn Thr 835 840
845 Asn Ala Thr Leu Phe Gly Ala Met Met Ala Leu Leu Gly Ser
Leu Leu 850 855 860
Leu Phe Arg Lys Arg Lys Gln Asp His Lys Glu Lys Ala865
870 875 33658PRTStaphylococcus sp. 33Met Lys Lys
Gln Ile Ile Ser Leu Gly Ala Leu Ala Val Ala Ser Ser1 5
10 15 Leu Phe Thr Trp Asp Asn Lys Ala
Asp Ala Ile Val Thr Lys Asp Tyr 20 25
30 Ser Lys Glu Ser Arg Val Asn Glu Lys Ser Lys Lys Gly
Ala Thr Val 35 40 45
Ser Asp Tyr Tyr Tyr Trp Lys Ile Ile Asp Ser Leu Glu Ala Gln Phe 50
55 60 Thr Gly Ala Ile Asp
Leu Leu Glu Asp Tyr Lys Tyr Gly Asp Pro Ile65 70
75 80 Tyr Lys Glu Ala Lys Asp Arg Leu Met Thr
Arg Val Leu Gly Glu Asp 85 90
95 Gln Tyr Leu Leu Lys Lys Lys Ile Asp Glu Tyr Glu Leu Tyr Lys
Lys 100 105 110 Trp
Tyr Lys Ser Ser Asn Lys Asn Thr Asn Met Leu Thr Phe His Lys 115
120 125 Tyr Asn Leu Tyr Asn Leu
Thr Met Asn Glu Tyr Asn Asp Ile Phe Asn 130 135
140 Ser Leu Lys Asp Ala Val Tyr Gln Phe Asn Lys
Glu Val Lys Glu Ile145 150 155
160 Glu His Lys Asn Val Asp Leu Lys Gln Phe Asp Lys Asp Gly Glu Asp
165 170 175 Lys Ala Thr
Lys Glu Val Tyr Asp Leu Val Ser Glu Ile Asp Thr Leu 180
185 190 Val Val Thr Tyr Tyr Ala Asp Lys
Asp Tyr Gly Glu His Ala Lys Glu 195 200
205 Leu Arg Ala Lys Leu Asp Leu Ile Leu Gly Asp Thr Asp
Asn Pro His 210 215 220
Lys Ile Thr Asn Glu Arg Ile Lys Lys Glu Met Ile Asp Asp Leu Asn225
230 235 240 Ser Ile Ile Asp Asp
Phe Phe Met Glu Thr Lys Gln Asn Arg Pro Asn 245
250 255 Ser Ile Thr Lys Tyr Asp Pro Thr Lys His
Asn Phe Lys Glu Lys Ser 260 265
270 Glu Asn Lys Pro Asn Phe Asp Lys Leu Val Glu Glu Thr Lys Lys
Ala 275 280 285 Val
Lys Glu Ala Asp Glu Ser Trp Lys Asn Lys Thr Val Lys Lys Tyr 290
295 300 Glu Glu Thr Val Thr Lys
Ser Pro Val Val Lys Glu Glu Lys Lys Val305 310
315 320 Glu Glu Pro Gln Leu Pro Lys Val Gly Asn Gln
Gln Glu Val Lys Thr 325 330
335 Thr Ala Gly Lys Ala Glu Glu Thr Thr Gln Pro Val Ala Gln Pro Leu
340 345 350 Val Lys Ile
Pro Gln Glu Thr Ile Tyr Gly Glu Thr Val Lys Gly Pro 355
360 365 Glu Tyr Pro Thr Met Glu Asn Lys
Thr Leu Gln Gly Glu Ile Val Gln 370 375
380 Gly Pro Asp Phe Leu Thr Met Glu Gln Asn Arg Pro Ser
Leu Ser Asp385 390 395
400 Asn Tyr Thr Gln Pro Thr Thr Pro Asn Pro Ile Leu Glu Gly Leu Glu
405 410 415 Gly Ser Ser Ser
Lys Leu Glu Ile Lys Pro Gln Gly Thr Glu Ser Thr 420
425 430 Leu Lys Gly Ile Gln Gly Glu Ser Ser
Asp Ile Glu Val Lys Pro Gln 435 440
445 Ala Thr Glu Thr Thr Glu Ala Ser Gln Tyr Gly Pro Arg Pro
Gln Phe 450 455 460
Asn Lys Thr Pro Lys Tyr Val Lys Tyr Arg Asp Ala Gly Thr Gly Ile465
470 475 480 Arg Glu Tyr Asn Asp
Gly Thr Phe Gly Tyr Glu Ala Arg Pro Arg Phe 485
490 495 Asn Lys Pro Ser Glu Thr Asn Ala Tyr Asn
Val Thr Thr Asn Gln Asp 500 505
510 Gly Thr Val Ser Tyr Gly Ala Arg Pro Thr Gln Asn Lys Pro Ser
Glu 515 520 525 Thr
Asn Ala Tyr Asn Val Thr Thr His Ala Asn Gly Gln Val Ser Tyr 530
535 540 Gly Ala Arg Pro Thr Gln
Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn545 550
555 560 Val Thr Thr His Ala Asn Gly Gln Val Ser Tyr
Gly Ala Arg Pro Thr 565 570
575 Gln Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn Val Thr Thr His Ala
580 585 590 Asn Gly Gln
Val Ser Tyr Gly Ala Arg Pro Thr Tyr Lys Lys Pro Ser 595
600 605 Glu Thr Asn Ala Tyr Asn Val Thr
Thr His Ala Asn Gly Gln Val Ser 610 615
620 Tyr Gly Ala Arg Pro Thr Gln Lys Lys Pro Ser Glu Thr
Asn Ala Tyr625 630 635
640 Asn Val Thr Thr His Ala Asp Gly Thr Ala Thr Tyr Gly Pro Arg Val
645 650 655 Thr
Lys341602DNAStaphylococcus sp. 34atgttacaag taactgatgt gagtttacgt
tttggagatc gtaaactatt tgaagatgta 60aatattaaat ttacagaagg taattgttat
ggattaattg gtgcgaatgg tgcaggtaaa 120tcaacattct taaaaatatt atctggtgaa
ttagattctc aaacaggaca tgtttcatta 180ggtaaaaatg aacgtctagc tgttttaaaa
caggaccact atgcttatga agatgaacgc 240gtgcttgatg ttgtaattaa aggtcacgaa
cgtctttatg aggttatgaa agaaaaagat 300gaaatctata tgaagccaga tttcagtgat
gaagatggta tccgtgctgc tgaacttgaa 360ggtgaatttg cagaaatgaa tggttggaat
gctgaagctg atgctgctaa ccttttatct 420ggtttaggta tcgatccaac tttacacgat
aaaaaaatgg ctgaattaga aaacaaccaa 480aaaattaaag tattattagc gcaaagttta
ttcggtgaac cagacgtact attactggat 540gagcctacta acggtctcga tattccagca
atcagttggt tagaagattt cttaattaac 600tttgataata ctgttatcgt agtatcgcat
gaccgtcatt tcttaaataa tgtatgtact 660catatcgctg atttagactt cggtaaaatt
aaagtttatg ttggtaacta tgatttttgg 720tatcaatcta gtcagttagc tcaaaagatg
gctcaagaac aaaacaagaa aaaagaagaa 780aaaatgaaag agttacagga ctttattgca
cgtttctcag ctaacgcttc taaatctaaa 840caagcaacaa gtcgtaaaaa acaacttgag
aaaattgaat tagatgatat tcaaccatca 900tcaagaagat atcctttcgt taaattcacg
cctgagcgtg agattggtaa cgacttatta 960atcgttcaaa atctttctaa aacaattgac
ggcgaaaaag tattagataa tgtatcattc 1020acaatgaatc caaatgataa agcgatttta
attggagata gtgaaattgc aaaaacaaca 1080ttacttaaaa tattagctgg cgaaatggaa
ccagacgaag gttcatttaa atggggtgtt 1140actacatcat taagttactt ccctaaagat
aactcagagt tctttgaggg tgtaaatatg 1200aatctcgttg attggttaag acaatatgct
cctgaagatg aacaaacaga aacattttta 1260cgtggtttct taggtcgtat gttatttagt
ggtgaagaag ttaagaaaaa agctagtgtg 1320ctttcaggtg gagaaaaagt acgttgtatg
ctaagtaaaa tgatgttatc aagtgcgaat 1380gtacttttac ttgacgaacc tactaaccac
ttagacttag aaagtattac tgctgtcaat 1440gatggtctta aatcatttaa aggttctatc
atctttactt cttatgactt cgaatttatc 1500aacacgattg caaaccgtgt tatcgattta
aataaacaag gcggcgtttc aaaagaaatt 1560ccatatgaag aatacttgca agaaatcggc
gttttaaaat aa 1602351608DNAStaphylococcus sp.
35atgttacaag taactgatgt aagtttacgt tttggtgatc gtaaactatt tgaagatgta
60aatataaaat ttacagaggg taattgttat ggattaattg gtgcaaatgg tgctgggaaa
120tctacattct tgaagatttt atcaggcgaa attgattcac agactggtca tgtatctcta
180ggtaaagatg agcgtttggc tgtgttaaaa caagatcatt ttgcttatga agatgaacgt
240gttttagatg ttgtgattaa aggacatgaa cgtttgtatc aagtgatgaa agagaaagat
300gaaatttata tgaaacctga tttcagcgat gaggacggta ttcgcgctgc agaacttgaa
360ggagaatttg cagaaatgaa cggttggaat gctgaagctg atgctgctaa cttattatca
420ggattaggca tagaacctga cttacatgat aaaaatatgt ctgaacttga aaataatcaa
480aaagttaagg tattgttagc tcaaagttta tttggtgatc ctgacgttct tttactagat
540gagcctacca atggtttaga tataccagca ataagttggt tagaagactt tttaattaat
600tttgaaaata ctgtcattgt cgtttcgcat gaccgtcact tcttaaataa tgtttgtact
660catattgctg atttagactt tggcaaaatt aaactttatg ttggtaacta tgatttttgg
720tatcaatcaa gtcaattagc acaaaaaatg gcacaagaac aaaataagaa aaaagaagaa
780aaaatgaaag agttacagga tttcatcgca cgcttctcag caaatgcttc taaatctaaa
840caggcaacaa gtcgtaagaa acaattagaa aaaattgaat tagatgatat ccagccatca
900tctcgtagat acccttacgt gaaatttact cctgaacgtg aaattggaaa tgatttactt
960acagtagaaa atctttctaa aacaattgac ggcgaaaaag tactagacaa tgtttcattc
1020actatgaatc ctaatgataa agctatttta gttggtgata gcgaaattgc taaaacaaca
1080ttgttaaaaa ttttagctgg agaaatggaa ccagatgaag gtacatttaa atggggtgta
1140acgacatctt taagttactt ccctaaagat aactctgagt tctttgatgg tgtcgatatg
1200aatttagttg aatggttacg tcaatacgct ccagaagatg aacaaactga aacattttta
1260cgtggtttct taggtcgcat gttatttagt ggtgaggaag ttaagaaaaa agcaagcgtg
1320ctttcaggtg gagaaaaagt acgttgcatg ttaagtaaaa tgatgttatc aagtgctaac
1380gtacttttac ttgatgagcc aacaaaccat ttagatttgg aaagtatcac tgctgtaaat
1440gacggattaa aatcatttaa aggttctatc atcttcactt cttatgattt tgaatttatt
1500aatacaatcg caaatcgagt gattgacttg aatcaagctg gtgccctttc taaagaagta
1560ccttatgagg aatacttaca agaaattggt gtattacaaa ataattaa
1608361305DNAStaphylococcus sp. 36atgccaatta ttacagatgt ttacgctcgc
gaagtcttag actctcgtgg taacccaact 60gttgaagtag aagtattaac tgaaagtggc
gcatttggtc gtgcattagt accatcaggt 120gcttcaactg gtgaacacga agctgttgaa
ttacgtgatg gagacaaatc acgttattta 180ggtaaaggtg ttactaaagc agttgaaaac
gttaatgaaa tcatcgcacc agaaattatt 240gaaggtgaat tttcagtatt agatcaagta
tctattgata aaatgatgat cgcattagac 300ggtactccaa acaaaggtaa attaggtgca
aatgctattt taggtgtatc tatcgcagta 360gcacgtgcag cagctgactt attaggtcaa
ccactttaca aatatttagg tggatttaat 420ggtaagcagt taccagtacc aatgatgaac
atcgttaatg gtggttctca ctcagatgct 480ccaattgcat tccaagaatt catgatttta
cctgtaggtg ctacaacgtt caaagaatca 540ttacgttggg gtactgaaat tttccacaac
ttaaaatcaa ttttaagcaa acgtggttta 600gaaactgcag taggtgacga aggtggtttc
gctcctaaat ttgaaggtac tgaagatgct 660gttgaaacaa ttatccaagc aatcgaagca
gctggttaca aaccaggtga agaagtattc 720ttaggatttg actgtgcatc atcagaattc
tatgaaaatg gtgtatatga ctacagtaag 780ttcgaaggcg aacacggtgc aaaacgtaca
gctgcagaac aagttgacta cttagaacaa 840ttagtagaca aatatcctat cattacaatt
gaagacggta tggacgaaaa cgactgggat 900ggttggaaac aacttacaga acgtatcggt
gaccgtgtac aattagtagg tgacgattta 960ttcgtaacaa acactgaaat tttagcaaaa
ggtattgaaa acggaattgg taactcaatc 1020ttaattaaag ttaaccaaat cggtacatta
actgaaacat ttgatgcaat cgaaatggct 1080caaaaagctg gttacacagc agtagtttct
caccgttcag gtgaaacaga agatacaaca 1140attgctgata ttgctgttgc tacaaacgct
ggtcaaatta aaactggttc attatcacgt 1200actgaccgta ttgctaaata caatcaatta
ttacgtatcg aagatgaatt atttgaaact 1260gctaaatatg acggtatcaa atcattctat
aacttagata aataa 1305371305DNAStaphylococcus sp.
37atgccaatta ttacagatgt ttacgctcgc gaagtcttag actcacgtgg taacccaaca
60gttgaagttg aagtattaac tgaaagcggt gctttcggac gtgcattagt accttctggt
120gcttctactg gtgaacatga agcagttgaa ttacgtgatg gagataaatc acgttattta
180ggtaaaggtg tgactaaagc ggtagaaaat gttaacgaaa tgatcgcacc agaaatcgtt
240gaaggtgaat tttcagtttt agatcaagta tctattgata aaatgatgat tcaattagac
300ggtacacaca acaaaggtaa attaggtgca aatgccattt taggtgtttc tattgccgta
360gctcgtgcag ctgctgactt attaggtcaa ccattatata aatatttagg tggatttaat
420ggtaaacaat tgccagtacc tatgatgaat attgttaatg gtggttctca ctcagatgca
480ccaattgctt tccaagagtt catgatttta cctgtaggtg ctgagtcatt caaagaatca
540ttacgttggg gtgcagaaat cttccataac cttaaatcaa tcttaagtga acgtggttta
600gaaactgcag taggtgatga aggtggtttc gctcctagat ttgaaggcac tgaagacgct
660gtagaaacta ttattaaagc tatcgaaaaa gcaggataca aaccaggtga agatgtattc
720ttaggatttg actgtgcttc ttctgaattc tatgaaaatg gtgtttatga ttacactaaa
780ttcgaaggtg aacacggtgc taaacgtagt gcagcagagc aagttgacta cttagaagaa
840ttaattggta aatatccaat catcactatt gaagatggta tggatgaaaa cgattgggaa
900ggttggaaac aattaactga tcgtatcggt gataaagttc aattagttgg tgatgattta
960ttcgtaacta acactgaaat tttatctaaa ggtatcgaac aaggtattgg taactcaatc
1020ttaatcaaag taaaccaaat cggtacatta actgaaacat tcgatgctat tgaaatggct
1080caaaaagctg gatatactgc ggttgtatct caccgttctg gtgaaactga agatactaca
1140attgctgata tcgcagttgc tacaaatgca ggccaaatta aaacaggttc attatctaga
1200actgaccgta ttgctaaata caatcaatta ttacgtattg aagatgaatt atacgaaaca
1260gctaaatttg aaggaattaa atctttctac aatttagata aataa
130538768DNAStaphylococcus sp. 38atgaaaaaaa tcgttacagc tacaatcgct
acagcaggac ttgccactat cgcatttgca 60ggacatgatg cacaagccgc agaacaaaat
aacaatggat ataattctaa tgacgctcaa 120tcatacagct atacgtatac aattgatgca
caaggtaatt atcattacac ttggacagga 180aattggaatc caagtcaatt aacgcaaaac
aacacatact actacaacaa ctacaatact 240tatagttata acaatgcatc ttacaataac
tactataatc attcatatca atacaataac 300tatacaaaca atagccaaac agcaacaaat
aactattata ctggtggttc aggtgcaagt 360tatagcacaa caagtaataa tgttcatgtg
actacaactg cagcgccatc ttcaaatggt 420cgttcaattt ctaatggtta tgcatcagga
agtaacttat atacttcagg acaatgtact 480tattatgtat ttgatcgtgt tggtgggaaa
attggttcaa catggggtaa cgcaagtaat 540tgggctaacg cagctgcatc atctggctat
acagtgaaca atacaccaaa agttggtgct 600atcatgcaaa caacacaagg ctattacggt
catgttgctt acgttgaagg cgttaacagc 660aacggttctg ttcgtgtttc agaaatgaac
tatggacatg gtgctggtgt ggttacgtct 720cgtacaattt cagcaaacca agcaggttca
tataatttca ttcattaa 76839804DNAStaphylococcus sp.
39atgaagaaaa tcgctacagc tactatcgca actgcaggat tcgctacaat cgcaattgca
60tcaggaaatc aagctcatgc ttctgagcaa gataactacg gttataatcc aaacgaccca
120acatcatata gctatactta cactattgat gcacaaggta actaccatta cacatggaaa
180ggtaactggc atccaagtca attaaaccaa gataatggct actacagcta ttactactac
240aatggctaca ataactacaa caattacaac aatggttata gctacaataa ttacagccgt
300tacaacaact actcaaataa taatcaatca tataactaca ataactataa tagttacaac
360acaaacagct accgtactgg tggtttaggt gcaagctaca gcacttcaag caacaatgtt
420caagtaacta caactatggc tccatcatca aatggccgtt caatctcaag tggttatact
480tcaggacgta acttatacac ttctggtcaa tgtacatact acgtatttga tcgtgtaggt
540ggtaaaatcg gttcaacttg gggcaatgca agtaactggg ctaacgcagc tgcaagagct
600ggttacacag tgaacaatac accaaaagct ggtgcaatta tgcaaacaac tcaaggtgca
660tacggtcacg ttgcatacgt tgaaagtgtt aacagcaatg gttcagtaag agtttcagaa
720atgaactatg gttatggccc aggtgttgta acttcacgta caatctcagc tagccaagct
780gctggttata acttcattca ctaa
80440774DNAStaphylococcus sp. 40atgaaaaaaa tcgctacagc tacaattgca
actgcaggaa tcgctacttt cgcatttgca 60caccatgacg cacaagcagc agaacaaaat
aatgatgggt acaatccaaa cgacccttat 120tcatatagct acacttacac aatcgatgct
gaaggtaact accactacac ttggaaaggt 180aactggagtc cagatcgtgt aaatacttca
tataactata ataattataa taactacaac 240tactatggtt acaataacta tagcaactac
aataactaca gtaattacaa caattacaac 300aactatcaat caaacaacac gcaatcacaa
agaacaactc aaccgactgg tggtttaggc 360gcaagctatt caacatcaag tagtaatgtt
cacgttacaa caacttctgc gccatcatca 420aacggtgtat ctttatcaaa cgctcgctca
gcatctggta acttatacac ttcaggtcaa 480tgtacatatt atgtatttga cagagtaggt
ggcaaaatcg gttcaacgtg gggtaacgca 540aacaactggg caaacgctgc agcacgttct
ggttacacag taaacaattc gcctgctaaa 600ggtgcaatct tacaaacgtc acaaggtgca
tacggacacg tagcatacgt tgaaggtgta 660aacagcaatg gttcaatcag agtttcagaa
atgaactacg gtcacggtgc aggtgttgtc 720acttcacgta caatctctgc gagccaagct
gcttcatata actatattca ctaa 77441930DNAStaphylococcus sp.
41atgaaaaaat tagtaccttt attattagcc ttattacttc tagttgctgc atgtggtact
60ggtggtaaac aaagcagtga taagtcaaat ggcaaattaa aagtagtaac gacgaattca
120attttatatg atatggctaa aaatgttggt ggagacaacg tcgatattca tagtattgta
180cctgttggtc aagatcctca tgaatatgaa gttaaaccta aagatattaa aaagttaact
240gacgctgacg ttattttata caacggatta aatttagaga ctggtaacgg ttggtttgaa
300aaagccttag aacaggctgg taaatcatta aaagataaaa aagttatcgc agtatcaaaa
360gatgttaaac ctatctattt aaacggtgaa gaaggcaaca aagataaaca agatccacac
420gcatggttaa gtttagataa tggtattaaa tacgtaaaaa caattcaaca aacatttatc
480gataacgaca aaaaacataa agcagattat gaaaagcaag gtaacaaata cattgctcaa
540ttggaaaaat taaataatga cagtaaagac aaatttaatg acattccaaa agaacaacgt
600gccatgatta caagtgaagg tgccttcaag tacttctcaa aacaatacgg tattacacca
660ggttatattt gggaaattaa cactgaaaaa caaggtacac ctgaacaaat gagacaagct
720attgagtttg ttaaaaagca caaattaaaa cacttattag tagaaacaag tgttgataag
780aaagcaatgg aaagtttatc tgaagaaacg aagaaagata tctttggtga agtgtacaca
840gattcaatcg gtaaagaagg cactaaaggt gactcttact acaaaatgat gaaatcaaat
900attgaaactg tacacggaag catgaaataa
93042930DNAStaphylococcus sp. 42gtgaaaaaaa ttctcgcttt agcaatagca
tttttaatta tccttgccgc atgtgggaat 60cacagtaacc atgaacatca ctcacatgaa
ggaaaattaa aagttgtaac tacaaactct 120attctctatg acatggttaa acgtgtcggt
ggaaataagg tcgatgttca tagcatcgtt 180ccagtaggac aagacccaca tgaatatgag
gttaaaccta aagatattaa agcattaaca 240gatgctgacg ttgtatttta taacggttta
aacctagaaa ctggaaatgg ttggtttgaa 300aaagcacttg accaagcagg aaaatcaaca
aaagataaaa atgtgatagc agcatcaaat 360aatgttaaac caatatactt aaatggtgag
gaaggtaaca aaaacaaaca agatccacat 420gcatggttaa gtttagagaa tggaattaaa
tacgtaaaaa caatacaaaa atcactagaa 480catcatgata aaaaagataa gtctacatat
gaaaaacaag ggaatgcata tatatcaaaa 540ttagaagaac ttaataaaga tagtaaaaat
aaatttgatg acatacccaa aaatcaacgt 600gccatgatga caagtgaagg tgcatttaaa
tattttgctc aacaattcga tgttaaacca 660ggttatattt gggagataaa cacagaaaaa
caaggtacac ctggtcaaat gaaacaagcc 720attaaatttg ttaaagataa tcatttaaaa
catttattag tcgaaacaag cgtagataaa 780aaagctatgc aaagtttatc agaagaaact
aagaaagata tttatggtga agtatttacc 840gactctatag gtaaggaagg tactaaaggt
gactcatact ataaaatgat gaaatctaat 900attgatacaa tacatggtag tatgaaataa
93043702DNAStaphylococcus sp.
43atgaaaaaga caattatggc atcatcatta gcagtggcat taggtgtaac aggttacgca
60gcaggtacag gacatcaagc acacgctgct gaagtaaacg ttgatcaagc acacttagtt
120gacttagcgc ataatcacca agatcaatta aatgcagctc caatcaaaga tggtgcatat
180gacatccact ttgtaaaaga tggtttccaa tataacttta cttcaaatgg tactacatgg
240tcatggagct atgaagcagc taatggtcaa actgctggtt tctcaaacgt tgcaggtgca
300gactacacta cttcatacaa ccaaggttca gatgtacaat cagtaagcta caatgcacaa
360tcaagtaact caaacgttga agctgtttca gctccaactt accataacta cagcacttca
420actacttcaa gttcagtgag attaagcaat ggtaatactg caggtgctac tggttcatca
480gcagctcaaa tcatggctca acgtactggt gtttcagctt ctacatgggc tgcaatcatc
540gctcgtgaat caaatggtca agtaaatgct tacaacccat caggtgcttc aggtttattc
600caaactatgc caggttgggg tccgacaaac actgttgacc aacaaatcaa cgcagctgtt
660aaagcataca aagcacaagg tttaggtgct tggggattct aa
70244708DNAStaphylococcus sp. 44atgaaaaaaa cagttatcgc ttctacatta
gcagtatctt taggaattgc aggttacggt 60ttatcaggac atgaagcaca cgcttcagaa
actacaaacg ttgataaagc acacttagta 120gatttagcac aacataatcc tgaagaatta
aatgctaaac cagttcaagc tggtgcttac 180gatattcatt tcgtagacaa tggataccaa
tacaacttca cttcaaatgg ttctgaatgg 240tcatggagct acgctgtagc tggttcagat
gctgattaca cagaatcatc atcaaaccaa 300gaagtaagtg caaatacaca atctagtaac
acaaatgtac aagctgtttc agctccaact 360tcttcagaaa gtcgtagcta cagcacatca
actacttcat actcagcacc aagccataac 420tacagctctc acagtagttc agtaagatta
tcaaatggta atactgctgg ttctgtaggt 480tcatatgctg ctgctcaaat ggctgcacgt
actggtgtat ctgcttcaac atgggaacac 540atcattgcta gagaatcaaa tggtcaatta
catgcacgta atgcttcagg tgctgctgga 600ttattccaaa ctatgccagg ttggggttca
actggttcag taaatgatca aatcaatgcc 660gcttataaag catataaagc acaaggttta
tctgcttggg gtatgtaa 7084511670DNAStaphylococcus sp.
45gtgaattatc gtgataaaat tcaaaagttt agtattcgta aatatacagt tggtacattt
60tcaactgtca ttgcgacatt ggtattttta ggattcaata catcacaagc acatgctgct
120gaaacaaatc aaccagcaag cgtggttaaa cagaaacaac aaagtaataa tgaacagact
180gagaatcgag aatctcaagt acaaaattct caaaattcac aaaatagtca atcattatcc
240gctactcatg aaaatgagca accaaataat agtcaagcta atttagtaaa tcaaaaagta
300gcgcaatcat ctactactaa tgatgaacaa ccagcatctc aaaatgtaaa tacaaagaaa
360gattcggcaa cggctgcgac aacacaacca gataaagaag aaagtaagca taaacaaaac
420gaaagtcaat ctgctaataa aaatggaaac gacaatagag cggctcatgt agaaaatcat
480gaagcaaatg tagtaacagc ttcagattca tctgataatg gtaacgtaca acatgaccga
540aatgaattac aagcattttt tgatgcaaat tatcatgatt atcgctttat tgaccgtgaa
600aatgcagatt ctggcacatt taactatgta aaaggcattt ttgacaagat taatacttta
660ttaggcagta atgatccaat taacaataaa gacttgcaac ttgcatacaa agaattggaa
720caagctgttg ctttaattcg tacaatgcct caacgtcaac aaactagccg tcgatcaaac
780agaattcaaa cgcgttctgt tgagtctaga gctgcagagc ctagatcagt atcagactat
840caaaatgcaa attcatcata ttatgttgaa aatgctaatg atggttcagg atatcctgta
900ggtacatata tcaatgcttc tagtaaaggg gcgccatata atttaccaac tacaccatgg
960aatacattga aggcctctga ctcaaaggaa attgctctta tgacagcgaa acaaactgga
1020gatggctacc aatgggttat taagtttaat aaaggacatg ctccacatca aaatatgatt
1080ttctggtttg cattaccagc agaccaagtg ccagtaggaa gaactgactt tgtaacagtt
1140aattcagatg gaacaaatgt acaatggagt catggagcag gagcaggtgc aaataaacca
1200cttcaacaaa tgtgggaata tggagtaaat gatcctgatc gttcacatga ctttaaaata
1260agaaatagaa gtggccaagt aatatatagc tggccaactg tccatgttta ttctttagaa
1320gatttatcta gagcgagtga ttattttagt gaagctggag cgacacctgc tactaaagca
1380tttggtagac aaaattttga atatattaat ggtcaaaaac ctgctgaatc accgggtgtt
1440cctaaagttt atactttcat cggtcaaggt gatgcaagtt atacaatttc atttaaaaca
1500caaggtccaa ctgttaataa attgtattat gcagcaggtg ggcgtgcttt agagtacaat
1560caattattta tgtacagtca actatacgtc gaatcaacgc aagaccatca acaacgtctt
1620aatggtttaa gacaagtggt taatcgtaca tatcgcatag gtacaactaa acgtgtagaa
1680gtgagtcaag gaaatgtaca aacgaaaaag gtattagaaa gtacaaacct aaatatagat
1740gattttgttg atgatccttt aagttatgtt aagacgccga gtaataaagt gttaggtttt
1800tacccaacta atgcaaatac taacgctttt agaccggggg gcgttcaaga attaaatgaa
1860tatcaattaa gtcaattatt tactgatcaa aaattacaag aagcagcaag aactagaaac
1920ccaataagat taatgattgg tttcgactat cctgatggtt atggtaatag tgaaacttta
1980gttcctgtta acttaacggt attacctgaa atccaacata atattaaatt ctttaaaaat
2040gacgatactc aaaatattgc tgaaaaacca ttttcaaaac aagctgggca tccagttttc
2100tatgtatatg caggtaacca agggaatgct tccgtgaatt taggtggtag cgtaacatct
2160attcaaccat tacgtattaa tttaacaagt aatgagaatt ttacagataa agattggcaa
2220attacaggta ttccgcgtac attacacatt gaaaactcga caaatagaac taataatgct
2280agagaacgta acattgaact tgttggtaat ttattaccag gggattactt tggtacgata
2340cgttttggac gtaaagaaca attatttgaa attcgtgtta aaccacatac accaacaatt
2400acaacgacag ctgagcaatt aagaggtaca gcattacaaa aagtgcctgt taatatttcg
2460ggaataccgt tggatccatc ggcattggtt tatttagttg caccaacaaa tcaaactacg
2520aatggtggta gtgaggcaga tcaaatacca tctggttata cgatacttgc gactggtaca
2580cctgatgggg tgcataatac aattactata cgaccgcaag attatgttgt attcatacca
2640cctgtaggta aacaaattag agcagtagtt tattataata aagtagttgc atctaatatg
2700agtaatgctg ttactatttt gccagatgac attccaccaa caatcaataa tcctgttgga
2760ataaatgcca aatactatcg aggcgacgaa gtcaacttta caatgggagt ctctgataga
2820cattctggta taaaaaatac aactattact actttgccaa gtggttggac atcaaattta
2880actaaatccg acaacaaaaa cggctcatta gctattacag gtagagtctc tatgaatcag
2940gcatttaaca gtgatattac atttaaagta tcagcgacag acaatgtcaa taatacgaca
3000aatgatagtc aatctaaaca tgtgtcaatt catgtaggta aaattagtga agatgctcat
3060ccgattgtat taggaaatac tgagaaagtt gtagtagtca atccgactgc tgtatctaat
3120gatgaaaagc aaagcataat tactgccttt atgaataaaa accaaaatat aagaggatat
3180ttagcatcaa ctgatccagt aactgtcgat aataatggta acgtcacatt acattaccgt
3240gatggctcat caacaacgct tgatgctaca aatgtgatga catacgaacc agttgtgaaa
3300tctgaatatc aaactgccaa tgctgctaaa acagcaacgg taacgattgc taaaggacaa
3360tcatttaata ttggtgatat taaacaatat tttactttaa gtaatggaca agctattcca
3420aatggcacat ttacaaatat tacatctgat agaactattc caactgcaca agaagttagt
3480caaatgaatg caggtacgca gttatatcat atagttgctt caaatgcata tcataaagac
3540actgaagatt tctatattag tttaaaaatc gttgatgtga aacaacctga aggcgatcaa
3600cgtgtctatc gtacgtcaac atatgattta accactgatg aaatctcaaa agtaaaacaa
3660gcttttatta atgcaaatag agatgtaatt acgcttgccg aaggtgatat ttcagttaca
3720aatacaccta atggtgctaa tgtaagtact attacagtaa atattaataa aggtcgatta
3780acgaaatcat tcgcgtctaa cctagctaat atgaatttct tgcgttgggt taatttccca
3840caagattata cagtgacatg gacgaatgca aaaattgcaa acagaccaac agatggtggt
3900ttatcatggt ccgatgacca taaatcttta atttatcgtt atgatgctac attaggcaca
3960caaattacaa ctaatgatat tttaacgatg ctaaaagcga ctactacagt gcctggattg
4020cgtaataata ttactggtaa tgaaaaagca caagcagaag caggtggaag accaaactat
4080agaacaactg gttattcaca atcaaatgcg acaactgatg gtcaacgtca atttacgttg
4140aatggtcaag tgattcaaat attagacatc atcaaccctt caaacggtta tggtgggcaa
4200cctgttacaa attcaaatac tcgtgcaaac catagtaact caactgttgt taacgtaaac
4260gaaccggcag ctaatggtgc tggcgcattt acaattgacc acgttgtaaa aagtaattct
4320acacataatg caagtgatgc agtttataaa gcgcagttat acttaacgcc atatggtcca
4380aaacaatatg ttgaacattt aaatcaaaat acaggaaata ctactgacgc tattaacatt
4440tattttgtac caagtgactt agtgaatcca acaatttcag taggtaatta cactaatcat
4500caagtgttct caggtgaaac atttacaaat acgattacag cgaatgataa ctttggtgtg
4560caatcggtaa ctgtaccaaa tacatcacaa attacaggta ctgttgataa taaccatcaa
4620catgtttctg caacggcacc aaatgtgaca tcagcaacta gtaagacaat caatttatta
4680gcaactgata caagtggtaa tacagctaca acttcattca atgtaacagt gaaacctttg
4740cgtgataaat atcgagttgg tacttcatca acggctgcta atcctgttag aattgccaat
4800atttcgaata atgcgacagt atcacaagct gatcaaacga caattattaa ttcgttaacg
4860tttacaagta atgcaccaaa tagaaactat gcaacagcaa gcgcaaatga aatcactagt
4920aaaacagtta gtaatgtcag tcgtactgga aataatgcca atgtcacagt aactgttact
4980catcaagatg gaacaacatc aacagtgact gtacctgtaa agcatgtcat tccagaaatc
5040gttgcacatt cgcattacac tgtacaaggc caagacttcc cagcaggtaa tggttctagt
5100gcagcagatt actttaagtt atctaatggt agtgccattc cagatgcaac gattacatgg
5160gtaagtggac aagcgccaaa taaagataat acacgtattg gtgaagatat aacagtaact
5220gcacatatct taattgatgg cgaaacaacg ccgattacga aaacagcaac atataaagta
5280gtaagaactg taccgaaaca tgtctttgaa acagccagag gtgttttata cccaggtgtt
5340tcagatatgt atgatgcgaa acaatatgtt aagccagtaa ataattcttg gtcgacaaat
5400gcgcaacata tgaattttca atttgttgga acatatggtc ctaacaaaga tgttgtaggt
5460atatcaacgc gtcttattag agtgacttat gataatagac aaactgaaga tttaactatt
5520ttatctaaag ttaaacctga cccaccaaga attgacgcaa actctgtgac atataaagca
5580ggtcttacaa accaagaaat taaagttaat aacgtattaa ataactcgtc agtaaaatta
5640tttaaagcag ataatacacc attaaatgtc acaaatatta ctcatggtag tggttttagt
5700tcggttgtga cagtaagtga cgcgttacca aatggcggaa ttaaagcaaa atcttcaatt
5760tcaatgaaca atgtgacgta tacgacgcaa gacgaacatg gtcaagttgt tacagtaaca
5820agaaatgaat ctgttgattc aaatgatagt gcttctgtta cagtaacacc acaattacaa
5880gcaactactg aaggcgctgt atttattaaa ggtggcgacg gttttgattt cggtcatgta
5940gaacgattta ttcaaaatcc gccacatggg gcaacggtcg catggcatga tagtccagat
6000acatggaaga atacagtcgg caacacacat aaaactgcgg ttgtaacatt acctagtggt
6060caaggtacgc gtaatgttga agttccagtc aaagtttatc cagttgctaa tgctaaggcg
6120ccatcacgtg atgtgaaagg tcaaaatttg acacatggta caaacgctat tgattacatt
6180acatttgatc caaatactaa tacgaatggt attacagcag catgggcaaa tagacaacaa
6240ccaaataacc agcaagcagg cgttcaacat ttaaatgtcg atgtcacata tccaggtatt
6300tcagctgcta aacgagttcc tgtaactgtg aacgtatatc aatttgaatt ccctcaaact
6360acttatacaa caacagttgg tggcacttta gcaagtggta cgcaagcatc aggatatgca
6420catatgcaaa acgcttcagg tttaccaaca gatggattta cgtataaatg gaatcgtgat
6480actacgggta caaacgatgc aaactgggca gcaatgaata aaccaaatac tgcacaagtc
6540gttaatgcaa aatatgatgt catctataat ggacatacat ttgcaacatc tttaccagcg
6600aaatttgtag taaaagatgt tcaaccagcg aaaccaactg tcactgaaac agcggcagga
6660gcgattacaa ttgcacctgg tgcgaaccaa acagtcaata ctcatgctgg taatgttacg
6720acatatgctg acaaattagt tattaaacgt aatggaaatg ttgtaacgac atttacacgt
6780cgtaataata cgagcccatg ggtgaaagaa gcatcagcag ataatgtaac aggtattgtt
6840ggaactaata atggtattac tgtggcagca ggtactttca atcctgctga tacaattcaa
6900gttgttgcaa cacaaggtag tggcgaaaca atcagtgacg agcaacgtag tgatgatttc
6960acagttgtcg caccacaacc gaaccaagcg actacgaaaa tttggcaaaa tggtcatatt
7020gatatcacgc ctaataatcc atcaggacat ttaattaatc caacacaagc aatggatatt
7080gcttacactg aaaaagtggg taatggtgca gaacatagta agacaattaa tgttgttcgt
7140ggtcaaaata atcaatggac aattgcgaat aagcctgact atgtaacgtt agatgcacaa
7200actggtaaag tgacgttcaa tgccaatact ataaaaccaa attcatcaat cacaattact
7260ccgaaagcag gtacaggtca ctcagtaagt agtaatccaa gtacattaac tgcaccggca
7320gctcatactg tcaacacaac tgaaattgtg aaagattatg gttcaaatgt aacagcagct
7380gaaattaaca atgcagttca agttgctaat aaacgtactg caacgattaa aaatggcaca
7440gcaatgccta ctaatttagc tggtggtagc acaacgacga ttcctgtgac agtaacttac
7500aatgatggta gtactgaaga agtacaagag tccattttca caaaagcgga taaacgtgag
7560ttaatcacag ctaaaaatca tttagatgat ccagtaagca ctgaaggtaa aaagccaggt
7620acaattacgc agtacaataa tgcaatgcat aatgcgcaac aacaaatcaa taccgcgaaa
7680acagaagcac aacaagtgat taataatgag cgtgcaacac cacaacaagt ttctgacgca
7740ctaactaaag ttcgtgcagc acaaactaag attgatcaag ctaaagcatt acttcaaaat
7800aaagaagata atagccaatt agtaacgtct aaaaataact tacaaagttc tgtgaaccaa
7860gtaccatcaa ctgctggtat gacgcaacaa agtattgata actataatgc gaagaagcgt
7920gaagcagaaa ctgaaataac tgcagctcaa cgtgttattg acaatggcga tgcaactgca
7980caacaaattt cagatgaaaa acatcgtgtc gataacgcat taacagcatt aaaccaagcg
8040aaacatgatt taactgcaga tacacatgcc ttagagcaag cagtgcaaca attgaatcgc
8100acaggtacaa cgactggtaa gaagccggca agtattactg cttacaataa ttcgattcgt
8160gcacttcaaa gtgacttaac aagtgctaaa aatagcgcta atgctatcat tcagaagcca
8220ataagaacag tgcaagaggt acaatctgcg ttaacaaatg taaatcgtgt caatgagcga
8280ttaacgcaag caattaatca attagtacct ttagctgata atagtgcttt aagaactgct
8340aagacgaaac ttgatgaaga aatcaataaa tcagtaacta ctgatggtat gacacaatca
8400tcaatccaag catatgaaaa tgctaaacgt gcaggtcaaa cagaaacaac aaatgcacaa
8460aatgttatta acaatggtga cgcgacagac caacaaattg ccgcagaaaa aacaaaagta
8520gaagaaaaat ataatagctt aaaacaagca attgctggat taacaccaga cttggcacca
8580ttacaaactg caaaaactca gttgcaaaat gatattgatc agccaacgag tacgactggt
8640atgacaagcg catctgttgc tgcatttaat gacaaacttt cagcagctag aactaaaatt
8700caagaaattg atcgcgtact agcatctcat ccagatgtag caacgattcg tcaaaacgtg
8760acagcagcga atgctgctaa aacagcactt gatcaagcgc gcaatggctt aacagtcgat
8820aaagcacctt tagaaaatgc gaaaaatcaa ctacaacata gtattgatac gcaaacaagt
8880acaactggta tgacacaaga ctctataaat gcatacaatg cgaagttaac agctgcacgt
8940aataaggttc aacaaatcaa tcaagtatta gcaggttcac ctactgtaga tcaaattaat
9000acaaatacgt ctgcagcaaa tcaagcgaaa tctgatttag atcatgcacg tcaagcgtta
9060acaccagata aagcgccgct tcaaaatgcg aaaacgcaat tagaacaaag cattaatcaa
9120ccaacagata caacaggtat gacaaccgct tcgttaaatg catacaacca aaaattacaa
9180gcagcacgtc aaaagttaac tgaaattaat caagtgttga atggcaaccc aactgtccaa
9240aatatcaatg ataaagtggc agaggcaaac caagctaagg atcaattaaa tacagcacgt
9300caaggtttaa cattagatag acagccagcg ttaacaacat tacatggtgc atctaactta
9360aaccaagcac aacaaaataa tttcacgcaa caaattaatg ctgctcaaaa tcatgctgcg
9420cttgaaacaa ttaagtctaa cattacggct ttaaatactg cgatgacgaa attaaaagac
9480agtgttgcgg ataataatac aattaaatca ggtcaaaatt acactgacgc aacaccagct
9540aataaacaag cctatgataa tgcagttaat gcggctaaag gtgtcattgg agaaacgact
9600aatccaacga tggatgttaa cacagtgaac caaaaagcag catctgttaa atcgacgaaa
9660gatgctttag atggtcaaca aaacttacaa cgtgcgaaaa cagaagcaac aaatgcgatt
9720acgcatgcaa gtgatttaaa ccaagcacaa aagaatgcat taacacaaca agtgaatagt
9780gcacaaaacg tgcaagcagt aaatgatatt aaacaaacga ctcaaagctt aaatactgct
9840atgacaggtt taaaacgtgg cgttgctaat cataaccaag tcgtacaaag tgataattat
9900gtcaacgcag atactaataa gaaaaatgat tacaacaatg catacaacca tgcgaatgac
9960attattaatg gtaatgcaca acatccagtt ataacaccaa gtgatgttaa caatgcttta
10020tcaaatgtca caagtaaaga acatgcattg aatggtgaag ctaagttaaa tgctgcgaaa
10080caagaagcga atactgcatt aggtcattta aacaatttaa ataatgtaca acgtcaaaac
10140ttacaatcgc aaattaatgg tgcgcatcaa attgatgcag ttaatacaat taagcaaaat
10200gcaacaaact tgaatagtgc aatgggtaac ttaagacaag ctgttgcaga taaagatcaa
10260gtgaaacgta cagaagatta tgcggatgca gatacagcta aacaaaatgc atataacagt
10320gcagtttcaa gtgctgaaac aattattaat caaacagcta atccgacaat gtctgttgat
10380gatgttaatc gtgcaacttc agctgttact actaataaaa atgcattaaa tggtgatgaa
10440aaattagtac aatctaaaac agatgctgca agagcaattg atgcattacc acatttaaat
10500aatgcacaaa aagcagatgt taaatctaaa attaatgctg catcaaatat tgctggtgta
10560aataccgtta aacaacaagg tacagattta aatacagcga tgggtaactt gcagggtgca
10620atcaatgatg aacaaacgac gcttaatagt caaaattatc aagatgcgac acctagtaag
10680aaaacagcat acacaaatgc ggtgcaagct gcgaaagata ttttaaataa atcaaatggt
10740caaaataaaa cgaaagatca agttactgaa gcgatgaatc aagtgaattc ggctaaaaat
10800aacttagatg gtacgcgttt attagatcaa gcgaagcaaa cagcgaaaca gcagttaaat
10860aatatgacgc atttaacaac tgcacaaaaa acgaatttaa caaatcaaat taatagtggt
10920actactgttg ctggtgttca tacggttcaa tcaaatgcca acacattaga tcaagcgatg
10980aatacgttaa gacaaagtat tgctaacaat gatgcgacta aagcaagtga agattacgta
11040gatgctaata atgataagca aacagcatat aacaacgcgg tagctgctgc tgaaacgatt
11100attaatgcga atagtaatcc agaaatgaat ccaagtacga ttacacaaaa agcagagcaa
11160gtgaatagtt ctaaaacggc acttaacggt gatgaaaact tagctacggc aaaacaaaat
11220gcgaaaacgt acttaaacac attaacgagt attacagatg ctcaaaagaa caatttgatt
11280agtcaaatta gtagtgcgac aagagtgagt ggtgttgata ctgtaaaaca aaatgcacaa
11340catttagatc aagctatggc taacttacaa aatggtatta acaacgaatc tcaagtgaaa
11400tcatctgaga aatatcgtga tgctgataca aataaacaac aagagtatga taatgctatt
11460actgcagcga aagcgatttt aaataaatcg acaggtccaa acactgcgca aaatgcagtt
11520gaagcagcat tgcaacgtgt taatactgcg aaagatgcat tgaatggtga tgcaaaatta
11580attgcagctc aaaacgcagc gaaacaacat ttaggtactt taacgcatat cactacagca
11640caacgcaatg atttaacaaa tcaaatttca
116704620139DNAStaphylococcus sp. 46atgggtaact tacaaacggc tatcaacgat
aagtcaggaa cattagcgag ccaaaacttc 60ttggatgctg atgagcaaaa acgtaatgct
tacaatcaag ctatatcagc tgccgaaacc 120attttaaata aacaaactgg accgaataca
gcgaaaacag cggttgaaca agcacttaat 180aatgttaata gtgcgaaaca tgcattaaat
ggtacgcaaa acttaaataa tgcgaaacaa 240gcagcgatta cagcaattaa tggcgcatct
gatttaaatc aaaaacaaaa agatgcatta 300aaagcacaag ctaatggtgc tcaacgcgta
tctaatgcaa atgatgtaca acgtaatgcg 360actgaactga acacggcaat gggtcaatta
caacatgcca tcgcagataa gacgaatacg 420ttagcaagca gtaaatatgt caacgccgat
agcactaaac aaaatgctta cacaactaaa 480gttaccaatg ctgaacatat tattagcggt
acgccaacgg ttgttacaac accttcagaa 540gtaacagctg cagctaatca agtaaacagc
gcgaaacaag aattaaatgg tgacgaaaga 600ttacgtgttg caaaacaaaa cgccaatact
gctattgatg cattaacgca attaaatact 660cctcaaaaag ctaaattaaa agaacaagtg
ggacaagcca atagattaga agacgtacaa 720tctgttcaaa caaatggaca atcattgaac
aatgcaatga aaggcttaag agatagtatt 780gctaacgaaa caacagtcaa agcaagtcaa
aactatacag acgcaagtcc gaataaccaa 840tcaacatata atagcgctgt gtcaaatgcg
aaaggtatca ttaatcaaac taacaatcca 900actatggata ctagtgcgat tacccaagct
acaacacaag tgaataatgc taaaaatggt 960ttaaacggtg ctgaaaactt aagaaatgca
caaaacactg ctaagcaaaa cttaaatacg 1020ttatcacact taacaaataa ccaaaaatct
gcaatctcat cacaaattga tcgtgcaggt 1080catgtgagtg aggtaacagc tgctaaaaat
gcagcaactg agttaaacgc gcaaatgggc 1140aacttggaac aagctatcca tgatcaaaac
acagttaaac aaggtgttaa cttcactgat 1200gcagataaag ctaaacgtga tgcttataca
aatgcggtaa gcagagcaga aacaattctg 1260aataaaacgc aaggtgcaaa tacgtctaaa
caagatgttg aagcggctat tcaaaatgtt 1320acaagtgcta aaaatgcatt gaatggtgat
caaaacgtta caaatgcgaa gaatgcagct 1380aaaaatgcat taaataactt aacgtcaatt
aataatgcac aaaaacgtga cttaacaact 1440aaaattgatc aagcaacaac agtagctggt
gttgaagcgg tatctaatac aggtacacaa 1500ttgaatacag cgatggctaa cttgcaaaat
ggtattaatg ataaagcgaa tactttagcg 1560agcgaaaact atcatgatgc tgattcagat
aagaaaactg cttatactca agccgttacg 1620aacgcagaaa atattttaaa taaaaatagt
ggatcaaatt tagataaagc tgccgttgaa 1680aacgcgttgt cacaagtgac aaatgcgaaa
ggtgccctaa atggtaacca taatttagag 1740caagctaaat caaatgcaaa cactactata
aacggccttc aacatttaac aacagcacaa 1800aaagataaat tgaaacaaca agtgcaacaa
gcacaaaatg ttgcaggtgt agatactgtt 1860aaatcaagtg ccaacacatt aaatggtgct
atgggtacgt taagaaatag catacaagat 1920aacacagcta cgaaaaatgg ccaaaactat
cttgatgcta cagaacgtaa caaaacaaac 1980tataacaatg ctgttgatag tgctaatggt
gtcattaatg caacaagcaa tccaaatatg 2040gatgctaatg caattaacca aatcgctaca
caagtgacat caacgaaaaa tgcattagat 2100ggtacacata atttaacgca agcgaaacaa
acagcaacaa atgccatcga tggtgctact 2160aacttaaata aagcgcaaaa agatgcgtta
aaagcacaag ttacaagtgc gcaacgtgtt 2220gcaaatgtaa caagtatcca acaaactgca
aatgaactta atacagctat gggtcaatta 2280caacatggta ttgatgatga aaatgcaaca
aaacaaactc aaaaatatcg tgacgctgaa 2340caaagtaaga aaactgctta tgatcaagct
gtagctgctg cgaaagcaat tttaaataaa 2400caaacaggtt ccaattcaga taaagcagca
gttgaccgtg cattacaaca agtaacaagt 2460acgaaagatg cattgaatgg ggatgctaaa
ctggcagaag cgaaagcggc agctagacaa 2520aacttaggta ctttaaacca tattacgaat
gcacaacgta ctgcgttaga aggtcaaatc 2580aatcaagcga cgactgttga tggcgttaat
actgtaaaaa caaatgccaa tacattagac 2640ggcgctatga atagcttaca aggtgcaatc
aatgataaag atgcgacatt aagaaatcaa 2700aattatcttg atgcagatga atcaaaacga
aatgcatata cgcaagctgt cacagcggct 2760gaaggcattt taaataaaca aacaggtggt
aacacatcta aagcagacgt tgataatgca 2820ttaaatgcag ttacaagagc gaaagcggct
ttaaatggtg ctgaaaactt aagaaatgcg 2880aaaacttcag caacaaatac gattaatggt
ttacctaact taacacaatt acaaaaagac 2940aacttgaagc atcaagttga acaagcgcaa
aatgtagttg gtgtaaatgg tgttaaagat 3000aaaggtaata cattaaatac tgccatgggt
gcattacgta caagtatcca aaatgataat 3060acgacgaaaa caagtcaaaa ttatcttgat
gcatctgata gcaacaaaaa taattacaat 3120actgctgtaa ataatgcaaa tggtgttatt
aatgcaacga acaatccaaa tatggatgct 3180aatgcgatta atgacatggc aaatcaagtc
aatacaacaa aagcagcgtt aaatggtgca 3240caaaacttag ctcaagctaa aacaaatgcg
acgaacacaa ttaacaacgc gcaagactta 3300aaccaaaaac aaaaagatgc attaaaaaca
caagttaaca atgcacaacg tgtatctgat 3360gcaaataacg ttcaacatac agctactgaa
ttgaacggtg cgatgacagc acttaaagca 3420gctattgcgg ataaagaaag aacaaaagca
agcggtaatt atgtcaatgc tgatcaagaa 3480aaacgtcaag cgtatgattc aaaagtgact
aacgctgaaa atatcattaa tggtacacca 3540aatgcgacat taacagtcaa tgacgtaaat
agtgcggcat cacaagtcaa tgcggctaaa 3600acagcattaa atggtgataa caacttacgt
gtagcgaaag agcatgctaa caatacaatt 3660gacggcttag cacaattgaa taatgtacaa
aaagcaaaat taaaagaaca agttcaaagt 3720gcaactacat tagatggtgt tcaaactgtt
aaaaatagtt ctcaaacgtt gaatacagcg 3780atgaaaggct taagagatag tattgcgaat
gaagcaacga ttaaagcagg tcaaaactac 3840actgacgcaa gtccaaataa tcgtaacgag
tacgacagcg cagttactgc agcaaaagca 3900atcattaatc aaacatcgaa cccaacgatg
gaaccaaata ctattacgca agcaacatca 3960caagtgacaa ctaaagaaca tgcattaaat
ggtgcgcaaa acttagctca agctaagaca 4020acagcgaaaa acaacttgaa taacttaaca
tcaattaaca atgcacaaaa agatgcgtta 4080acgcgtaaca ttgatggtgc aactacagta
gctggtgtaa atcaagaaac tgcaaaagca 4140acagaattaa ataacgcaat gcacagttta
caaaatggta tcaatgatga gacacaaaca 4200aaacaaactc agaaatacct agatgctgag
ccaagtaaga aatcagctta tgatcaagca 4260gtaaatgcag caaaagcaat tttaacaaaa
gctagtggtc aaaatgtaga caaagcagca 4320gttgaacaag cattacaaaa tgtgaacagt
acgaagacgg cgttgaacgg tgatgcgaaa 4380ttaaatgaag ctaaagctgc tgcgaaacaa
acgttaggta cattaacaca cattaataat 4440gcacaacgta atgcgttaga taatgaaatt
acacaagcaa caaatgttga aggtgttaat 4500acagttaaag ccaaagcgca acaattagat
ggtgctatgg gtcaattaga aacatcaatt 4560cgtgataaag acacgacgtt acaaagtcaa
aattatcaag atgctgatga tgctaaacga 4620acggcttatt ctcaagcagt aaatgcagca
gcaactattt taaataaaac agctggagga 4680aatacaccta aagcagatgt cgaaagagca
atgcaagctg ttacacaagc caatactgca 4740ttaaacggta ttcaaaactt agaacgtgcg
aaacaggctg cgaacacagc gattacaaat 4800gcttcggact taaatacaaa acaaaaagaa
gcattgaaag cacaagtaac aagtgcagga 4860cgcgtatctg cagcaaatgg tgttgaacat
actgcgactg aattaaatac tgcgatgaca 4920gctttaaaac gtgccattgc tgataaagct
gacacaaaag ctagtggtaa ttatgtcaat 4980gctgatgcga ataaacgcca agcatatgat
gaaaaagtga cagctgcaga acatatcgtt 5040agtggtacac caacaccaac gttaacacca
tcagatgtta caaatgcagc aacgcaagta 5100acgaatgcga agacgcagtt aaacggtaat
cataatttag aagtagcgaa acaaaatgct 5160aacacagcaa ttgatggttt aacttcttta
aatggtccgc aaaaagcaaa acttaaagaa 5220caagtgggtc aagcgacgac gttgccaaat
gttcaaactg ttcgtgataa tgcacaaaca 5280ttaaacactg caatgaaagg tctacgagat
agcattgcga atgaagcaac gattaaagca 5340ggtcaaaact acacagatgc aagtcaaaac
aaacaaaatg actacaacaa tgcagtcact 5400gcagcaaaag caatcattgg tcaaacaact
agtccatcaa tgattgcgca agaaattaat 5460caagcgaaag accaagtgac agctaaacaa
caagcgttaa acggtcaaga aaacttaaga 5520actgcgcaaa caaatgcgaa gcaacatttg
aatggcttaa gtgacttaac taatgcacaa 5580aaagatgcag cgaaacgcca aatcgaaggt
gcaacgcatg ttaatgaagt aacacaagcg 5640caaaataatg cggacgcatt aaatacagct
atgacgaact tgaaaaatgg tattcaagat 5700caaaatacga ttaagcaagg tgttaacttc
actgatgcag atgaagcgaa acgtaatgca 5760tatacaaatg cagtgacgca agctgaacaa
attttaaata aagcacaagg tccaaatact 5820gcaaaagacg gtgtcgaaac tgcgttacaa
aatgtacaac gtgctaaaaa cgaattgaac 5880ggtaatcaaa atgttgcgaa cgctaagaca
actgcgaaaa atgcattgaa taaccttaca 5940tcaattaata atgcacaaaa agcagcattg
aaatcacaaa ttgaaggtgc gacaacagtt 6000gcaggtgtaa atcaagtgtc tacaatggca
tctgaattaa atactgcaat gagcaactta 6060caacgtggta ttaatgacga agcagctaca
aaagcagctc agaaatatac tgaagcagat 6120agagataaac aaactgcata caatgatgct
gtaacagcag ctaaaacgtt attagataaa 6180acagctggtt caaatgacaa taaagtagcc
gttgaacaag cattacaacg tgtgaatact 6240gctaaaacag cattaaatgg tgacgcgcga
ttaaatgaag cgaagaacac agctaaacaa 6300caattagcga caatgtcaca tttaactaat
gctcaaaaag caaacttaac agaacaaatt 6360gaacgtggta caactgttgc tggtgttcaa
ggcatccaag caaatgctgg tactttaaat 6420caagcaatga atcaattaag acaaagtatt
gcttctaaag atgcgactaa atcaagcgaa 6480gattatcaag acgcgaatgc agatttacaa
aatgcataca atgatgcggt aactaatgct 6540gaaggtatta ttagtgcaac gaataaccct
gaaatgaatc ctgatacaat taaccaaaaa 6600gcgagccaag tgaacagtgc gaagtctgca
ttgaacggtg atgaaaaatt agcagcagta 6660aaacaaactg cgaaatcaga tatcggtcgt
ttgacagact tgaacaatgc acaacgaact 6720gcggcaaatg ctgaagtgga tcaagcacca
aatcttgcag ctgtcacagc ggctaaaaat 6780aaagcaacat cgttaaacac agcgatgggt
aatttgaaac atgcacttgc tgaaaaggat 6840aatacgaaac gtagtgtcaa ttacacagat
gcggatcaac caaaacaaca agcgtatgat 6900actgcagtta cacaagcaga agcaattact
aatgcaaatg gcagtaacgc gaatgaaaca 6960caagttcaag cagcgcttaa ccaattgaat
caagctaaaa acgacttgaa tggtgataat 7020aaagttgctc aagcgaaaga aacagcaaaa
cgtgcattag cttcatatag taacttgaat 7080aacgcgcaat caactgcagc aactagtcaa
attgacaatg caacgacagt agcagacgta 7140actgctgcac aaaatactgc taatgaatta
aatacagcaa tgggtcaact tcaaaatggt 7200attaatgacc aaaacactgt taaacaacaa
gtgaacttta cagatgctga ccaaggtaag 7260aaagatgctt acacaaatgc tgttacgaat
gctcaaggta ttttagataa agcaaacggt 7320caaaatatga caaaagcaca agttgaagct
gcattaaatc aagtaacgac tgctaagaat 7380gctttaaacg gtgatgcaaa tgtaagacaa
gcaaaatcag atgcgaaagc aaacttaggt 7440acattaacac acttaaataa tgcacaaaaa
caagatttaa catcacaaat cgaaggtgca 7500acaacagtca acggtgtaaa tagtgttaaa
acgaaagcac aagacttaga tggtgcaatg 7560caacgattag agtcagcaat cgcaaataaa
gatcaaacta aagcgagcga aaactacatt 7620gacgcagatc caactaagaa aacagcattt
gataatgcca tcacacaagc tgaatcttac 7680ttaaataaag atcatggtac gaataaagat
aagcaagctg ttgaacaagc aattcaaagt 7740gtaacgtcta ctgaaaatgc tttgaacggt
gacgcgaact tacaatgcgc taaaactgaa 7800gctacacaag ctatcgataa cttgacacaa
ttgaatacac cgcaaaaaac agcattgaaa 7860caacaagtga atgctgcaca acgcgtatca
ggtgtaactg atctgaaaaa tagtgctaca 7920tcacttaata atgcgatgga tcaattaaaa
caagcaattg gtgatcatga cacaattgta 7980gctggtggta attacactaa cgcaagtcct
gataaacaag gtgcttacac tgatgcatat 8040aatgctgcga agaatatcgt aaatggttca
cctaatgtga ttacaaatgc agcagatgtt 8100actgcggcaa cacaacgtgt caataatgct
gaaacaagtt taaatggtga tacaaactta 8160gcaactgcga agcaacaagc taaagatgca
ttacgtcaaa tgacacattt atctgatgca 8220caaaaacaaa gtattactgg tcaaattgat
agcgcgacac aagtaactgg tgtacaaagt 8280gtgaaagaca atgcaacaaa tcttgacaat
gcaatgaatc aacttcgaaa tagtattgcg 8340aataaagatg aagtaaaagc gagtcaacca
tatgttgatg cagatacaga taaacaaaat 8400gcatacaata cagcagttac aagtgctgaa
aatatcatta atgcaacgag tcagccaaca 8460cttgatccat ctgcagtaac acaagcagct
aatcaagtga acactaacaa aactgcgctt 8520aatggtgcgc aaaacttagc aaataaaaag
caagaaacaa ctgctaacat caaccgatta 8580agtcatttaa acaatgctca aaagcaagat
ttaaatacac aagtgacaaa tgcaccaaat 8640attagcacag taaatcaagt gaaaactaaa
gctgaacaat tagatcaagc aatggaacgt 8700ttaatcaacg gaatccaaga caaagatcaa
gtgaaacaaa gtgttaactt tacagatgca 8760gatccagaaa aacaaacagc atacaacaat
gcggtaactg ctgctgaaaa tattattaat 8820caagcaaatg gtacaaatgc gaaccaatca
caagttgaag cagcactttc aactgtaaca 8880actactaaac aagcgttgaa tggtgataga
aaagtaacag atgctaaaaa caatgcaaac 8940caaacattat ctacgttaga taacttaaac
aatgcacaaa aaggtgctgt tactggaaac 9000atcaatcaag cgcacactgt agctgaagta
acgcaagcca ttcaaaccgc tcaggaactg 9060aatacagcga tgggtaactt gaaaaatagc
ttgaatgata aagacactac acttggcagt 9120caaaactttg cagatgcaga tccagagaag
aaaaatgcat acaatgaagc ggttcgtaat 9180gctgaaaata ttttaaataa atctacaggt
acgaacgtgc ctaaagatca agttgaagca 9240gctatgaatc aagtgaatac tacaaaagca
gcgcttaatg gtactcaaaa ccttgaaaaa 9300gcgaaacaac acgcaaatac agcaattgac
ggtttaagcc atttaacaaa tgcacaaaaa 9360gaggcattaa aacaattggt acaacaatcg
actactgttg cagaagcaca aggtaatgaa 9420caaaaagcaa acaatgttga tgcagcaatg
gacaaattac gtcaaagtat tgcagataat 9480gcgacaacaa aacaaaacca aaattatact
gatgcaagtc cgaataaaaa ggatgcgtac 9540aataatgctg tcacaactgc acaaggtatt
attgatcaaa ctacaaaccc ttcattagat 9600ccgactgtta tcaatcaagc tgctggacaa
gtaagcacgt ctaaaaatgc tttaaatggt 9660aatgaaaact tagaggcagc gaagcaacaa
gcaacgcaat ctttaggttc attagacaac 9720ttaaataatg cgcaaaaaca agctgttact
aatcaaatta atggcgcgca tactgttgat 9780gaagcaaatc aaattaagca aaatgcgcaa
aacttaaata ctgcgatggg taacttgaaa 9840caagcgatag ctgataaaga tgctacgaaa
gcaacagtta acttcactga tgcagatcaa 9900gcaaaacaac aagcatataa cactgcagtt
acaaatgctg aaaatatcat ttcaaaagct 9960aatggtggta atgcaacaca aactgaagtt
gaacaagcaa tccaacaagt aaatgcagca 10020aaacaagcat taaatggtaa tgccaacgtt
caacatgcaa aagacgaagc aacagcatta 10080attaataact ctaatgatct taaccaagca
cagaaagatg cattaaaaca acaagtacaa 10140aatgcaacta ctgtagctgg tgtaaacaat
gttaaacaaa cggcgcaaga gttaaacaat 10200gcgatgacac aattaaaaca aggcattgca
gataaagaac aaacaaaagc tgatggtaac 10260tttgtcaatg cagattctga caagcaaaat
gcatataatc aagcagtagc gaaagctgaa 10320gcattaatta gtggtacgcc tgatgttgtc
gttacaccta gcgaaattac tgcagcgtta 10380aataaagtta cgcaagctaa aaatgattta
aatggtaata caaacttagc aacggcgaaa 10440caaaatgttc aacatgctat tgatcaattg
ccaaacttaa accaagcgca acgtgatgaa 10500tacagcaaac aaatcacgca agcaacactt
gtaccaaacg tcaatgctat tcaacaagcg 10560gcaacaacgc ttaatgacgc gatgacacaa
ttgaaacaag gtattgcgaa taaagcacaa 10620attaaaggta gcgagaacta tcacgatgct
gatactgaca agcaaacagc atatgataat 10680gcagtaacaa aagcagaaga attgttaaaa
caaacaacaa atccaacaat ggatccaaat 10740acaattcaac aagcattaac taaagtgaat
gacacaaatc aagcacttaa cggtaatcaa 10800aaattagctg atgccaaaca agatgctaag
acaacacttg gtacactaga tcatttaaat 10860gatgctcaaa aacaagcgct aacaactcaa
gttgaacaag caccagatat tgcaacagtt 10920aataatgtta agcaaaatgc tcaaaatctg
aataatgcta tgactaactt aaacaatgca 10980ttacaagata aaactgagac attaaatagc
attaacttta ctgatgcaga tcaagctaag 11040aaagatgatt atactaatgc ggtttcacat
gcagaaggta ttttatctaa agcaaatggc 11100agcaatgcaa gtcaaactga agtggaacaa
gcgatgcaac gtgtgaacga agcgaaacaa 11160gcattgaatg gtaatgacaa tgtacaacgt
gcaaaagatg cagcgaaaca agtaattaca 11220aatgcaaatg atttaaatca agcgcaaaaa
gatgcattaa aacaacaagt cgatgctgcg 11280caaactgttg caaatgtaaa cacgattaag
caaacagcac aagatttaaa tcaagcaatg 11340acacaattga aacaaggtat tgcagataaa
gaccaaacta aagcaaatgg taactttgtc 11400aatgctgata ctgataagca aaatgcatat
aacaatgcgg tagcgcatgc tgaacaaatc 11460attagtggta caccaaatgc aaacgtggat
ccacaacaag tggctcaagc gttacaacaa 11520gtgaatcaag ctaagggtga tttaaacggt
aaccacaact tacaagttgc taaagacaat 11580gcaaatacag ccattgatca gttaccaaac
ttaaatcaac cacaaaaaac agcattaaaa 11640gaccaagtgt cgcatgcaga acttgttaca
ggtgttaatg ctattaagca aaatgctgat 11700gcgttaaata atgcaatggg tacgttgaaa
caacaaattc aagcgaatag tcaagtacca 11760caatcagttg actttacaca agcggatcaa
gacaaacaac aagcttataa caatgcagct 11820aaccaagcgc aacaaatcgc aaatggcaca
ccaacacctg tattggcgcc tgatacagta 11880acaaaagcag ttacaactat gaatcaagcg
aaagatgcat taaacggtga tgaaaaatta 11940gcgcaagcga aacaagatgc tttagcaaat
cttgatacgt tacgtgactt aaatcaacca 12000caacgtgatg cattacgaaa ccaaatcaat
caagcacaag ctttagctac agttgaacaa 12060actaaacaaa atgcacaaaa tgtgaataca
gcaatgggta acttgaaaca aggtattgca 12120aataaagata ctgtgaaagc aagtgagaac
taccacgatg ctgatgtcga taagcaaaca 12180gcatatacaa atgcagtgtc tcaagcggaa
ggtattatca atcaaacgac aaatccaacg 12240cttaacccag atgacattac tcgtgcatta
actcaagtga ctgatgctaa aaatagctta 12300aacggtgaag ctaaattagc cactgaaaag
caaaatgcta aagatgccgt aagtggaatg 12360acgcatttaa acgatgctca aaaacaagca
ttaaaaggtc aaatcgatca atcgcctgaa 12420attgctacag tgaaccaagt taaacaaaca
gcaacgagcc tagatcaagc aatggatcaa 12480ttatcacaag ctattaatga taaagatcaa
atattagcgg acggtaatta cttaaatgca 12540gatcctgaca aacaaaatgc gtataaacag
gcagtagcaa aagctgaagc attattgaat 12600aaacaaagtg gtactaatga agtacaagca
caagttgaaa gcatcactaa tgaagtgaac 12660gcagcgaaac aagcattaaa tggtaatgac
aatttggcaa atgcaaaaca acaagcaaaa 12720caacaattgg cgaacttaac acacttaaat
gatgcacaaa aacaatcatt tgaaagtcaa 12780attacacaag cgccacttgt tacagatgtc
actacgatta atcaaaaagc acaaacgtta 12840gatcatgcga tggaattatt aagaaatagt
gttgcggata atcaaacgac attagcgtct 12900gaagattatc atgatgcaac tgcgcaaaga
caaaatgact ataacaaagc tgtaacagct 12960gctaataata tcattaatca aactacatcg
cctacgatga atccagatga tgttaatggt 13020gcaacgacac aagtgaataa tacgaaagtt
gcattagatg gtgatgaaaa ccttgcagca 13080gctaaacaac aagcaaacaa cagacttgat
caattagatc atttgaataa tgcgcaaaag 13140caacagttac aatcacaaat tacgcaatca
tctgatattg ctgcagttaa tggtcacaaa 13200caaacagcag aatctttaaa tactgcgatg
ggtaacttaa ttaatgcgat tgcagatcat 13260caagccgttg aacaacgtgg taacttcatc
aatgctgata ctgataaaca aactgcttat 13320aatacagcgg taaatgaagc agcagcaatg
attaacaaac aaactggtca aaatgcgaac 13380caaacagaag tagaacaagc tattactaaa
gttcaaacaa cacttcaagc gttaaatgga 13440gatcataatt tacaagttgc taaaacaaat
gcgacgcaag caattgatgt tttaacaagc 13500ttaaatgatc ctcaaaaaac agcattaaaa
gaccaagtta cagctgcaac tttagtaact 13560gcagttcatc aaattgaaca aaatgcgaat
acgcttaacc aagcaatgca tggtttaaga 13620cagagcattc aagataacgc agcaactaaa
gcaaatagca aatatatcaa cgaagatcaa 13680ccagagcaac aaaactatga tcaagctgtt
caagccgcaa ataatattat caatgaacaa 13740actgcaacat tagataataa tgcgattaat
caagtagcgg caactgtgaa tacaacgaaa 13800gcagcattac atggtgatgt gaaattacaa
aatgataaag atcatgctaa acaaacggtt 13860agccaattag cacatctaaa caatgcacaa
aaacatatgg aagatacgtt aattgatagt 13920gaaacaacta gaacagcagt taagcaagat
ttgactgaag tacaagcatt agatcaactt 13980atggatgcat tacaacaaag tattgctgac
aaagatgcaa cacgtgcgag cagtgcatat 14040gtcaatgcag aaccgaataa aaaacaagcc
tatgatgaag cagttcaaaa tgctgagtct 14100atcattgcag gattaaataa tccaactatc
aataaaggta atgtatcaag tgcgactcaa 14160gcagtaatat catctaaaaa tgcattagat
ggtgttgaac gattagctca agataagcaa 14220actgctggaa attctctaaa tcatttagat
caattaacac cagctcaaca acaagcgcta 14280gaaaatcaaa ttaataatgc aacaacttgt
gataaagtgg ctgaaatcat tgcacaagcg 14340caagcattaa atgaagcgat gaaagcatta
aaagaaagta ttaaggatca accacaaact 14400gaagcaagta gtaaatttat taacgaggat
caagcgcaaa aagatgcata tacgcaagca 14460gtacaacacg cgaaagattt gattaacaaa
acaactgatc ctacattagc taaatcaatc 14520attgatcaag cgacacaggc agtgactgat
gctaaaaaca atttacatgg tgatcaaaaa 14580ctagctcaag ataagcaacg tgcaacagaa
acgttaaata acttgtctaa cttgaataca 14640ccacaacgtc aagcacttga aaatcaaatc
aataatgcag caactcgtgg tgaagtagca 14700caaaaattaa ctgaagcaca agcacttaac
caagcaatgg aagctttacg taatagcatt 14760caagatcaac aacaaacaga atctggtagc
aagtttatta atgaagataa accgcaaaaa 14820gatgcttacc aagcagcagt tcaaaatgca
aaagatttaa ttaaccaaac aggtaatcca 14880acgcttgata aagcacaagt tgaacaattg
acacatgctt ttaaacaagc taaagataac 14940ctacacggtg atcaaaaact tgcagacgat
aaacaacatg cggttactga tttaaatcaa 15000ttaaatggtt tgaataatcc gcaacgtcaa
gcacttgaaa gccaaataaa caacgcagca 15060actcgtggcg aagtagcgca aaaattagct
gaagcaaaag cgcttgatca agcaatgcaa 15120gcattacgaa atagtattca agatcaacaa
caaacggaag cgggtagcaa gtttatcaat 15180gaagataaac cgcaaaaaga tgcttaccaa
gcagcagttc aaaatgcaaa agatttaatt 15240aaccaaacag gtaatccaac actcgacaaa
tcacaagtag aacaattaac acaagcagta 15300acaactgcaa aagataatct acatggtgat
caaaaacttg ctcgtgatca acaacaagca 15360gtaacaactg taaatgcatt gccaaactta
aatcatgcac aacaacaaac attaactgat 15420gctataaatg cagcgcctac aagaacagag
gttgcacaac atgttcaaac tgctactgaa 15480cttgatcacg cgatggaaac attgaaaaat
aaagttgatc aagtgaatac agataaggct 15540caaccaaatt acactgaagc gtcaactgat
aaaaaagaag cagtagatca agcgttacaa 15600gctgcacaaa gcattacaga tccaactaat
ggttcaaatg cgaataaaga cgctgtagaa 15660caagcattaa ctaagcttca agaaaaagtg
aatgagttaa atggtaatga gagagtcgct 15720gaagctaaaa cacaagcgaa acaaactatt
gaccaattaa cacatttaaa tgctgatcaa 15780attgcaactg ctaaacaaaa tattgatcaa
gcgacgaaac ttcaaccaat cgctgaatta 15840gtagatcaag caacgcaatt gaaccaatca
atggatcaat tacaacaagc agttaatgaa 15900catgctaacg ttgagcaaac tatagattac
acacaagcag attcagataa gcaaaaggct 15960tataaacaag cgattgctga tgctgaaaat
gtattgaaac aaaatgcgaa taagcaacaa 16020gtggatcaag cacttcaaaa tattttaaat
gcaaaacaag cattaaatgg tgatgaacgt 16080gtagcacttg ctaaaacaaa tggtaaacat
gacatcgacc aattgaatgc attaaacaat 16140gctcaacaag atggatttaa aggtcgcatc
gatcaatcaa acgatttaaa tcaaatccaa 16200caaattgtag atgaggctaa ggcacttaat
cgtgcaatgg atcaattgtc acaagaaatc 16260actggcaatg aaggacgcac gaaaggtagc
acgaactatg tcaatgcaga tacacaagtc 16320aaacaagtat atgatgaagc ggttgataaa
gcgaaacaag cacttgataa atcgtctggg 16380caaaacttaa ctgcagaaca agttatcaaa
ttaaatgatg cagtcactgc agctaagaaa 16440gcattaaatg gtgaagaaag acttaataat
cgtaaagctg aagcattaca aagattggat 16500caattaacac atctaaacaa tgctcaaaga
caattagcaa tccaacaaat taataatgct 16560gaaacgctaa ataaagcatc tcgagcaatt
aatagagcaa ctaaattaga taatgcaatg 16620ggtgcagtac aacaatatat tgacgaacag
caccttggtg ttatcagcag cacaaattac 16680atcaatgcag atgacaattt gaaagcaaat
tatgataatg caattgcgaa tgcagcacat 16740gagttagata aagtgcaagg taatgcaatt
gcaaaagctg aagcagagca attgaaacaa 16800aatattatcg atgctcaaaa tgcattaaat
ggagaccaaa accttgcaaa tgccaaagat 16860aaagcaaatg cgtttgttaa ttcgttaaat
ggattaaatc aacagcaaca agatcttgca 16920cataaagcaa ttaacaatgc cgatactgta
tcagatgtaa cagatattgt taataatcaa 16980attgacttaa atgatgcaat ggaaacattg
aaacatttag ttgacaatga aattccaaat 17040gcagagcaaa ctgtcaatta ccaaaacgct
gacgataatg ctaaaacaaa cttcgatgat 17100gccaaacgtc tagcaaatac attgctaaat
agtgataaca caaatgtgaa tgatatcaat 17160ggcgcaatcc aagcagtcaa tgatgcaatc
cataatctta atggtgatca acgactacaa 17220gatgctaaag acaaggcaat tcaatcaatt
aatcaagctt tagctaataa gctaaaagaa 17280atcgaagctt caaatgcgac ggatcaagac
aagcttattg cgaaaaataa agcagaagaa 17340ttggcaaaca gcatcatcaa caacattaat
aaagcaacaa gtaatcaggc tgtatctcaa 17400gttcaaacag caggcaacca cgcgattgaa
caagtgcatg ctaatgaaat accaaaagca 17460aaaattgatg ccaataaaga cgttgataag
caagttcaag cattaattga cgaaattgat 17520cgaaatccaa atctaacaga taaggaaaaa
caagcactta aagatcgtat taatcaaata 17580cttcaacaag gtcataacga cattaacaat
gcgctgacta aagaagaaat tgaacaagct 17640aaagcacaac ttgcgcaagc attacaagac
atcaaagatt tagtgaaagc taaagaagat 17700gcgaaacaag atgttgataa acaagttcaa
gcattaattg acgaaatcga tcaaaatcca 17760aatctaacag ataaggaaaa acaagcactt
aaagatcgta ttaatcaaat acttcaacaa 17820ggtcataacg gcattaacaa tgcgatgact
aaagaagaaa ttgaacaagc caaagcacaa 17880cttgcacaag cattaaaaga aattaaagat
ttagtgaaag ctaaagaaaa tgcgaaacaa 17940gatgttgata aacaagttca agcattaatt
gacgaaatcg atcaaaatcc aaatctaaca 18000gataaggaaa aacaagcgct taaagatcga
atcaatcaaa tactgcaaca aggtcataac 18060gacattaaca atgcgatgac taaagaagaa
attgaacaag ccaaagcaca acttgcacaa 18120gcattacaag acatcaaaga tttagtgaaa
gctaaagaag atgcgaaaaa tgcaataaaa 18180gccttagcta atgcgaagcg tgatcaaatc
aattcaaatc cagatttaac acctgagcaa 18240aaagcaaaag cgctcaaaga aattgacgaa
gctgaaaaac gagcactaca aaacgttgag 18300aatgctcaaa ctatagatca attaaatcga
ggattaaact taggtttaga tgacattaga 18360aatacacatg tatgggaggt tgatgaacaa
cctgctgtaa atgaaatttt tgaagcaaca 18420cctgagcaaa tcctagttaa tggtgaactc
attgtacatc gtgatgacat cattacagaa 18480caagatattc ttgcacacat aaacttaatt
gatcagcttt cagcagaagt tattgataca 18540ccatcaactg caacgatttc tgatagctta
acagcaaaag ttgaagttac attgcttgat 18600ggatcaaaag tgattgttaa tgttcctgta
aaagttgtag aaaaagaatt gtcagtagtc 18660aaacaacagg caattgaatc aatcgaaaat
gcggcacaac aaaagattga tgaaatcaat 18720aatagtgtga cattaacact ggaacaaaaa
gaagctgcaa ttgcagaagt taataagctt 18780aaacaacaag caattgatca tgttaacaat
gcacctgatg ttcattcagt tgaagaaatt 18840caacaacaag aacaagcgta tattgaacaa
tttaatccag aacaatttac gattgaacaa 18900gcaaaatcaa atgcaattaa atcgattgaa
gatgcaattc aacatatgat tgatgaaatc 18960aaagctcgta ctgatctaac agataaagag
aagcaagaag ctattgctaa gttaaatcaa 19020ttaaaagaac aagcaattca agcgattcaa
cgtgcgcaaa gcatcagtga aataactgag 19080caattggaac aatttaaagc tcaaatgaaa
gcagctaatc caacagcaaa agaactagct 19140aaacgcaagc aagaagctat tagtagaatt
aaagactttt caaatgaaaa aataaatagt 19200attcgaaata gtgaaattgg cacagctgat
gaaaaacaag cagcaatgaa tcaaattaac 19260gaaattgtgc ttgaaacaat tagagatatt
aataatgcgc atacattaca gcaagttgag 19320gctgcattga acaatggtat tgctcgaatt
tcagcagtac aaattgtaat atctgatcgt 19380gctaaacaat cgtcaagtac tggaaatgaa
tctaatagcc atttaacaat tggttatgga 19440actgcaaatc atccatttaa cagttcgact
attggacata aaaagaaact tgatgaagat 19500gatgacattg atccacttca tatgcgtcac
tttagtaata atttcggtaa tgttattaaa 19560aacgctattg gtgtggtggg tatctctggc
ttactagcta gtttctggtt cttcattgcc 19620aaacgtcgtc gtaaagaaga tgaagaggaa
gaattagaaa taagagataa taataaagat 19680tcaataaaag agactttaga cgatacaaaa
catttaccac ttttatttgc gaaacgtcgc 19740agaaaagaag atgaagaaga tgttactgtt
gaagaaaaag attcgctaaa taatggcgag 19800tcactcgata aagttaaaca tacgccgttc
ttcttaccaa aacgtcgtcg taaagaagat 19860gaagaagatg tggaagttac aaatgaaaac
acagatgaaa aagtgttgaa agataacgaa 19920cattcaccac tcttattcgc aaaacgacgc
aaagataaag aggaagatgt tgaaacaaca 19980actagtattg aatctaaaga tgaggacgtt
cctttattat tggctaaaaa gaaaaatcaa 20040aaagataacc aatccaaaga caaaaagtca
gcatcaaaaa atacttctaa aaaggtagca 20100gctaaaaaga agaaaaagaa atctaagaaa
aataaaaaa 20139472103DNAStaphylococcus sp.
47ttgaataatc gtgataaatt acaaaaattt agtattcgaa aatacgcaat tggaacattt
60tctactgtga ttgcaacact tgtgttcatg ggtatcaata caaaccatgc aagtgccgac
120gagttgaatc aaaatcaaaa gttaattaaa caattaaatc aaacagatga tgatgattcg
180aatacgcata gtcaagaaat cgaaaataac aaacaaaatt ctagtgggca gactgaatca
240ttacgttcat caactagtca aaatcaagca aatgcacgac tgtcggatca attcaaagac
300actaatgaaa catcgcaaca attacctaca aatgtttcgg atgatagtat caatcaatcg
360catagtgaag caaatatgaa taacgaacca ttgaaagttg ataatagtac tatgcaagca
420catagtaaaa tagtaagcga tagcgatggg aatgcttctg aaaataaaca tcataaacta
480acagaaaatg tacttgcaga aagccgagca agtaaaaatg acaaagagaa agagaatcta
540caagagaaag ataaatcgca gcaagtacat ccaccattag ataaaaatgc attacaagct
600ttttttgacg catcatatca caattacaga atgattgata gagatcgtgc ggatgcaaca
660gaatatcaaa aagtcaaatc tacttttgac tacgtcaatg acttactagg taataatcaa
720aatattcctt cagaacagct tgtttcggca tatcaacaat tagagaaagc attagaactt
780gcacgtacgt taccacaaca atctactaca gaaaaacgtg gtagaagaag tacgagaagt
840gttgttgaga atcgttcatc aagaagcgat tacttagatg ctagaactga atattatgtt
900tcaaaagacg atgatgattc tggtttccct cctggtactt tcttccatgc ttcaaataga
960agatggcctt ataatttacc aagatctagg aacatcttac gtgcttctga tgtacaaggt
1020aatgcttata tcactacaaa acgacttaaa gatggatatc aatgggatat tttatttaat
1080agtaatcata aagggcatga atatatgtac tattggtttg gacttccaag tgatcaaaca
1140ccaactggtc cagtaacttt cactattatc aaccgtgatg gttcaagtac atctactggt
1200ggcgttggat ttggatcagg tgcaccacta cctcaatttt ggagatcagc aggtgctatt
1260aattctagcg tagcgaatga ttttaaacat ggctccgcta caaattatgc attttatgat
1320ggtgttaata atttttctga ctttgctaga gggggagaat tatacttcga cagagaaggc
1380gctacacaaa ctaataaata ttatggcgat gaaaacttcg cattgctaaa tagtgagaaa
1440ccagatcaaa taagaggatt agatacaata tatagtttta aaggtagtgg tgatgtaagt
1500tatcgtattt catttaaaac tcaaggagct ccaactgcaa gattgtatta tgctgctggc
1560gcgcgttctg gtgaatataa acaagcaacg aactataacc aactctatgt cgaaccttat
1620aagaattatc gaaatcgagt acagtcaaat gtccaagtta aaaatcgtac acttcattta
1680aaaagaacaa tcagacaatt cgatcctaca ttacagagaa ctactgatgt tcctattttg
1740gatagtgacg gttccggaag tattgattcg gtatacgacc cattaagtta tgtaaagaat
1800gtgactggta cagtcctagg tatttatcca tcttatcttc cttataatca ggaaagatgg
1860cagggagcta atgcaatgaa tgcctatcaa attgaagaac ttttttcaca agaaaatctt
1920caaaatgcag cacgttcagg ccgtccaatt caatttcttg taggttttga tgttgaagat
1980agccatcata accctgaaac tcttttacca gtaaatttat atgtaaaacc tgagttaaaa
2040catacaattg agttatatca cgataatgaa aaacaagata gaaaggaatt ttcagtatcg
2100aaa
21034828317DNAStaphylococcus sp. 48atgagtggaa cgcttcataa cactgtagga
tcaggaatat taccttatca acaagagata 60cgtatcaaac ttactagtaa tgaaccaatt
aaagatagtg aatggtctat tacaggatat 120cctaacacgc ttacattaca aaacgctgtg
ggtagaacaa ataatgctac tgaaaaaaac 180ttagctcttg ttggtcatat tgatccagga
aattatttca tcactgttaa gtttggtgat 240aaagtagaac aatttgaaat tagatcaaaa
ccaactccac caagaatcat tacaactgct 300aatgaattac gtggaaatcc taaccataag
cctgaaataa gagtaacaga tataccaaat 360gatactactg ctaaaatcaa acttgtgatg
ggcggaaccg atggcgatca tgatccagaa 420ataaatccat atactgtccc tgaaaactac
acagtagttg cagaagcata ccatgataat 480gatccaagta aaaatggggt cttaacattc
cgttcatcag actaccttaa agatctacca 540ttaagcggtg aattaaaggc aattgtttat
tacaatcaat atgtacaatc aaactttagt 600aaaagcgttc cgtttagtag cgatacaaca
ccacctacaa ttaatgaacc ggcaggacta 660gttcataagt attacagggg agatcatgta
gaaattactc ttccagtcac tgataatact 720ggcggttcag gtttaagaga tgtaaacgtc
aatttacctc aaggttggac aaaaaccttt 780acaatcaatc ctaataataa tactgagggt
acgcttaagt taattggtaa tatacctagt 840aatgaagcat ataatacgac atatcatttc
aatattactg caaccgataa ttctggaaat 900acaacaaatc cagctaaaac ctttatttta
aatgttggta agttggctga tgatttaaat 960ccagtcggat tatctagaga tcaactacaa
ttagtgacag acccttcttc attatctaat 1020tccgaacgag aagaggtaaa aagaaaaata
agtgaagcaa atgctaatat aagatcatat 1080ttattacaaa ataacccaat actcgctgga
gtaaacggcg atgttacatt ttattataga 1140gatggttctg tagatgttat tgatgctgaa
aatgtaatca catatgagcc cgaaagaaaa 1200tccattttca gtgaaaatgg taatacaaat
aaaaaagaag cagtaatcac tattgctaga 1260ggacaaaact ataccattgg tccaaactta
agaaaatatt tctcattaag taatggttcg 1320gatttaccta atagagattt cacctctata
tcagctattg gatctttacc ttcatcgagt 1380gaaattagtc gactcaatgt tggaaattat
aactatagag ttaatgctaa aaatgcttat 1440cataagactc aacaagaact taatttaaaa
cttaaaatag tagaggttaa tgcacctact 1500ggtaataatc gtgtatatag agttagtact
tataatttaa ctaatgatga aatcaataaa 1560atcaaacaag catttaaagc agctaattct
ggacttaatt taaacgataa cgatatcact 1620gtttcgaata actttgacca tagaaatgtt
agtagtgtga cagtaactat acgtaagggc 1680gatttgataa aagagttttc atcaaatctc
aataatatga atttcttacg ttgggttaat 1740ataagggatg attataccat ttcgtggact
tctagtaaga ttcaaggtag aaatacagat 1800ggtggattag aatggtcacc agatcataaa
tcacttattt ataaatatga tgcaacatta 1860ggtagacaaa taaatactaa tgacgtgtta
actttacttc aagcaacagc taaaaactca 1920aatttacgtt caaatatcaa tagtaatgaa
aaacagttag cagaacgagg gtctaatggg 1980tattctaaat ctataattag agatgatggc
gagaaatctt atttacttaa ctcaaatcct 2040attcaagtat tagacttagt agaaccagat
aatggttacg gtggacgtca agtcagtcat 2100tctaacgtta tatataatga aaaaaattct
tctatcgtaa atggtcaagt tccagaagct 2160aatggggcat ccgcttttaa tattgataaa
gttgttaaag ctaatgcggc aaataatggt 2220attatgggtg ttatctataa ggcacaatta
tacttagcac catacagtcc aaaaggttac 2280attgaaaaat taggccaaaa tttaagcaat
accaataacg tgattaatgt ttattttgtg 2340ccttctgata aagtaaatcc tagtataact
gtaggtaatt acgaccatca tacggtatat 2400tctggtgaaa catttaaaaa tactatcaat
gtaaatgata attatggatt aaatacagta 2460gcttctacaa gtgatagtgc aattactatg
accagaaaca acaacgagtt agtaggtcag 2520gctcctaatg ttactaatag cataaataaa
attgtaaaag ttaaagccac agataaaagt 2580ggaaatgaaa gtattgtttc tttcacagta
aatataaaac cattaaacga gaaatataga 2640ataacaactt catcaagtaa tcaaacacca
gtgagaatta gtaatattca aaacaatgct 2700aacctttcaa ttgaagatca aaatagagta
aaatcttcac tcagcatgac taaaatttta 2760ggtacaagaa attatgtcaa tgagtcaaat
aatgacgttc gtagtcaagt tgtaagtaaa 2820gtaaatagaa gtgggaacaa tgctacagtt
aatgttacaa ctacattttc tgatggtaca 2880actaatacaa taaccgttcc agttaaacat
gtgttattag aagttgtacc tactactaga 2940acaacagtaa gaggacaaca atttccaacc
ggcaaaggaa cttccccaaa tgatttcttt 3000agtttaagaa cgggaggtcc agttgatgcg
agaatagttt gggttaataa tcagggaccc 3060gatataaata gtaatcaaat tggtagagat
ttaacattac acgctgaaat attctttgat 3120ggtgaaacaa caccaattag aaaagatact
acttacaaac ttagtcaatc tattccaaag 3180caaatatatg aaacaactat caatggtcga
tttaattcat caggtgatgc atatccagga 3240aattttgttc aagcagtaaa tcaatattgg
ccagaacata tggacttcag atgggcccaa 3300ggatcaggca caccaagttc tcgtaatgca
ggttcattta ctaaaacagt tacggtagtt 3360tatcaaaacg gccaaactga aaacgttaat
gtactattca aagtcaaacc aaataaacct 3420gttattgata gtaatagtgt gatttcaaaa
ggacaattaa atggtcaaca aattttagtt 3480cgaaatgttc cacaaaatgc acaagtcact
ctatatcaat caaatggaac tgttattcct 3540aatacaaata caactataga ttctaatggt
atagctactg taacaattca aggcactcta 3600ccaaccggaa atattactgc taaaacctca
atgacaaata atgtaacgta cactaaacaa 3660aatagtagtg gaattgcttc aaatacaact
gaagatataa gtgttttttc agaaaacagt 3720gatcaagtaa atgttaccgc tggcatgcaa
gctaaaaatg atggtattaa aataattaaa 3780ggtacaaact ataattttaa tgacttcaat
agtttcataa gtaatatacc agcccattct 3840actcttacat ggaacgagga gcctaatagt
tggaaaaaca acatcggtac tacaacaaaa 3900actgttacag ttactctacc taatcatcaa
ggtacgagaa ctgtagatat tccaataaca 3960atctatccaa cagttacagc taagaatcca
gtaagagatc aaaaaggacg aaacttaacc 4020aatggtactg acgtttataa ttatattatt
tttgaaaata ataaccgtct tggaggaaca 4080gcttcttgga aagacaatcg tcaacctgat
aaaaacatag ccggtgtaca aaatttaatt 4140gcacttgtta attatcctgg catatctaca
ccattagaag ttcctgttaa agtgtgggta 4200tataattttg atttcactca acctatctac
aaaattcaag taggagatac attccctaaa 4260ggaacatggg caggctatta caaacatctt
gaaaatggag agggattacc aatagatggt 4320tggaaatttt attggaacca gcaaagtaca
ggaactacta gtgatcaatg gcaatcatta 4380gcatatacta gaactccttt tgttaaaact
ggtacttatg atgtcgttaa tcctagcaac 4440tggggtgttt ggcaaacatc acaatcagct
aaatttatag ttacaaatgc taaacctaat 4500caaccaacca taactcagtc taaaactggt
gatgtaacag taacacctgg tgctgtgcgt 4560aatatactaa taagtgggac aaatgattat
atccaagcat ctgcagataa gattgttatt 4620aataaaaatg gaaataaatt aactacattt
gttaaaaata atgatggtcg ttggactgtt 4680gaaactgggt cacctgacat aaatggtatc
ggaccaacaa ataacggaac tgctatatct 4740ttaagtcgat tagcagttag acctggggat
tcaatagaag caatagcgac tgaaggttcc 4800ggagaaacta taagtacttc agcaactagt
gaaatttata ttgtcaaagc tccacaacct 4860gaacaagtag caactcatac ttatgataat
ggaacattcg atatattacc tgacaattca 4920cgtaattctt taaatccaac tgaacgtgtc
gaaattaatt acactgaaaa attaaatggc 4980aatgaaacac aaaaatcatt cactattact
aaaaataaca acggcaaatg gacgataaat 5040aataaaccaa attatgtcga gttcaatcag
gataatggta aagttgtatt ttcggccaat 5100acaattaaac ctaattctca aattacaata
actcctaaag caggtcaggg taacactgaa 5160aacacaaatc ctactgtaat tcaagcacct
gcgcaacata ctttaacaat caatgaaatt 5220gttaaagaac agggtcaaaa tgtgactaat
gatgatatta ataatgcggt tcaagtgcca 5280aataaaaata gagttgcgat taaacaagga
aacgctcttc caacaaattt agctggtggt 5340agtacatcac atattccagt agttatttat
tacagtgatg gaagttctga agaagctact 5400gagactgtta gaactaaagt taataaaacc
gaattaatca atgctcgtcg tcgactagat 5460gaagaaatta gtaaagagaa caaaacacca
tcaagtatca gaaactttga tcaagctatg 5520aatcgtgctc aatcacaaat taatacagct
aaaagtgatg ctgaccaagt tataggcaca 5580gaatttgcaa cacctcaaca agtaaattca
gctttatcta aagttcaagc ggcacaaaat 5640aaaataaatg aagctaaagc attattacaa
aacaaggctg ataatagtca acttgtgaga 5700gcaaaagaac aattacaaca atcgattcaa
ccagccgctt caactgatgg tatgactcaa 5760gatagcacaa ggaactacaa caataaacgc
caagcagctg aacaagcaat acaacatgca 5820aatagcgtta taaataatgg agatgcaaca
tcccaacaaa ttaatgatgc taaaaacaca 5880gttgaacagg cacagagaga ttatgttgaa
gctaaaagca acttacgtgc tgataagtca 5940cagttacaaa gcgcttatga tacgttaaat
agagatgttt taacaaatga taaaaagcca 6000gcatctgtaa gacgctataa tgaagccatt
tcaaatatta gaaaagaatt agatacagct 6060aaagcggatg caagtagtac tttgcgaaac
accaatcctt ccgttgaaca agttagagac 6120gctttaaata aaataaatac tgttcaacct
aaagtgaatc aagcaattgc tttacttcaa 6180ccaaaagaaa ataattcaga acttgtacaa
gctaaaaaac gtttacaaga cgctgtaaat 6240gacatacctc aaacacaagg tatgacacaa
caaacaatta ataattataa tgacaaacaa 6300cgtgaagctg aaagagcact tacatctgca
caaagagtga ttgataatgg ggatgctaca 6360actcaagaaa ttacttctga aaaatctaaa
gtagagcaag caatgcaagc tttaactaat 6420gctaaaagta atctgagagc tgataagaat
gagttacaga ctgcatataa caaattaatt 6480gagaacgtat ctaccaatgg taaaaaaccg
gcgagtatac gtcaatacga aacagccaaa 6540gccagaatac aaaatcaaat taatgatgct
aaaaatgaag cggagcgaat tttaggtaat 6600gataatccac aagtatcaca agtaactcaa
gcattgaaca aaatcaaagc tattcaacca 6660aaattaacag aagctatcaa catgcttcaa
aacaaagaaa ataatacaga attagtcaat 6720gctaaaaaca gacttgaaaa tgcagtaaat
gatacagatc caacacacgg tatgactcaa 6780gaaacaatta ataattacaa cgctaaaaag
cgagaagctc aaaatgaaat acaaaaagcg 6840aacatgatta ttaataatgg agatgctact
gctcaagata tttcttctga aaaatctaaa 6900gtagagcaag tattacaagc attacaaaat
gctaagaatg acttaagagc tgataaaaga 6960gaattacaga ctgcatacaa taaacttata
caaaatgtta ataccaatgg taaaaaacca 7020tctagtattc aaaactataa gtctgcaaga
cgaaatatcg aaaaccaata taataccgct 7080aaaaatgaag cacataatgt tcttgaaaat
acaaacccta ctgtaaatgc agtagaagat 7140gctttacgta agataaatgc aattcaacca
gaggttacaa aagctattaa tatacttcaa 7200gataaagaag ataatagcga acttgttaga
gcaaaagaaa aattagatca agcgattaat 7260agtcaaccat cactaaatgg tatgactcaa
gaatctatta ataattacac aacaaaacgt 7320agagaagcac aaaatatagc aagttctgct
gacactatta ttaataatgg ggatgcatct 7380attgaacaaa taacagaaaa taaaattcga
gttgaagagg caactaatgc acttaacgaa 7440gcaaaacaac atttaacggc agatacaact
tctttaaaaa ctgaagtacg gaaattaagt 7500aggagaggcg acacaaacaa caaaaagcct
agcagtgtta gtgcttataa caatactatt 7560cattcgctac aatctgaaat tacacagact
gaaaatagag caaatactat catcaataag 7620cctattcgtt ctgttgaaga agtaaataat
gcattgcatg aagtaaacca attgaaccaa 7680cgcttaacag atacaattaa cttattacaa
cctttagcga ataaagaaag cttaaaagaa 7740gctcgtaatc gacttgaaag taaaattaat
gaaaccgttc aaacagacgg tatgactcaa 7800caatctgttg agaattataa gcaagctaaa
ataaaagctc aaaatgaatc tagtattgca 7860caaactctta ttaataatgg tgatgcatct
gatcaagaag tttctacaga aatagaaaaa 7920ttaaatcaaa agctgtctga attaacaaat
tcaatcaatc acttaacagt taataaagaa 7980cctttagaaa ctgccaaaaa tcagttacaa
gcaaatattg accaaaaacc tagcactgat 8040ggtatgacgc aacaatctgt acaaagctat
gaacgtaaac tacaagaagc caaagataaa 8100ataaactcaa ttaataatgt cttagctaac
aatccagatg ttaatgctat cagaacaaac 8160aaagttgaga cggaacaaat caataatgaa
ttaacacagg cgaaacaagg tcttactgtt 8220gataaacaac cattgattaa tgcaaaaact
gctttgcaac aaagtctaga taatcaacca 8280agtactactg gtatgactga agcaacaatt
caaaattata acgctaaacg tcaaaaagca 8340gagcaagtta tacaaaatgc aaataaaatt
attgaaaacg ctcaacctag tgtacaacaa 8400gtgtctgatg agaaatctaa ggtagagcaa
gcactcagtg aattgaacaa cgccaaatca 8460gcgcttagag ctgataaaca agaattacag
caagcatata atcagttgat tcaaccaacg 8520gatttaaata ataagaaacc agcttctatc
actgcgtaca atcaaagata tcaacaattt 8580agtaacgaat tgaacagcac taaaacaaat
acagatcgca ttttaaaaga gcaaaatcca 8640agtgtagctg atgtcaacaa tgcactaaat
aaagtaagag aagtacaaca aaaattaaac 8700gaagccagag cacttttaca aaataaagaa
gataatagtg cactagttcg agccaaagaa 8760caacttcaac aggcagttga ccaagtccct
tcaacagaag gtatgacgca acaaactaaa 8820gatgattaca attcaaaaca acaagctgct
caacaagaaa tatcaaaagc acaacaagtt 8880atcgataatg gcgatgcgac tacacaacaa
atttctaacg ccaaaacaaa tgttgaacgc 8940gctttagaag cattaaataa tgcaaaaact
ggtttaagag cagataaaga ggaacttcaa 9000aatgcatata atcaattaac tcaaaatatt
gatacgagcg gtaaaacgcc tgcaagtatc 9060aggaaataca atgaagctaa gtcacgtatt
caaactcaaa ttgattcagc taaaaatgaa 9120gcaaacagta ttttaacaaa tgacaatcct
caagtatcac aagtgactgc tgcgttaaac 9180aaaataaaag ctgttcaacc tgaattagat
aaagcgatag caatgcttaa aaataaagag 9240aataataatg cattggttca agcgaaacaa
caacttcaac aaattgttaa tgaagtagat 9300ccaacacaag gcatgacaac agatactgct
aataactata aatcaaaaaa acgtgaagct 9360gaagatgaaa tacaaaaagc tcaacaaatc
attaacaatg gcgatgccac tgagcaacaa 9420attactaacg aaacaaatag agtaaatcaa
gcgattaatg caataaacaa agccaaaaac 9480gatttacgtg ctgataagtc tcaattggaa
aatgcttata accaattaat acaaaatgtt 9540gatacaaatg gtaaaaaacc tgctagtatt
caacaatacc aagctgctcg acaagctatt 9600gagacgcaat acaataacgc taaatcagaa
gcacatcaaa ttcttgaaaa tagtaaccct 9660tcagttaatg aagtagcaca agcattacaa
aaagttgaag ctgtacaact taaagttaat 9720gacgcgattc atatacttca aaataaagag
aataatagtg cacttgtcac agctaaaaat 9780caacttcagc aatcagttaa tgatcaacca
ttaacaacag gtatgactca agattctatt 9840aataactatg aagctaagag aaatgaggct
caaagtgcta tcagaaatgc agaagctgtc 9900atcaacaatg gcgatgcaac tgcaaaacaa
atttcagacg agaaatctaa agttgaacaa 9960gcactagcac atttgaatga tgctaaacag
caattaactg cagatactac tgaattacaa 10020acagcagttc aacaattaaa cagaagaggc
gatacaaata ataaaaagcc aagaagtatc 10080aatgcatata ataaagcaat tcaatcatta
gaaacacaaa ttacttctgc taaagataat 10140gccaacgctg tgatacaaaa acctatacgt
actgttcaag aggtaaataa tgcattacaa 10200caagtaaatc agttgaatca acaattaact
gaagcaatta atcaacttca accgctatca 10260aataatgatg cattaaaagc tgcaagatta
aatttagaaa ataaaattaa tcaaactgta 10320caaactgatg gtatgacaca acaatctata
gaggcttatc aaaacgctaa acgcgtagcc 10380caaaatgaat ctaacactgc tttagcatta
attaataacg gcgatgccga tgaacaacaa 10440attacaactg aaacagaccg agtcaatcag
caaactacaa acttaactca agcaattaac 10500gggttaacag ttaataaaga accattagaa
accgctaaaa cagcgttaca aaataacatc 10560gaccaggtac ctagtacaga tggtatgact
cagcaatctg ttgcaaatta taatcaaaaa 10620ctacaaatag ctaaaaacga aattaacaca
attaataacg ttttagcgaa caatccagat 10680gttaatgcaa tcaaaacgaa taaagcagaa
gcggaacgaa tcagtaacga tttaacacaa 10740gctaagaata acttacaagt tgatactcaa
cctttagaaa aaataaaaag acaacttcaa 10800gatgaaattg atcaaggtac taacacagat
ggaatgactc aagattcagt ggataattac 10860aatgatagct taagtgcagc aattatagaa
aaaggcaaag taaataaatt acttaaacgt 10920aatccgacag tagaacaagt taaagagagc
gttgctaatg cacaacaagt catacaagat 10980ttacaaaatg ctcgaacttc acttgttcca
gacaaaactc aacttcaaga agctaaaaat 11040agattagaaa acagtattaa ccaacaaaca
gatactgacg gcatgactca agattcgctt 11100aacaattata atgataaatt agcaaaagct
agacaaaacc ttgaaaaaat atctaaagtt 11160ttaggtggtc aacctactgt agctgaaatt
agacaaaata cagatgaagc aaatgcacat 11220aaacaagcat tagacactgc acgttctcaa
cttacattaa atagagagcc atatatcaat 11280catattaata atgaaagtca tttaaataac
gcgcaaaaag ataattttaa agctcaagtt 11340aactcagcac ctaatcataa tactttagaa
acgattaaaa ataaggctga tactttaaat 11400caatctatga cagcattaag tgaaagtatt
gcagattacg aaaatcaaaa acaacaagaa 11460aattatttag atgcatctaa caataaacgt
caagactatg acaatgcagt caatgcggct 11520aaaggtattt taaaccaaac tcaaagtccg
acaatgagtg ctgatgtgat tgatcaaaaa 11580gctgaagatg ttaaacgtac gaaaactgcg
ttagatggaa atcaaagatt agaagttgct 11640aaacaacaag cacttaatca tttaaatacc
ttaaatgatt taaacgatgc tcagcgacaa 11700actttaactg atactataaa tcactctcca
aacatcaatt cagtgaatca agctaaagaa 11760aaagctaata ctgttaacac agcaatgact
caactgaaac aaactattgc taactatgac 11820gatgaattgc atgacggcaa ttacattaat
gcagataaag acaaaaaaga tgcttataat 11880aacgctgtta acaatgctaa acaactgatt
aatcaatctg atgctaatca agcacaactt 11940gatccagctg aaattaataa agttacacaa
agagtcaata cgactaaaaa tgatctaaat 12000ggtaatgaca aattggctga agctaaaaga
gatgctaata caaccattga tggtttaact 12060tatctaaatg aagctcaacg taacaaagct
aaagaaaatg taggcaaagc ttctacaaaa 12120acaaatatta cgagtcagtt acaagattac
aatcaattga atattgctat gcaagcatta 12180cgtaacagtg tgaacgacgt taacaatgtt
aaagcaaata gcaattatat aaatgaagat 12240aatggtccaa aagaagctta caatcaagcc
gttactcatg ctcaaacatt gataaatgca 12300caatctaacc ctgaaatgag ccgtgacgta
gtaaatcaaa aaacacaagc agtaaatact 12360gcccatcaga atttacatgg acaacaaaag
ttagaacaag cacaaagtag tgctaataca 12420gaaatcggta acttaccaaa cttaactaat
actcaaaaag ctaaagaaaa ggaactggta 12480aatagtaaac aaactcgtac ggaagtacaa
gaacaactta accaagctaa gtcactagat 12540agttctatgg gcacgttaaa atcattagtt
gctaaacaac ctacagtaca aaaaacaagt 12600gtttatatta acgaagatca acctgagcaa
tctgcctaca atgattccat tacaatggga 12660caaactataa ttaataaaac agctgatcca
gtacttgata aaactttagt tgataacgca 12720atcagtaaca tttcaactaa agagaatgca
ctgcatggtg aacaaaaatt aacaactgct 12780aaaacggaag caattaatgc acttaataca
ttagctgatt taaacacacc tcagaaagag 12840gctattaaaa cagctattaa cactgctcat
acaagaactg atgtaactgc agagcaaagt 12900aaggctaatc aaataaatag tgcaatgcac
acgttgagac aaaacatttc tgacaacgaa 12960tcagtaacaa acgaaagtaa ttatattaac
gctgaacccg aaaaacaaca tgcctttact 13020gaggctctaa ataatgctaa agaaatagtt
aatgaacaac aagccactct tgatgccaat 13080tcaattaacc aaaaagcaca agcgattctt
actactaaaa atgctttaga tggtgaagaa 13140caattacgtc gtgctaaaga aaatgccgat
caagaaatca atacgttaaa tcaattgact 13200gatgcgcaaa gaaatagtga aaaaggttta
gtcaacagtt ctcaaactag aacagaagtt 13260gcttctcaat tagcaaaagc taaagaacta
aataaggtga tggaacaact gaatcacctt 13320atcaatggta aaaaccaaat gataaatagc
agtaaattta tcaatgaaga tgcgaaccaa 13380caacaagcat attcaaatgc gattgcaagt
gcagaagcgc ttaaaaacaa atcacaaaac 13440cctgaattag ataaagtaac aattgaacaa
gcaattaata atattaattc tgcaattaac 13500aatctaaacg gtgaagctaa actgactaaa
gctaaagaag atgctgttgc ttcaataaac 13560aacctaagcg gattaacaaa cgagcaaaaa
acaaaagaaa atcaagccgt taatggcgct 13620caaactagag accaagttgc taataaatta
cgtgatgctg aagcattaga tcaatcaatg 13680caaacattac gtgacttagt taacaatcaa
aatgcaatac attcaacaag taattatttt 13740aacgaggatt caactcaaaa gaatacttat
gataatgcaa ttgataatgg ctcgacatat 13800ataactggtc aacacaatcc agaattaaat
aaatctacta ttgatcaaac gattagccga 13860attaacacag ctaaaaatga tttacatggt
gtagaaaagt tacaaagaga taagggaact 13920gctaatcaag aaattggaca attaggttat
ttaaatgacc ctcaaaaatc tggtgaggaa 13980tccttagtca acggttcaaa tacacgttct
gaagtagaag agcatcttaa tgaagctaaa 14040tcattaaata atgcaatgaa acaattaaga
gataaagtag ctgaaaagac taatgtcaaa 14100caaagtagcg attacattaa tgattcaact
gaacatcaac gtgggtatga tcaagcactt 14160caagaagcag aaaatattat taatgaaatc
ggtaatccaa cattaaataa atcggaaatt 14220gaacaaaagt tacaacaatt gactgacgct
caaaatgcgt tacaaggttc acatctatta 14280gaagaagcta aaaataatgc gattactgga
atcaataaac ttacagcatt aaatgatgca 14340caacgtcaaa aagcaattga aaatgttcaa
gcacagcaga caatcccagc agttaatcaa 14400caattaactt tggatagaga aataaatact
gcaatgcaag ctttacgaga taaagtaggc 14460caacaaaata acgttcacca acaaagtaat
tatttcaatg aagatgaaca accaaaacat 14520aactatgata attctgtaca agccggtcaa
actattattg ataaacttca agatccaatc 14580atgaacaaaa atgaaattga gcaggctatt
aatcaaatca atacgactca aacagcgtta 14640agtggagaaa ataaattaca cactgaccaa
gaaagcacaa atagacaaat agaaggttta 14700tctagtttga acacagctca aatcaacgcc
gaaaaagatt tagtcaatca agctaaaaca 14760agaacagatg ttgctcaaaa gttagctgca
gctaaagaaa taaattctgc tatgagtaat 14820ttaagagatg gcattcaaaa taaagaggac
atcaaacgta gcagtgcata tatcaacgca 14880gatccgacta aagttacagc ttacgatcaa
gcactacaga acgcagaaaa tatcatcaat 14940gccacaccaa acgtagagct taataaagct
acaattgaac aagcgctatc acgcgttcaa 15000caagcacaac aagatcttga tggtgttcaa
caattagcta atgctaaaca acaagctaca 15060caaactgtca atgggttaaa tagcttaaat
gacggtcaaa agcgtgaatt aaatctatta 15120attaattcag ctaatacccg tacaaaagta
caagaagaat taaacaaagc aactgaattg 15180aaccatgcga tggaagcttt aagaaacagt
gttcaaaacg ttgatcaagt aaaacaaagt 15240agcaattatg tcaatgaaga tcaacctgaa
cagcacaatt atgataatgc tgtcaatgaa 15300gctcaagcta caatcaacaa caatgctcaa
cctgttctag acaaattagc tatagaacgt 15360ttaactcaaa ctgttaacac tacaaaagat
gcattacatg gtgctcaaaa actgacacaa 15420gaccaacaag ctgctgaaac tggaatacgt
ggtttaacga gtctcaatga acctcagaaa 15480aatgctgaag tagctaaagt aactgcagca
acaacacgtg atgaagtgag aaatattcgt 15540caagaagcaa caacattaga tactgcaatg
cttggtttac gtaaaagcat taaagataaa 15600aacgatacta aaaatagtag taaatatatt
aatgaggatc atgaccaaca acaagcttat 15660gacaatgctg taaataatgc tcaacaagtt
atcgatgaaa ctcaagcaac gttaagctca 15720gatacaatca atcaattggc aaatgccgta
actcaagcta aatctaatct tcatggagat 15780actaaactac aacacgataa agatagtgct
aaacaaacga ttgctcaatt acagaatttg 15840aattcagctc aaaaacatat ggaagattct
ttaattgata atgaatctac acgtacgcaa 15900gtccaacacg atttaacaga agctcaagct
ttagatggtt taatgggtgc cttaaaagaa 15960agtattaaag attatactaa tattgtttca
aacggtaatt acatcaatgc ggaaccatct 16020aagaaacaag catatgatgc agctgtacaa
aatgctcaaa atataataaa tggaacgaat 16080caaccaacaa ttaataaagg taatgtcact
acagcaacac aaaccgtgaa aaatactaaa 16140gatgccttag acggtgatca tagattagag
gaagctaaaa ataatgccaa tcaaacaatc 16200agaaatctat ctaatttgaa caatgcccaa
aaagatgcag agaaaaatct agttaatagc 16260gcatcaacat tagaacaagt tcaacaaaac
ttacaaaccg ctcaacaatt agataatgct 16320atgggtgagt tacgacaaag tattgctaaa
aaagatcaag tgaaagcaga tagtaaatat 16380ctaaatgaag atcctcaaat taagcaaaac
tatgatgatg cagttcaacg tgttgaaact 16440attattaacg aaactcaaaa ccctgaatta
cttaaagcaa acattgacca agcaactcaa 16500tccgttcaaa atgcagaaca agctttacat
ggtgctgaaa aattaaatca agacaaacaa 16560acgtcttcga cagaactaga tggattaaca
gatttaacag atgcacaacg tgaaaaactc 16620agagaacaaa ttaacacttc taatagtaga
gatgatatta agcaaaaaat tgagcaagca 16680aaagcactaa atgacgcaat gaaaaaactt
aaagaacaag ttgcgcaaaa agatggtgtt 16740catgctaaca gtgattatac aaatgaagat
tctgcacaaa aagatgcgta taataatgca 16800cttaaacaag cggaagacat tattaataac
agctcaaatc ctaacttaaa tgcacaagac 16860attactaatg ctttaaataa tattaaacaa
gcacaagata accttcatgg agctcaaaaa 16920ttacagcaag acaaaaatac aactaatcaa
gccattggta acttaaatca tcttaatcaa 16980cctcaaaaag atgcgcttat acaagctatt
aatggagcta catctaggga ccaagttgca 17040gaaaaactta aagaggccga agcgcttgat
gaagctatga aacaacttga agatcaagtg 17100aatcaagatg atcaaatttc aaatagcagc
ccattcataa atgaagactc agacaaacaa 17160aaaacttata atgataaaat ccaagctgca
aaagaaataa ttaatcaaac atctaatcca 17220accttagata aacaaaaaat tgctgataca
cttcaaaata ttaaagatgc agtgaataat 17280ttacatggtg atcaaaaatt agctcaatct
aaacaagatg ctaataatca attaaatcat 17340ttagatgact taaccgaaga acaaaaaaac
cattttaaac cgttaattaa taatgctgat 17400actcgagatg aggtaaataa acaactagag
attgctaaac aattaaatgg tgatatgagt 17460acacttcata aagtcataaa tgataaagat
caaattcaac atttaagcaa ttacattaat 17520gctgataatg ataaaaaaca aaattatgat
aatgctatta aagaagctga ggatttaatt 17580cataatcatc cagatacatt agatcataaa
gcattacaag atttattaaa caagatagac 17640caagcgcata acgaattaaa tggagaatcc
agatttaaac aggctttaga caatgcttta 17700aacgacatag atagcttaaa cagtctcaat
gttccacaac gccaaactgt taaggataac 17760atcaaccatg tgacaactct agaaagttta
gctcaagaat tgcagaaagc aaaagagctt 17820aatgatgcta tgaaagcaat gagagatagc
attatgaatc aagagcaaat tcgtaaaaat 17880agcaattata ctaatgaaga cttagctcaa
caaaatgcct ataatcatgc agtagataaa 17940ataaataaca ttattggtga agacaatgcg
acgatggatc ctcaaataat caaacaagca 18000actcaagata taaatacagc tataaatgga
ttaaatggag atcaaaaact tcaagatgca 18060aagacagatg ctaaacaaca aattactaac
tttactggtt taactgaacc acaaaaacaa 18120gcattggaaa acatcattaa ccaacaaaca
agcagagcaa atgttgctaa acagttaagt 18180catgctaaat tcttaaatgg aaaaatggaa
gaattaaaag ttgcagtagc caaagcgtca 18240ttagtaagac aaaatagtaa ctatattaat
gaagatgtct ctgaaaaaga agcatatgaa 18300caagctatcg caaaaggtca ggaaataatt
aattcagaaa ataatccaac aataagtagt 18360actgatatca atcgtaccat tcaagaaatt
aatgatgctg aacaaaatct tcatggtgat 18420aataaattaa gacaagcaca ggaaattgca
aagaatgaaa tacaaaatct agacggatta 18480aattcagctc aaataacaaa attaatccaa
gatataggca gaacaacaac taaacctgca 18540gtaactcaga aactagaaga agcaaaagca
ataaaccaag ctatgcaaca acttaaacaa 18600agtatagccg ataaggatgc tactctaaat
tctagtaact atctcaatga agattctgag 18660aaaaagttag cgtacgataa tgctgtaagc
caagctgaac aactcataaa tcaacttaac 18720gacccaacta tggatataag taatattcaa
gctattactc aaaaggtcat tcaagcaaaa 18780gattcattgc acggtgcgaa taaacttgca
caaaatcaag cagattcaaa tttaataata 18840aatcaatcaa caaatttaaa tgataaacaa
aagcaagcat taaatgactt aattaatcat 18900gctcaaacta aacagcaagt ggcagaaata
attgcacaag ctaataagtt aaataacgaa 18960atgggcacac taaaaacact cgtagaagaa
cagtcaaacg ttcatcaaca aagtaaatat 19020attaatgaag atccgcaagt tcaaaatatt
tataatgact ccattcaaaa aggtcgagaa 19080atattaaacg gcactacaga tgatgtttta
aacaacaata aaatagcaga tgccattcaa 19140aacattcatt taactaaaaa cgatttacat
ggtgatcaaa aattacaaaa agcacaacaa 19200gatgcaacca atgaattaaa ctatttaaca
aatctaaaca attctcaaag acaaagcgag 19260catgatgaga ttaactctgc tccttcaaga
actgaagttt ctaatgattt aaatcatgct 19320aaagcactta atgaagctat gcgtcaactt
gagaatgaag ttgctcttga aaacagtgtt 19380aaaaaattaa gcgactttat caatgaagat
gaagcggcac aaaatgaata tagtaatgca 19440cttcaaaaag ctaaagacat tatcaacggc
gttccaagta gcactttaga taaagctaca 19500attgaagatg ctttattaga attgcaaaat
gctagagaaa gtttacatgg tgagcaaaaa 19560cttcaagagg ctaaaaatca agctgttgct
gaaattgata atttacaagc attaaatcct 19620ggacaggttc ttgctgaaaa aacattagtt
aaccaagcat caaccaaacc agaagttcaa 19680gaagccttac aaaaagcaaa agaacttaat
gaagctatga aagcactgaa aactgaaata 19740aataaaaaag aacaaatcaa ggctgatagt
agatatgtaa atgctgacag tggtcttcaa 19800gcaaattaca attctgcgtt aaattatggt
tctcaaatta ttgcaactac ccaaccacca 19860gagcttaata aagatgtaat aaatagagca
actcaaacga ttaaaactgc tgaaaataat 19920ttaaatgggc aatctaaatt agcagaggct
aagtcagacg gaaatcaaag catcgaacat 19980ttgcaaggat taacacaatc acaaaaagat
aaacaacatg atttaattaa tcaagctcaa 20040actaaacaac aggtagatga tatcgtaaat
aactctaaac aattagataa ctctatgaat 20100caactacaac aaattgttaa caatgacaat
acagtaaaac aaaatagtga tttcattaat 20160gaagattcca gccaacagga tgcttataat
catgcaattc aagcagcaaa agatttgata 20220actgctcatc caactatcat ggataaaaat
caaatagatc aagctattga aaatatcaaa 20280caagcactta atgatttaca cggtagtaat
aaactatcag aagataaaaa agaagcttca 20340gaacaactac aaaaccttaa tagcttgacg
aacgggcaaa aagatacgat tttaaatcat 20400attttcagtg caccaacaag aagccaagta
ggagaaaaaa ttgcaagtgc taaacaatta 20460aataatacaa tgaaagcact tagagattct
attgctgata ataatgaaat tttacaaagt 20520agtaagtact tcaatgaaga ttctgaacaa
caaaatgctt ataatcaagc cgtaaataaa 20580gctaaaaata taattaatga tcaaccaaca
ccagtaatgg caaatgatga gattcaaagt 20640gtcctaaatg aagttaaaca aactaaagat
aatttacatg gtgatcaaaa acttgctaac 20700gacaagacag atgctcaagc aacattaaat
gcgttaaatt acttaaatca agcgcaaaga 20760ggtaatcttg aaactaaagt tcaaaactct
aattctagac cagaagtaca aaaagtagtt 20820caattagcaa atcaacttaa tgatgcgatg
aaaaaattag atgatgcttt aactggtaat 20880gacgcaataa aacaaacgag taattatatt
aatgaagata cttctcaaca agttaacttt 20940gatgagtata cagatagagg taaaaacata
gttgctgaac aaacaaatcc aaatatgtct 21000ccaactaata ttaacactat tgctgataaa
attactgaag ctaaaaacga tttacatggc 21060gtacaaaaac taaaacaagc tcaacaacag
tccatcaata ctattaatca aatgactggt 21120ctaaaccaag ctcaaaaaga acaattaaat
caagaaattc aacaaactca aacccgttct 21180gaagtacatc aagtaattaa taaagcacaa
gctttaaatg attcaatgaa tactttacgt 21240caaagtatta ctgatgaaca tgaagttaaa
caaacaagta actacatcaa tgaaactgtt 21300ggtaatcaaa ctgcatataa caatgccgtt
gatcgtgtaa aacaaataat caatcaaaca 21360tctaatccaa ctatgaatcc tttagaggtg
gaacgtgcaa catcaaatgt aaaaatttct 21420aaagatgcac ttcatggtga acgtgaattg
aatgacaata aaaattcaaa aacttttgca 21480gtcaatcact tagataacct caatcaagct
caaaaagaag cattaactca tgaaattgaa 21540caagcaacta tagtttcaca agtaaataat
atctataaca aagcgaaagc tttaaataat 21600gatatgaaaa aacttaaaga tatcgttgct
caacaagata atgtgagaca atcaaacaat 21660tatataaacg aggatagtac acctcaaaat
atgtacaacg atacaattaa tcatgcacaa 21720tcaatcattg atcaagtagc aaaccctacg
atgtctcatg acgaaataga gaatgcaatc 21780aataacataa agcatgccat caatgcactc
gatggagaac ataaattaca acaagcaaaa 21840gaaaatgcaa acttattgat taatagttta
aacgatttaa atgcaccaca aagagatgcc 21900ataaatagat tggttaatga agctcaaaca
agagaaaaag tagctgaaca acttcaaagt 21960gctcaagctt taaatgacgc tatgaagcat
ttaagaaaca gcattcaaaa tcaatcatcc 22020gtaagacaag agagcaaata tattaatgca
agtgatgcta aaaaagagca atataatcac 22080gcagttagag aagtcgaaaa tattatcaat
gaacaacatc caacattgga taaagaaata 22140attaagcaac taacggatgg tgtaaatcaa
gcgaataatg acttaaatgg cgttgaatta 22200ttagatgctg ataagcaaaa cgcacatcaa
tcgataccta cattgatgca cttaaatcaa 22260gcacaacaaa acgcattaaa tgaaaaaatt
aataacgcag ttaccagaac tgaagttgcg 22320gctattattg gccaagcaaa actactcgat
catgctatgg agaatttaga agaaagtatc 22380aaagataaag agcaagtcaa acagtcaagt
aactatatta atgaagattc tgatgttcaa 22440gaaacatacg ataacgccgt tgatcatgtg
acagaaatac ttaatcaaac agtaaatcca 22500actttatcta ttgaagatat agagcatgct
atcaacgaag ttaatcaagc gaaaaaacaa 22560ctcagaggta aacaaaaact ttatcaaact
atcgatttag ctgataaaga attaagtaaa 22620ttggatgatt taacatcaca acaaagcagt
tcaatatcta atcaaatata tactgctaaa 22680acgagaacag aagttgccca agcaattgaa
aaagcaaaat cattaaatca tgcaatgaaa 22740gcacttaaca aagtatataa aaatgcagat
aaagtgttag atagtagtcg attcattaac 22800gaagatcaac ctgaaaaaaa ggcgtatcaa
caagctataa atcatgttga ttcaatcatt 22860catagacaaa caaatcctga aatggatcca
acagtaatca atagcataac tcatgaactc 22920gaaacagctc aaaataactt acatggtgat
cagaaacttg ctcatgcaca acaagatgcc 22980gctaatgtaa ttaatggtct aattcatctt
aatgttgctc aacgtgaggt aatgataaat 23040acgaatacaa atgctacaac acgcgaaaaa
gttgcaaaga acttagataa tgctcaagct 23100cttgataaag ctatggaaac actacaacaa
gtagttgctc ataaaaataa tatattgaac 23160gatagtaaat atttaaatga agattcaaaa
tatcaacaac aatacgatcg agttattgct 23220gatgccgaac aactacttaa tcagacaaca
aatccaacat tagaacctta taaagtcgat 23280attgttaagg ataatgtcct agctaacgaa
aaaatactat ttggcgcaga aaaactatca 23340tatgacaaat caaatgcaaa tgatgaaatt
aaacatatga attatcttaa taatgcacaa 23400aagcaatcta taaaagatat gatttctcac
gcagcattaa gaactgaagt taaacaactt 23460ctgcaacaag ctaaaatcct tgatgaagcc
atgaaatcac ttgaagataa aactcaagta 23520gtgattacag atactacttt gcctaattac
actgaagctt cagaggataa aaaggaaaaa 23580gtagaccaaa ctgtatcaca tgctcaagcg
attattgata aaataaatgg ctcaaatgta 23640agtttagatc aagtacgaca agcactagaa
caattaactc aagcatcaga aaacctcgat 23700ggtgatcagc gagttgaaga agctaaagtt
catgctaatc aaacaattga tcaattaaca 23760catcttaatt cattacaaca acaaactgcg
aaagaaagtg ttaaaaacgc aacaaaacta 23820gaagaaatcg ctactgttag taacaatgct
caggcattaa acaaagtaat gggtaaatta 23880gaacaattca ttaatcatgc tgattctgtt
gaaaatagtg ataattatag acaagccgac 23940gacgacaaaa tcatcgctta tgatgaagca
cttgaacatg gacaagatat acaaaaaact 24000aacgcaaccc aaaatgaaac aaaacaagcg
ttacaacaat taatatatgc agaaacatcg 24060ttaaatggtt tcgaaagatt aaatcatgct
agaccacgag ctttagaata tatcaaatca 24120ctagaaaaaa taaacaatgc tcaaaagtct
gctttagagg ataaagtaac gcaatcgcat 24180gatttattag aattagaaca tattgtcaac
gagggcacaa acctcaatga cattatgggt 24240gaattagcta acgcaatcgt taataactat
gctccaacca aagcaagtat aaattatatt 24300aacgccgata acctacgcaa agataacttt
actcaagcta tcaacaatgc acgtgatgca 24360ctcaacaaaa ctcaaggtca gaacttagat
ttcaatgcaa ttgatacatt taaagatgat 24420atattcaaaa ctaaagatgc acttaacggt
attgaacgtt taacagctgc aaaatcaaaa 24480gcagaaaaac taattgatag tttaaaattt
attaataaag ctcaattcac acatgcaaat 24540gatgaaatta tgaatactaa ttctattgca
caattgtcta gaatcgtgaa tcaagcattt 24600gatttaaatg atgcaatgaa atctttaaga
gatgaactta ataatcaagc ttttcctgtc 24660caagcaagct caaattatat aaattcagat
gaagatttaa aacaacaatt tgaccatgct 24720ttaagtaatg ctcgaaaagt tcttgcaaaa
gaaaatggta aaaatttaga tgaaaaacaa 24780attcagggac tcaaacaagt gattgaggat
actaaagatg ctttaaatgg tatccaacgt 24840ttatcaaaag ctaaagctaa agcaattcaa
tacgtacaat ctttatctta tatcaatgat 24900gcacagcgtc atattgctga aaataatatt
cacaactctg atgatttatc atctttagca 24960aatacattat ctaaagctag tgatttagat
aatgcaatga aagacttacg agatactata 25020gaaagtaatt caacttctgt tccaaatagt
gtgaattata ttaatgctga taagaattta 25080caaattgaat ttgatgaggc gctacaacaa
gcaagtgcaa caagttctaa aacttcagaa 25140aatccagcaa cgattgaaga agtattaggt
cttagtcaag ccatttacga tacaaaaaat 25200gcattaaatg gtgaacaacg acttgcaact
gagaagagca aagatctaaa attaataaaa 25260ggattaaaag atttaaataa agcacaactt
gaagatgtca caaacaaggt aaattcagca 25320aatactttaa cagagttatc tcagctcact
caatcaacgt tagaattaaa cgataaaatg 25380aaattattga gagataagct taaaacttta
gtaaatcctg ttaaagcaag tttaaattat 25440agaaacgctg attataattt aaaacgtcaa
tttaacaaag ctttaaaaga agctaaaggc 25500gtattaaata aaaatagcgg tacaaatgtc
aatatcaatg acattcaaca tcttttaaca 25560caaatagata atgctaaaga ccaattaaat
ggtgaacgac gtctaaaaga acatcaacaa 25620aaatctgaag tatttattat taaagaatta
gatatactta ataatgctca aaaagctgca 25680ataattaatc agattagagc gtctaaagac
attaaaataa ttaatcaaat cgttgataat 25740gcaatagaat taaatgatgc tatgcaaggt
ttaaaagaac atgtagctca attaacagca 25800actacaaaag acaacattga atatttaaat
gctgatgaag accataaatt acaatatgat 25860tacgctatca acttagcgaa taatgttctt
gacaaagaaa acggtacaaa taaagacgct 25920aatatcataa ttggaatgat tcaaaacatg
gatgatgcta gagcacttct aaatggaatt 25980gaaagactta aagatgctca aacaaaagca
cataatgaca ttaaagatac gctcaaacgt 26040caacttgatg aaattgaaca cgctaatgca
acatcaaatt ctaaagctca agctaaacaa 26100atggtaaatg aggaagctag aaaagcgctt
tctaatatta atgacgcaac atcaaatgat 26160ttagttaatc aagcaaaaga tgaagggcaa
tctgcaattg aacacataca tgcagatgaa 26220ttacctaaag caaaactaga tgctaatcaa
atgattgacc aaaaagttga agatataaat 26280cacttaatta gtcaaaatcc aaacttatca
aatgaagaaa aaaataaact aatatctcaa 26340attaataagt tagtaaatgg aattaagaat
gaaattcaac aagctataaa caaacaacaa 26400atagaaaatg ctacaacaaa actagatgaa
gtcattgaaa ctactaaaaa attaattatc 26460gccaaagcag aagctaaaca aatgataaaa
gagttatcac aaaagaaacg agatgcaata 26520aataacaaca ctgatttaac accttctcaa
aaggcacatg ctttagcaga tattgataaa 26580acagaaaaag atgcacttca acatatcgaa
aattctaatt caattgatga tatcaataac 26640aataaagagc atgcatttaa tactttagct
catatcatta tttgggatac tgatcagcaa 26700ccattagttt ttgaactacc tgaattgagc
cttcaaaatg ctctagtaac aagtgaggtg 26760gttgttcaca gagatgaaac tatttcatta
gaatctataa ttggagctat gactttaact 26820gatgaactta aagtcaatat tgtttcatta
ccgaacactg ataaagtagc tgatcaccta 26880accgctaaag ttaaggttat tttagctgat
ggctcatatg tcactgtaaa tgttccagtc 26940aaagttgtag aaaaagaatt acaaatagct
aaaaaggatg ctataaaaac aattgatgtt 27000ctggtaaaac aaaaaatcaa agatatagat
tctaataacg aattaacgtc tactcaacgt 27060gaagatgcaa aagctgaaat tgaaagattg
aaaaagcaag ccatcgataa agtgaatcat 27120tcaaaatcga ttaaagatat tgaaacagta
aaacgaactg attttgaaga aatagatcag 27180tttgatccta aacgctttac gctaaataaa
gctaaaaagg atatcattac tgatgttaat 27240actcaaatcc aaaatggttt caaagaaatt
gaaacaataa aaggtttaac ttctaatgaa 27300aaaactcagt ttgataaaca attaactgca
ctacaaaaag aatttttaga aaaagtcgag 27360catgctcata atttagtaga attaaatcaa
ttacaacaag agtttaataa tagatataaa 27420catattttaa accaagcaca tttactaggt
gaaaaacata tagcagaaca taaattagga 27480tatgttgtag taaacaaaac tcagcaaata
ctaaataatc aatctgcttc ttactttata 27540aaacaatggg cacttgatag aattaaacaa
attcaactag aaacgatgaa ttcaattcgt 27600ggtgcgcata ccgtacaaga tgtacacaaa
gcattattac aaggtataga gcaaatcttg 27660aaagtaaatg taagtattat aaatcaatct
ttcaacgatt ccttgcataa ctttaattat 27720cttcattcaa aatttgatgc tagattaaga
gaaaaggatg ttgcaaacca tatcgtacaa 27780actgaaacat tcaaagaagt tctaaaagga
acgggtgttg aaccaggtaa aatcaacaaa 27840gaaacacagc aaccaaaact tcataagaat
gataatgata gcctattcaa acatttagtt 27900gataatttcg gcaaaactgt aggtgttatt
acattaactg gtttactttc tagtttctgg 27960ttagttttgg ctaaaagacg taaaaaagaa
gaagaagaaa aacaatcgat aaaaaatcat 28020cacaaagata ttcgtctttc agatactgat
aaaatagatc caattgtaat aactaagcgt 28080aaaatagata aagaagaaca aattcaaaac
gatgacaaac attcaattcc agttgctaaa 28140cataagaaat ctaaagaaaa gcaattgagt
gaagaggata ttcattcaat ccccgtcgtt 28200aagcgtaaac aaaacagtga taacaaagat
acaaaacaga agaaagttac ttctaaaaag 28260aagaaaacgc ctcagtcaac taaaaaagtt
gtaaaaacca aaaagcgttc taaaaag 28317493348DNAStaphylococcus sp.
49atgagagata agaaaggacc ggtaaataaa agagtagatt ttctatcaaa taaattgaat
60aaatattcaa taagaaaatt tacagttgga acagcatcta ttttaattgg ctcactaatg
120tatttgggaa ctcaacaaga agcagaagca gctgaaaaca atattgagaa tccaactaca
180ttaaaagata atgtccaatc aaaagaagtg aagattgaag aagtaacaaa caaagacact
240gcaccacaag gtgtagaagc taaatctgaa gtaacttcaa acaaagacac aatcgaacat
300gaagcatcag taaaagctga agatatatca aaaaaggagg atacaccaaa agaagtagct
360aatgttgctg aagttcagcc gaaatcgtca gtcactcata acgcagaggc acctaaggtt
420agaaaagctc gttctgttga tgaaggctct tttgatatta caagagattc taaaaatgta
480gttgaatcta ccccaattac aattcaaggt aaagaacatt ttgaaggtta cggaagtgtt
540gatatacaaa aaaacccaac agatttaggg gtatcagagg taaccaggtt taatgttggt
600aatgaaagta atggtttgat aggagcttta caattaaaaa ataaaataga ttttagtaag
660gatttcaatt ttaaagttag agtggcaaat aaccatcaat caaataccac aggtgctgat
720ggttgggggt tcttatttag taaaggaaat gcagaagaat atttaactaa tggtggaatc
780cttggggata aaggtctggt aaattcaggc ggatttaaaa ttgatactgg atacatttat
840acaagttcca tggacaaaac tgaaaagcaa gctggacaag gttatagagg atacggagct
900tttgtgaaaa atgacagttc tggtaattca caaatggttg gagaaaatat tgataaatca
960aaaactaatt ttttaaacta tgcggacaat tcaactaata catcagatgg aaagtttcat
1020gggcaacgtt taaatgatgt catcttaact tatgttgctt caactggtaa aatgagagca
1080gaatatgctg gtaaaacttg ggagacttca ataacagatt taggtttatc taaaaatcag
1140gcatataatt tcttaattac atctagtcaa agatggggcc ttaatcaagg gataaatgca
1200aatggctgga tgagaactga cttgaaaggt tcagagttta cttttacacc agaagcgcca
1260aaaacaataa cagaattaga aaaaaaagtt gaagagattc cattcaagaa agaacgtaaa
1320tttaatccgg atttagcacc agggacagaa aaagtaacaa gagaaggaca aaaaggtgag
1380aagacaataa caacaccaac actaaaaaat ccattaactg gagaaattat tagtaaaggt
1440gaatcgaaag aagagatcac aaaagatccg attaatgaat taacagaata cggaccagaa
1500acgatagcac caggtcatcg agacgaattt gatccgaagt taccaacagg agagaaagaa
1560gaagttccag gtaaaccagg aattaagaat ccagaaacag gagacgtagt tagaccaccg
1620gtcgatagtg taacaaaata tggacctgta aaaggagact cgattgtaga aaaagaagaa
1680attccattcg agaaagaacg taaatttaat cctgatttag caccaggaac agaaaaagta
1740acaagagaag gacaaaaagg tgagaagaca ataacgacac caacactaaa aaatccatta
1800actggagaaa ttattagtaa aggtgaatcg aaagaagaga tcacaaaaga tccgattaat
1860gaattaacag aatacggacc tgaaacaata gcgccaggtc atcgagacga atttgatccg
1920aagttaccaa caggagagaa agaagaagtt ccaggtaaac caggaattaa gaatccagaa
1980acaggagacg tagttagacc gccggtcgat agcgtaacaa aatatggacc tgtaaaagga
2040gactcgattg tagaaaaaga agaaattcca ttcaagaaag aacgtaaatt taatcctgat
2100ttagcaccag ggacagaaaa agtaacaaga gaaggacaaa aaggtgagaa gacaataacg
2160acgccaacac taaaaaatcc attaactgga gaaattatta gtaaaggtga atcgaaagaa
2220gaaatcacaa aagatccgat taatgaatta acagaatacg gaccagaaac gataacacca
2280ggtcatcgag acgaatttga tccgaagtta ccaacaggag agaaagagga agttccaggt
2340aaaccaggaa ttaagaatcc agaaacagga gatgtagtta gaccaccggt cgatagcgta
2400acaaaatatg gacctgtaaa aggagactcg attgtagaaa aagaagaaat tccattcgag
2460aaagaacgta aatttaatcc tgatttagca ccagggacag aaaaagtaac aagagaagga
2520caaaaaggtg agaagacaat aacgacgcca acactaaaaa atccattaac tggagaaatt
2580attagtaaag gtgaatcgaa agaagaaatc acaaaagatc cagttaatga attaacagaa
2640ttcggtggcg agaaaatacc gcaaggtcat aaagatatct ttgatccaaa cttaccaaca
2700gatcaaacgg aaaaagtacc aggtaaacca ggaatcaaga atccagacac aggaaaagtg
2760atcgaagagc cagtggatga tgtgattaaa cacggaccaa aaacgggtac accagaaaca
2820aaaacagtag agataccgtt tgaaacaaaa cgtgagttta atccaaaatt acaacctggt
2880gaagagcgag tgaaacaaga aggacaacca ggaagtaaga caatcacaac accaatcaca
2940gtgaacccat taacaggtga aaaagttggc gagggtcaac caacagaaga gatcacaaaa
3000caaccagtag ataagattgt agagttcggt ggagagaaac caaaagatcc aaaaggacct
3060gaaaacccag agaagccgag cagaccaact catccaagtg gcccagtaaa tcctaacaat
3120ccaggattat cgaaagacag agcaaaacca aatggcccag ttcattcaat ggataaaaat
3180gataaagtta aaaaatctaa aattgctaaa gaatcagtag ctaatcaaga gaaaaaacga
3240gcagaattac caaaaacagg tttagaaagc acgcaaaaag gtttgatctt tagtagtata
3300attggaattg ctggattaat gttattggct cgtagaagaa agaattaa
3348504410DNAStaphylococcus sp. 50atgggcaaac gtagacaagg tcctattaat
aaaaaagtgg attttttacc taacaaatta 60aacaagtatt ctataagaaa attcactgtt
ggtacggcct caatattact tggttcgaca 120cttatttttg gaagtagtag ccatgaagcg
aaagctgcag aagaaaaaca agttgatcca 180attacacaag ctaatcaaaa tgatagtagt
gaaagatcac ttgaaaacac aaatcaacct 240actgtaaaca atgaagcacc acagatgtct
tctacattgc aagcagaaga aggaagcaat 300gcagaagcac cgaatgttcc aactatcaaa
gctaattcag ataatgatac acaaacacaa 360ttttcagaag cccctacaag aaatgaccta
gctagaaaag aagatatccc tgctgtttct 420aaaaacgagg aattacaatc atcacaacca
aacactgaca gtaaaataga acctacaact 480tcagaacctg tgaatttaaa ttatagttct
ccgtttatgt ccttattaag catgcctgct 540gatagttcat ccaataacac taaaaataca
atagatatac cgccaactac ggttaaaggt 600agagataatt acgattttta cggtagagta
gatatccaaa gtaatcctac agatttaaat 660gcgacaaatt taacgagata taattatgga
cagccacctg gtacaacaac agctggtgca 720gttcaattta aaaatcaagt tagttttgat
aaagatttcg actttaacat tagagtagca 780aacaatcgtc aaagtaatac aactggtgca
gatggttggg gctttatgtt cagcaagaaa 840gatggggatg atttcctaaa aaacggtggt
atcttacgtg aaaaaggtac acctagtgca 900gctggtttca gaattgatac aggatattat
aataacgatc cattagataa aatacagaaa 960caagctggtc aaggctatag agggtatggg
acatttgtta aaaatgactc ccaaggtaat 1020acttctaaag taggatcagg tactccatca
acagattttc ttaactacgc agataatact 1080actaatgatt tagatggtaa attccatggt
caaaaattaa ataatgttaa tttgaaatat 1140aatgcttcaa atcaaacttt tacagctact
tatgctggta aaacttggac ggctacgtta 1200tctgaattag gattgagtcc aactgatagt
tacaattttt tagttacatc aagtcaatat 1260ggaaatggta atagtggtac atacgcagat
ggcgttatga gagctgattt agatggtgca 1320acattgacat atactcctaa agcagtcgat
ggagacccaa ttacatcaac taaggaaata 1380ccatttaata aaaaacgcga atttgatcca
aacttagcgc caggtacaga aaaagtcgtt 1440caaaaaggtg aaccaggaat tgaaacaaca
acaacaccaa cttatgtcaa tcctaatact 1500ggagaaaaag taggtgaagg cacacctaca
acaaagatca ctaaacaacc agtggatgaa 1560atcgttcatt atggtggcga agaaatcaag
ccaggacata aagatgaatt tgatccaaat 1620gcaccgaaag gtagtcaaac aacgcaacca
ggtaagccag gagttaaaaa tcctgataca 1680ggcgaagtag tcacaccacc agtggatgat
gtgacaaaat atggtccagt tgatggagat 1740ccgattacgt caacggaaga aattccattc
gacaagaaac gtgaattcaa tcctgattta 1800aaaccaggtg aagagcgtgt taaacaaaaa
ggtgaaccag gaacaaaaac aattacaaca 1860ccaacaacta agaacccatt aacaggggaa
aaagttggcg aaggtgaacc aacagaaaaa 1920ataacaaaac aaccagtaga tgaaatcaca
gaatatggtg gcgaagaaat caagccaggc 1980cataaggatg aatttgatcc gaacgcaccg
aaaggtagcc aagaggacgt tccaggtaaa 2040ccaggagtta aaaatcctga tacaggcgaa
gtagtcacac caccagtgga tgatgtgaca 2100aaatatggtc cagttgatgg agatccgatt
acgtcaacgg aagaaattcc gtttgataaa 2160aaacgcgaat ttgatccaaa cttagcgcca
ggtacagaga aagtcgttca aaaaggtgaa 2220ccaggaacaa aaacaattac aacaccaaca
actaagaacc cattaacagg agaaaaagtt 2280ggcgaaggtg aaccaacaga aaaaataaca
aaacaaccag tggatgaaat cgttcattat 2340ggtggcgaag aaatcaagcc aggccataag
gatgaatttg atccgaacgc accgaaaggt 2400agccaagagg acgttccagg taagccagga
gttaaaaatc ctgatacagg cgaagtagtc 2460acaccaccag tggatgatgt gacaaaatat
ggtccagttg atggagatcc gattacgtca 2520acggaagaaa ttccattcga caagaaacgt
gaattcaatc ctgatttaaa accaggtgaa 2580gagcgtgtta aacaaaaagg tgaaccagga
acaaaaacaa ttacaacacc aacaactaag 2640aacccattaa caggggaaaa agttggcgaa
ggtgaaccaa cagaaaaagt aacaaaacaa 2700ccagtggatg aaatcgttca ttatggtggc
gaagaaatca agccaggcca taaggatgaa 2760tttgatccaa atgcaccgaa aggtagccaa
gaagacgttc caggtaaacc aggagttaaa 2820aaccctgata caggcgaagt agttactcca
ccagtggatg atgtgacaaa atatggtcca 2880gttgatggag atccgattac gtcaacggaa
gaaattccgt ttgataaaaa acgcgaattt 2940gatccaaact tagcgccagg tacagagaaa
gtcgttcaaa aaggtgaacc aggaacaaaa 3000acaattacaa caccaacaac taagaaccca
ttaacaggag aaaaagttgg cgaaggtgaa 3060ccaacagaaa aaataacaaa acaaccagtg
gatgagatcg ttcattatgg tggcgaagaa 3120atcaagccag gccataagga tgaatttgat
ccgaacgcac cgaaaggtag tcaaacaacg 3180caaccaggta agccaggagt taaaaatcct
gatacaggcg aagtagtcac accaccagtg 3240gatgatgtga caaaatatgg tccagttgat
ggagatccga ttacgtcaac ggaagaaatt 3300ccgtttgata aaaaacgcga atttgatcca
aacttagcgc caggtacaga gaaagtcgtt 3360caaaaaggtg aaccaggaac aaaaacaatt
acaacgccaa caactaagaa cccattaaca 3420ggagaaaaag ttggcgaagg tgaaccaaca
gaaaaaataa caaaacaacc agtggatgag 3480attgttcatt atggtggtga acaaatacca
caaggtcata aagatgaatt tgatccaaat 3540gcacctgtag atagtaaaac tgaagttcca
ggtaaaccag gagttaaaaa tcctgataca 3600ggtgaagttg ttaccccacc agtggatgat
gtgacaaaat atggtccgaa agttggtaat 3660ccaatcacat caacggaaga gattccattt
gataagaaac gtgtatttaa tcctgattta 3720aaaccaggtg aagagcgcgt taaacaaaaa
ggtgaaccag gaacaaaaac aattacaaca 3780ccaatattag ttaatcctat tacaggagaa
aaagttggcg aaggtaaatc aacagaaaaa 3840gtcactaaac aacctgttga cgaaattgtt
gagtatggtc caacaaaagc agaaccaggt 3900aaaccagcgg aaccaggtaa accagcggaa
ccaggtaaac cagcggaacc aggtaaacca 3960gcggaaccag gtacgccagc agaaccaggt
aaaccagcgg aaccaggtaa accagcggaa 4020ccaggtaaac cagcggaacc aggtaaacca
gcggaaccag gtaaaccagc ggaaccaggt 4080acgccagcag aaccaggtaa accagcggaa
ccaggtaaac cagcggaacc aggtaaacca 4140gcggaaccag gtacgccagc agaaccaggt
aaaccagcgg aaccaggtac gccagcagaa 4200ccaggtaaac cagcggaacc aggtacgcca
acacaatcag gtgcaccaga acaaccaaat 4260agatcaatgc attcaacaga taataaaaat
caattacctg atacaggtga aaatcgtcaa 4320gctaatgagg gaactttagt cggatctcta
ttagcaattg tcggatcatt gttcatattt 4380ggtcgtcgta aaaaaggtaa tgaaaaataa
441051504DNAStaphylococcus sp.
51atgaagaaac tatatacatc ttatggcact tatggatttt tacatcaaat aaaaatcaat
60aacccgaccc atcaactatt ccaattttca gcatcagata cttcagttat ttttgaagaa
120actgatggtg agactgtttt aaaatcacct tcaatatatg aagttattaa agaaattggt
180gaattcagtg aacatcattt ctattgtgca atcttcattc cttcaacaga agatcatgca
240tatcaacttg aaaagaaact gattagtgta gacgataatt tcagaaactt tggtggcttt
300aaaagctatc gtttgttaag acctgctaaa ggtacaacat ataaaattta tttcggattt
360gctgatcgac atgcatacga agactttaag caatctgatg cctttaatga ccatttttca
420aaagacgcat taagtcatta ctttggttca agcggacaac attcaagtta ttttgaaaga
480tatctatacc caataaaaga atag
50452504DNAStaphylococcus sp. 52atgtatttat atacatctta tgggacttac
caatttttaa atcaaattaa acttaatcat 60caagaacgta gtttatttca attttccact
aatgattcct caataatctt agaagagtct 120gagggaaaat caatcttaaa acatcctagt
gcatatcaag tgattgatag cacaggtgaa 180tttaacgaac atcattttta tagtgctatt
tttgtcccta catctgaaga tcatcgtcaa 240cagctagaga aaaaattatt actcgtagac
gtacctttaa gaaattttgg tggttttaaa 300agctatcgtt tattaaaacc cactgagggg
tctacctaca aaatttactt tggttttgca 360aatcgaacag catatgaaga tttcaaagct
tctgatatat ttaatgaaaa cttttcaaaa 420gatgcattga gccaatactt tggtgctagt
ggtcaacatt ctagctactt tgaaagatat 480ttatatccaa tagaagatca ttaa
504533426DNAStaphylococcus sp.
53atgattaaca gggataataa aaaggcaata acaaaaaagg gtatgatttc aaatcgctta
60aacaaatttt cgattagaaa gtatactgta ggaactgcat cgattttagt aggtacgaca
120ttgatttttg gtctagggaa ccaagaagct aaagctgctg aaaacactag tacagaaaat
180gcgaaacaag atgatgcaac gactagtgat aataaagaag tagtgtcgga aactgaaaat
240aattcgacaa cagaaaatga ttcaacaaat ccaattaaga aagaaacaaa tactgattca
300caaccagaag ctaaagaaga atcaactaca tcaagtactc aacaacagca aaataacgtt
360acagctacaa ctgaaactaa gcctcaaaac attgaaaaag aaaatgttaa accttcaact
420gataaaactg cgacagaaga tacatctgtt attttagaag agaagaaagc accaaattat
480acaaataacg atgtaactac aaaaccatct acaagtgaaa ttcaaacaaa accaactaca
540cctcaagaat ctacaaatat tgaaaattca caaccgcaac caacgccttc aaaagtagac
600aatcaagtta cagatgcaac taatccaaaa gaaccagtaa atgtgtcaaa agaagaactt
660aaaaataatc ctgagaaatt aaaagaatta gttagaaatg ataacaatac agatcgttca
720actaaaccag ttgctacagc tccaacaagt gttgcaccaa aacgattaaa tgcgaaaatg
780cgttttgcag ttgcacaacc agcagcagtt gcttcaaata atgtaaatga cttaattaca
840gttacgaaac agacgatcaa agttggcgat ggtaaagata atgtggcagc agcgcatgac
900ggtaaagata ttgaatatga tacagagttt acaattgaca ataaagtcaa aaaaggcgat
960acaatgacga ttaattatga taagaatgta attccttcgg atttaacaga taaaaatgat
1020cctatcgata ttactgatcc atcaggagag gtcattgcca aaggaacatt tgataaagcg
1080actaagcaaa tcacatatac atttacagat tatgtagata aatatgaaga tataaaagca
1140cgtttaactt tatactcata tattgataag caagcagtac ctaatgaaac tagtttgaat
1200ttaacgtttg caacagcagg taaagaaact agccaaaacg tttctgttga ttatcaagac
1260ccaatggttc atggtgattc aaacattcaa tctatcttta caaagttaga tgaaaacaaa
1320caaactattg aacaacaaat ttatgttaat cctttgaaaa aaacagcaac taacactaaa
1380gttgatatag ctggtagtca agtagatgat tatggaaata ttaaactagg aaatggtagt
1440accattattg accaaaatac agaaataaaa gtttataaag ttaaccctaa tcaacaattg
1500cctcaaagta atagaatcta tgattttagt caatacgaag atgtaacaag tcaatttgat
1560aataaaaaat catttagtaa taatgtagca acattggatt ttggtgatat taattcagcc
1620tatattatca aagttgttag taaatataca cctacatcag atggcgaact agatattgct
1680caaggtacta gtatgagaac aactgataaa tatggttatt ataattatgc aggatattca
1740aacttcatcg taacttctaa tgacactggc ggtggcgacg gtactgttaa acctgaagaa
1800aagttataca aaattggtga ctatgtatgg gaagacgttg ataaagacgg tgtccaaggt
1860acagattcga aagaaaagcc aatggcaaac gttttagtta cattaactta cccggacggt
1920actacaaaat cagtaagaac agatgctaac ggtcattatg aattcggtgg tttgaaagac
1980ggagaaactt atacagttaa attcgaaacg ccagctggat atcttccaac aaaagtaaat
2040ggaacaactg atggtgaaaa agactcaaat ggtagttcta taactgttaa aattaatggt
2100aaagatgata tgtctttaga cactggtttt tataaagaac ctaaatataa tcttggtgac
2160tatgtatggg aagatacaaa taaagatggt atccaagatg ctaatgaacc tggtatcaaa
2220gatgttaagg ttacattaaa agatagtact ggaaaagtta ttggtacaac tactactgat
2280gcctcgggta aatataaatt tacagattta gataatggta actatacagt agaatttgaa
2340acaccagcag gttacacgcc aacggttaaa aatactacag ctgaagataa agattctaat
2400ggtttaacaa caacaggtgt cattaaagat gcagataata tgacattaga cagtggtttc
2460tataaaacac caaaatacag tttaggtgat tatgtttggt acgacagtaa taaagacggt
2520aaacaagatt caactgaaaa aggtatcaaa gatgttaaag ttactttatt aaatgaaaaa
2580ggcgaagtaa ttggaacaac taaaacagat gaaaatggta aatatcgttt cgataattta
2640gatagcggta aatacaaagt tatttttgaa aagcctgctg gcttaacaca aacagttaca
2700aatacaactg aagatgataa agatgccgat ggtggcgaag ttgacgtaac aattacggat
2760catgatgatt tcatacttga taacggatac ttcgaagaag atacatcaga cagtgattca
2820gactcagaca gtgattcaga ctcagacagc gactcagatt cagacagtga ttcagactca
2880gatagcgatt cagattcaga cagcgactca gactcagata gcgactcaga ctcagacagc
2940gactcagact cagatagcga ctcagattcg gacagcgatt cagactcaga tagcgactca
3000gattcagaca gcgattcaga ctcagatagc gactcagatt cagacagtga ctcagactca
3060gatagcgact cagactcaga cagtgactca gactcagaca gcgattcaga ttcagatagc
3120gactcagatt cggacagtga ttcagactca gatagcgact cagattcaga cagcgactca
3180gactcagata gcgactcaga ctcagacagt gattcagact cagatagcga ttcggactcg
3240gatgcaggaa aacatacacc tgttaaacca atgagtacta ctaaagacca tcacaataaa
3300gcaaaagcat taccagaaac aggtagtgaa aataacggct caaataacgc aacgttattt
3360ggtggattat ttgcagcatt aggttcatta ttgttattcg gtcgtcgcaa aaaacaaaac
3420aaataa
3426543171DNAStaphylococcus sp. 54atgattaata aaaaaaataa tttactaact
aaaaagaaac ctatagcaaa taaatccaat 60aaatatgcaa ttagaaaatt cacagtaggt
acagcgtcta ttgtaatagg tgcaacatta 120ttgtttggtt taggtcataa tgaggccaaa
gccgaggaga attcagtaca agacgttaaa 180gattcgaata cggatgatga attatcagac
agcaatgatc agtctagtga tgaagaaaag 240aatgatgtga tcaataataa tcagtcaata
aacaccgacg ataataacca aataattaaa 300aaagaagaaa cgaataacta cgatggcata
gaaaaacgct cagaagatag aacagagtca 360acaacaaatg tagatgaaaa cgaagcaaca
tttttacaaa agacccctca agataatact 420catcttacag aagaagaggt aaaagaatcc
tcatcagtcg aatcctcaaa ttcatcaatt 480gatactgccc aacaaccatc tcacacaaca
ataaatagag aagaatctgt tcaaacaagt 540gataatgtag aagattcaca cgtatcagat
tttgctaact ctaaaataaa agagagtaac 600actgaatctg gtaaagaaga gaatactata
gagcaaccta ataaagtaaa agaagattca 660acaacaagtc agccgtctgg ctatacaaat
atagatgaaa aaatttcaaa tcaagatgag 720ttattaaatt taccaataaa tgaatatgaa
aataaggcta gaccattatc tacaacatct 780gcccaaccat cgattaaacg tgtaaccgta
aatcaattag cggcggaaca aggttcgaat 840gttaatcatt taattaaagt tactgatcaa
agtattactg aaggatatga tgatagtgaa 900ggtgttatta aagcacatga tgctgaaaac
ttaatctatg atgtaacttt tgaagtagat 960gataaggtga aatctggtga tacgatgaca
gtggatatag ataagaatac agttccatca 1020gatttaaccg atagctttac aataccaaaa
ataaaagata attctggaga aatcatcgct 1080acaggtactt atgataacaa aaataaacaa
atcacctata cttttacaga ttatgtagat 1140aagtatgaaa atattaaagc acaccttaaa
ttaacgtcat acattgataa atcaaaggtt 1200ccaaataata ataccaagtt agatgtagaa
tataaaacgg ccctttcatc agtaaataaa 1260acaattacgg ttgaatatca aagacctaac
gaaaatcgga ctgctaacct tcaaagtatg 1320tttacaaaca tagatacgaa aaatcataca
gttgagcaaa cgatttatat taaccctctt 1380cgttattcag ccaaggaaac aaatgtaaat
atttcaggga atggtgatga aggttcaaca 1440attatagacg atagcacaat aattaaagtt
tataaggttg gagataatca aaatttacca 1500gatagtaaca gaatttatga ttacagtgaa
tatgaagatg tcacaaatga tgattatgcc 1560caattaggaa ataataatga tgtgaatatt
aattttggta atatagattc accatatatt 1620attaaagtta ttagtaaata tgaccctaat
aaggatgatt acacgactat acagcaaact 1680gtgacaatgc agacgactat aaatgagtat
actggtgagt ttagaacagc atcctatgat 1740aatacaattg ctttctctac aagttcaggt
caaggacaag gtgacttgcc tcctgaaaaa 1800acttataaaa tcggagatta cgtatgggaa
gatgtagata aagatggtat tcaaaataca 1860aatgataatg aaaaaccgct tagtaatgta
ttggtaactt tgacgtatcc tgatggaact 1920tcaaaatcag tcagaacaga tgaagatggg
aaatatcaat ttgatggatt gaaaaacgga 1980ttgacttata aaattacatt cgaaacacct
gaaggatata cgccgacgct taaacattca 2040ggaacaaatc ctgcactaga ctcagaaggt
aattctgtat gggtaactat taatggacaa 2100gacgatatga cgattgatag tggattttat
caaacaccta aatacagctt agggaactat 2160gtatggtatg acactaataa agatggtatt
caaggtgatg atgaaaaagg aatctctgga 2220gttaaagtga cgttaaaaga tgaaaacgga
aatatcatta gtacaactac aaccgatgaa 2280aatggaaagt atcaatttga taatttaaat
agtggtaatt atattgttca ttttgataaa 2340ccttcaggta tgactcaaac aacaacagat
tctggtgatg atgacgaaca ggatgctgat 2400ggggaagaag ttcatgtaac aattactgat
catgatgact ttagtataga taacggatac 2460tatgatgacg aatcggattc cgatagtgac
tcagacagcg actcagattc cgatagtgat 2520tcagactccg atagcgactc ggattcagac
agcgactcag attcagacag cgactcggat 2580tctgatagcg actcggattc agacagcgac
tcagactcag acagtgattc agattcagac 2640agcgactcag attccgatag tgattcagac
tcagacagcg actcagattc tgatagtgat 2700tcagactcag acagtgattc agattcagac
agcgactcag attccgatag tgattcagac 2760tcagacagcg actcagattc cgatagtgat
tcagactcag acagcgactc agattctgat 2820agtgattcag actcagacag tgattcagat
tccgatagtg attcagactc cgatagcgac 2880tcagactcgg atagtgactc agattctgat
agtgattcag actcagacag tgattcggat 2940tccgatagtg attcagactc agacagcgac
tcagattctg atagtgattc agactcagac 3000aacgactcag atttaggcaa tagctcagat
aagagtacaa aagataaatt acctgataca 3060ggagctaatg aagattatgg ctctaaaggc
acgttacttg gaactctgtt tgcaggttta 3120ggagcgttat tattagggaa acgtcgcaaa
aatagaaaaa ataaaaatta a 3171551461DNAStaphylococcus sp.
55atgtctaata attttaaaga tgactttgaa aaaaatcgtc aatcgataga cacaaattca
60catcaagacc atacggaaga tgttgaaaaa gaccaatcag aattagaaca tcaggataca
120atagagaata cggagcaaca gtttccgcca agaaatgccc aaagaagaaa aagacgccgt
180gatttagcaa cgaatcataa taaacaagtt cacaatgaat cacaaacatc tgaagacaat
240gttcaaaatg aggctggcac aatagatgat cgtcaagtcg aatcatcaca cagtactgaa
300agtcaagaac ctagccatca agacagtaca cctcaacatg aagaggaata ttataataag
360aatgcttttg caatggataa atcacatcca gaaccaatcg aagacaatga taaacacgag
420actattaaag atgcagaaaa taacactgag cattcaacag tttctgataa gagtatagct
480gaacaatctc agcaacctaa accatatttt gcaacaggtg ctaaccaagc aaatacatca
540aaagataaac atgatgatgt aactgttaag caagacaaag atgaatctaa agatcatcat
600agtggtaaaa aaggcgcagc aattggtgct ggaacagcgg gtgttgcagg tgcagctggt
660gcaatgggtg tttctaaagc taagaaacat tcaaatgacg ctcaaaacaa aagtaattct
720gacaagtcga ataactcgac tgaggataaa gcgtctcaag ataagtctaa agatcatcat
780aatggcaaaa aaggtgcagc gatcggtgct ggaacagcag gtttggctgg aggcgcagca
840agtaaaagtg cttctgccgc ttcaaaacca catgcctcta ataatgcaag ccaaaaccat
900gatgaacatg acaatcatga cagagataaa gaacgtaaaa aaggtggcat ggccaaagta
960ttgttaccat taattgcagc tgtactaatt atcggtgcat tagcgatatt tggaggcatg
1020gcattaaaca atcataataa tggtacaaaa gaaaataaaa tcgcgaatac aaataaaaat
1080aatgctgatg aaagtaaaga caaagacaca tctaaagacg cttctaaaga taaatcaaaa
1140tctacagaca gtgataaatc aaaagaggat caagacaaag cgactaaaga tgaatctgat
1200aatgatcaaa acaacgctaa tcaagcgaac aatcaagcac aaaataatca aaatcaacaa
1260caagctaatc aaaatcaaca acagcaacaa caacgtcaag gtggtggcca aagacataca
1320gtgaatggtc aagaaaactt ataccgtatc gcaattcaat actacggttc aggttcaccg
1380gaaaatgttg aaaaaattag acgtgccaat ggtttaagtg gtaacaatat tagaaacggt
1440caacaaatcg ttattccata a
1461561419DNAStaphylococcus sp. 56gtgattgaat taattaaaat ggaagggatg
atagttgtgt ctaataataa ttttaaagat 60gatttcgaaa agaatcgtca atctattaat
ccagacgaac agcaaacaga attaaaagaa 120gatgataaaa caaatgaaaa taaaaaagaa
gctgactctc aaaacagttt atctaataac 180tcaaatcaac aatttcctcc gagaaatgcc
caacgacgaa aaagacgtag agagacagca 240actaatcaaa gcaaacaaca agacgacaaa
catcaaaaaa atagtgacgc taaaactaca 300gaaggttcat tagatgaccg ttatgacgaa
gcacagttac agcaacaaca tgataaatcg 360caacaacaaa ataaaactga aaaacaatca
caagataata gaatgaaaga tggaaaagat 420gcagctattg taaatggaac atctgagtca
ccagaacata aatcaaaatc aacacaaaat 480agacccggcc ctaaagctca acaacaaaag
cgtaaatcag aaagtacgca atcaaaaccg 540tcaacaaaca aagataaaaa agcagctaca
ggtgctggaa tagctggtgc agctggtgtt 600gctggtgcag cagaaacatc caaacgtcat
cataataaaa aagataaaca agattctaaa 660cactcaaacc atgagaatga cgaaaaatct
gttaaaaatg atgaccaaaa gcaatctaaa 720aaaggcaaaa aagcagcagt cggtgctggc
gcagctgcag gagttggtgc ggctggtgtt 780gcgcatcata ataatcaaaa taaacatcat
aatgaggaaa aaaattctaa tcaaaacaat 840cagtacaatg accaatcaga aggtaagaaa
aaaggtggtt tcatgaaaat cttgttacca 900cttatagcag ccattcttat tctaggtgca
atagcaatat tcggtggtat ggctctaaat 960aatcacaacg atagtaaaag tgatgaccaa
aaaatagcga atcaaagtaa gaaagactca 1020gataaaaaag atggtgcgca atccgaagat
aacaaagaca aaaaatctga tagtaacaaa 1080gacaaaaaat ctgattctga taagaacgca
gatgatgact ctgataatag ttcctcaaat 1140cctaacgcta cttcaactaa taataacgat
aatgtagcca ataataactc aaattataca 1200aaccaaaatc aacaagataa tgcaaaccaa
aatagcaata atcaacaggc aactcaaggt 1260caacaatcac atacagtata cggtcaagaa
aacttatatc gtatcgccat acaatattat 1320ggagaaggaa ctcaagctaa cgtagataaa
attaaacgtg cgaatggatt aagcagtaat 1380aatattcata atggtcaaac attagttatt
cctcaataa 141957498DNAStaphylococcus sp.
57atgaaaaata aattgatagc aaaatcttta ttaacaatag cggcaattgg tattactaca
60actacaattg cgtcaacagc agatgcgagc gaaggatacg gtccaagaga aaagaaacca
120gtgagtatta atcacaatat cgtagagtac aatgatggta cttttaaata tcaatctaga
180ccaaaattta actcaacacc taaatatatt aaattcaaac atgactataa tattttagaa
240tttaacgatg gtacattcga atatggtgca cgtccacaat ttaataaacc agcagcgaaa
300actgatgcaa ctattaaaaa agaacaaaaa ttgattcaag ctcaaaatct tgtgagagaa
360tttgaaaaaa cacatactgt cagtgcacac agaaaagcac aaaaggcagt caacttagtt
420tcgtttgaat acaaagtgaa gaaaatggtc ttacaagagc gaattgataa tgtattaaaa
480caaggattag tgagataa
49858960DNAStaphylococcus sp. 58atgaaaacac gtatagtcag ctcagtaaca
acaacactat tgctaggttc catattaatg 60aatcctgtcg ctaatgccgc agattctgat
attaatatta aaaccggtac tacagatatt 120ggaagcaata ctacagtaaa aacaggtgat
ttagtcactt atgataaaga aaatggcatg 180cacaaaaaag tattttatag ttttatcgat
gataaaaatc acaataaaaa actgctagtt 240attagaacga aaggtaccat tgctggtcaa
tatagagttt atagcgaaga aggtgctaac 300aaaagtggtt tagcctggcc ttcagccttt
aaggtacagt tgcaactacc tgataatgaa 360gtagctcaaa tatctgatta ctatccaaga
aattcgattg atacaaaaga gtatatgagt 420actttaactt atggattcaa cggtaatgtt
actggtgatg atacaggaaa aattggcggc 480cttattggtg caaatgtttc gattggtcat
acactgaaat atgttcaacc tgatttcaaa 540acaattttag agagcccaac tgataaaaaa
gtaggctgga aagtgatatt taacaatatg 600gtgaatcaaa attggggacc atatgataga
gattcttgga acccggtata tggcaatcaa 660cttttcatga aaactagaaa tggttctatg
aaagcagcag agaacttcct tgatcctaac 720aaagcaagtt ctctattatc ttcagggttt
tcaccagact tcgctacagt tattactatg 780gatagaaaag catccaaaca acaaacaaat
atagatgtaa tatacgaacg agttcgtgat 840gactaccaat tgcattggac ttcaacaaat
tggaaaggta ccaatactaa agataaatgg 900acagatcgtt cttcagaaag atataaaatc
gattgggaaa aagaagaaat gacaaattaa 960591287DNAStaphylococcus sp.
59atacacatga aaaataaata tatctcgaag ttgctagttg gggcagcaac aattacttta
60gctacaatga tttcaaatgg ggaagcaaaa gcgagtgaaa acacgcaaca aacttcaact
120aagcaccaaa caactcaaaa caactacgta acagatcaac aaaaagcttt ttatcaagta
180ttacatctaa aaggtatcac agaagaacaa cgtaaccaat acatcaaaac attacgcgaa
240cacccagaac gtgcacaaga agtattctct gaatcactta aagacagcaa gaacccagac
300cgacgtgttg cacaacaaaa cgctttttac aatgttctta aaaatgataa cttaactgaa
360caagaaaaaa ataattacat tgcacaaatt aaagaaaacc ctgatagaag ccaacaagtt
420tgggtagaat cagtacaatc ttctaaagct aaagaacgtc aaaatattga aaatgcggat
480aaagcaatta aagatttcca agataacaaa gcaccacacg ataaatcagc agcatatgaa
540gctaactcaa aattacctaa agatttacgc gataaaaata accgctttgt agaaaaagtt
600tcaattgaaa aagcaatcgt tcgtcatgat gagcgtgtga aatcagcaaa tgatgcaatc
660tcaaaattaa atgaaaaaga ttcaattgaa aacagacgtt tagcacaacg tgaagttaac
720aaagcaccta tggatgtaaa agagcattta cagaaacaat tagacgcatt agtagctcaa
780aaagatgctg aaaagaaagt ggcgccaaaa gttgaggctc ctcaaattca atcaccacaa
840attgaaaaac ctaaagcaga atcaccaaaa gttgaagtcc ctcaatctaa attattaggt
900tactaccaat cattaaaaga ttcatttaac tatggttaca agtatttaac agatacttat
960aaaagctata aagaaaaata tgatacagca aagtactact ataatacgta ctataaatac
1020aaaggtgcga ttgatcaaac agtattaaca gtactaggta gtggttctaa atcttacatc
1080caaccattga aagttgatga taaaaacggc tacttagcta aatcatatgc acaagtaaga
1140aactatgtaa ctgagtcaat caatactggt aaagtattat atactttcta ccaaaaccca
1200acattagtaa aaacagctat taaagctcaa gaaactgcat catcaatcaa aaatacatta
1260agtaatttat tatcattctg gaaataa
1287601053DNAStaphylococcus sp. 60atgacaaaac attatttaaa cagtaagtat
caatcagaac aacgttcatc agctatgaaa 60aagattacaa tgggtacagc atctatcatt
ttaggttccc ttgtatacat aggcgcagac 120agccaacaag tcaatgcggc aacagaagct
acgaacgcaa ctaataatca aagcacacaa 180gtttctcaag caacatcaca accaattaat
ttccaagtgc aaaaagatgg ctcttcagag 240aagtcacaca tggatgacta tatgcaacac
cctggtaaag taattaaaca aaataataaa 300tattatttcc aaaccgtgtt aaacaatgca
tcattctgga aagaatacaa attttacaat 360gcaaacaatc aagaattagc aacaactgtt
gttaacgata ataaaaaagc ggatactaga 420acaatcaatg ttgcagttga acctggatat
aagagcttaa ctactaaagt acatattgtc 480gtgccacaaa ttaattacaa tcatagatat
actacgcatt tggaatttga aaaagcaatt 540cctacattag ctgacgcagc aaaaccaaac
aatgttaaac cggttcaacc aaaaccagct 600caacctaaaa cacctactga gcaaactaaa
ccagttcaac ctaaagttga aaaagttaaa 660cctactgtaa ctacaacaag caaagttgaa
gacaatcact ctactaaagt tgtaagtact 720gacacaacaa aagatcaaac taaaacacaa
actgctcata cagttaaaac agcacaaact 780gctcaagaac aaaataaagt tcaaacacct
gttaaagatg ttgcaacagc gaaatctgaa 840agcaacaatc aagctgtaag tgataataaa
tcacaacaaa ctaacaaagt tacaaaacat 900aacgaaacgc ctaaacaagc atctaaagct
aaagaattac caaaaactgg tttaacttca 960gttgataact ttattagcac agttgccttc
gcaacacttg cccttttagg ttcattatct 1020ttattacttt tcaaaagaaa agaatctaaa
taa 1053611938DNAStaphylococcus sp.
61atgaacaaac agcaaaaaga atttaaatca ttttattcaa ttagaaagtc atcactaggc
60gttgcatctg tagcgattag tacactttta ttattaatgt caaatggcga agcacaagca
120gcagctgaag aaacaggtgg tacaaataca gaagcacaac caaaaactga agcagttgca
180agtccaacaa caacatctga aaaagctcca gaaactaaac cagtagctaa tgctgtctca
240gtatctaata aagaagttga ggcccctact tctgaaacaa aagaagctaa agaagttaaa
300gaagttaaag cccctaagga aacaaaagca gttaaaccag cagcaaaagc cactaacaat
360acatatccta ttttgaatca ggaacttaga gaagcgatta aaaaccctgc aataaaagat
420aaagatcata gcgcaccaaa ctctcgtcca attgattttg aaatgaaaaa agaaaatggt
480gagcaacaat tttatcatta tgccagctct gttaaacctg ctagagttat tttcactgat
540tcaaaaccag aaattgaatt aggattacaa tcaggtcaat tttggagaaa atttgaagtt
600tatgaaggtg acaaaaagtt gccaattaaa ttagtatcat acgatactgt taaagattac
660gcttacattc gcttctctgt ttcaaatgga acaaaagccg ttaaaattgt aagttcaact
720cacttcaata acaaagaaga aaaatacgat tacacattaa tggaattcgc acaaccaatt
780tataacagtg cagataaatt caaaactgaa gaagattata aagctgaaaa attattagcg
840ccatataaaa aagcgaaaac actagaaaga caagtttatg aattaaataa aattcaagat
900aaacttcctg aaaaattaaa ggctgagtac aagaagaaat tagaggatac aaagaaagct
960ttagatgagc aagtgaaatc agctattact gaattccaaa atgtacaacc aacaaatgaa
1020aaaatgactg atttacaaga tacaaaatat gttgtttatg aaagtgttga gaataacgaa
1080tctatgatgg atacttttgt taaacaccct attaaaacag gtatgcttaa cggcaaaaaa
1140tatatggtca tggaaactac taatgacgat tactggaaag atttcatggt tgaaggtcaa
1200cgtgttagaa ctataagcaa agatgctaaa aataatacta gaacaattat tttcccatat
1260gttgaaggta aaactctata tgatgctatc gttaaagttc acgtaaaaac gattgattat
1320gatggacaat accatgtcag aatcgttgat aaagaagcat ttacaaaagc caataccgat
1380aaatctaaca aaaaagaaca acaagataac tcagctaaga aggaagctac tccagctacg
1440cctagcaaac caacaccatc acctgttgaa aaagaatcac aaaaacaaga cagccaaaaa
1500gatgacaata aacaattacc aagtgttgaa aaagaaaatg acgcatctag tgagtcaggt
1560aaagacaaaa cgcctgctac aaaaccaact aaaggtgaag tagaatcaag tagtacaact
1620ccaactaagg tagtatctac gactcaaaat gttgcaaaac caacaactgc ttcatcaaaa
1680acaacaaaag atgttgttca aacttcagca ggttctagcg aagcaaaaga tagtgctcca
1740ttacaaaaag caaacattaa aaacacaaat gatggacaca ctcaaagcca aaacaataaa
1800aatacacaag aaaataaagc aaaatcatta ccacaaactg gtgaagaatc aaataaagat
1860atgacattac cattaatggc attactagct ttaagtagca tcgttgcatt cgtattacct
1920agaaaacgta aaaactaa
1938622862DNAStaphylococcus sp. 62atgaataata aaaagacagc aacaaataga
aaaggcatga taccaaatcg attaaacaaa 60ttttcgataa gaaagtattc tgtaggtact
gcttcaattt tagtagggac aacattgatt 120tttgggttaa gtggtcatga agctaaagcg
gcagaacata cgaatggaga attaaatcaa 180tcaaaaaatg aaacgacagc cccaagtgag
aataaaacaa ctgaaaaagt tgatagtcgt 240caactaaaag acaatacgca aactgcaact
gcagatcagc ctaaagtgac aatgagtgat 300agtgcaacag ttaaagaaac tagtagtaac
atgcaatcac cacaaaacgc tacagctagt 360caatctacta cacaaactag caatgtaaca
acaaatgata aatcatcaac tacatatagt 420aatgaaactg ataaaagtaa tttaacacaa
gcaaaaaacg tttcaactac acctaaaaca 480acgactatta aacaaagagc tttaaatcgc
atggcagtga atactgttgc agctccacaa 540caaggaacaa atgttaatga taaagtacat
tttacgaaca ttgatattgc gattgataaa 600ggacatgtta ataaaacaac aggaaatact
gaattttggg caacttcaag tgatgtttta 660aaattaaaag cgaattacac aatcgatgat
tctgttaaag agggcgatac atttactttt 720aaatatggtc aatatttccg tccaggttct
gtaagattac cttcacaaac tcaaaattta 780tataatgccc aaggtaatat tattgcaaaa
ggtatttacg atagtaaaac aaatacaaca 840acgtatactt ttacgaatta tgtagatcaa
tacacaaatg ttagcggtag ctttgaacaa 900gtcgcatttg cgaaacgtga aaatgcaaca
actgataaaa ctgcttataa aatggaagta 960actttaggta atgatacata tagtaaagat
gtcattgtcg attatggtaa tcaaaaaggt 1020caacaactta tttcgagtac aaattatatt
aataatgaag atttgtcacg taatatgact 1080gtttatgtaa atcaacctaa aaagacctat
acaaaagaaa catttgtaac aaatttaact 1140ggttataaat ttaatccaga tgctaaaaac
ttcaaaattt acgaagtgac agatcaaaat 1200caatttgtgg atagtttcac cccagatact
tcaaaactta aagatgttac tggtcaattc 1260gatgttattt atagtaatga taataagacg
gcgacagtag atttattgaa tggtcaatct 1320agtagtgata aacagtacat cattcaacaa
gttgcttatc cagataatag ttcaacagat 1380aatgggaaaa ttgattatac tttagaaaca
caaaatggaa aaagtagttg gtcaaacagt 1440tattcaaatg tgaatggctc atcaactgca
aatggcgacc aaaagaaata taatctaggt 1500gactatgtat gggaagatac aaataaagat
ggtaaacaag atgccaatga aaaagggatt 1560aaaggtgttt atgtcattct taaagatagt
aacggtaaag aattagatcg tacgacaaca 1620gatgaaaatg gtaaatatca gttcactggt
ttaagcaatg gaacttatag tgtagagttt 1680tcaacaccag ccggttatac accgacaact
gcaaatgcag gtacagatga tgctgtagat 1740tctgatggac taactacaac aggtgtcatt
aaagacgctg acaacatgac attagatagt 1800ggattctaca aaacaccaaa atatagttta
ggtgattatg tttggtacga cagtaataaa 1860gatggtaaac aagattcgac tgaaaaagga
attaaaggtg ttaaagttac tttgcaaaac 1920gaaaaaggcg aagtaattgg tacaactgaa
acagatgaaa atggtaaata ccgctttgat 1980aatttagata gtggtaaata caaagttatc
tttgaaaagc ctgctggttt aactcaaaca 2040ggtacaaata caactgaaga tgataaagat
gccgatggtg gcgaagttga tgtaacaatt 2100acggatcatg atgatttcac acttgataat
ggctactacg aagaagaaac atcagatagt 2160gactcagatt cggacagcga ttcagactca
gatagcgact cagattcaga tagtgactca 2220gactcagata gcgactcaga ctcagatagc
gactcagaca gcgactcaga ctcagatagt 2280gattcagatt cggacagcga ctcagattca
gacagcgaat cagattcgga tagcgactca 2340gactcagata gcgactcaga cagcgactca
gattcagaca gtgactcaga ctcagacagc 2400gactcagatt cagacagcga ttcagattcg
gatagcgact cagattcaga tagcgattcg 2460gactcagaca acgactcaga ttctgacagc
gattcagact cagatagcga ctcagattca 2520gacagcgact cagattcaga cagcgattca
gattcagata gcgattcaga ttcagacagc 2580gactcagatt cagatagcga ctcagactca
gacagcgatt cagactcaga tagcgactca 2640gacagcgatt cagattcgga tagcgattca
gattcagatg caggtaaaca tactccgact 2700aaaccaatga gtacggttaa agatcagcat
aaaacagcta aagcattacc agaaacaggt 2760agtgaaaata ataattcaaa taatggcaca
ttattcggtg gattattcgc ggcattagga 2820tcattattgt tattcggtcg tcgtaaaaaa
caaaataaat aa 2862632808DNAStaphylococcus sp.
63atgaatatga agaaaaaaga aaaacacgca attcggaaaa aatcgattgg cgtggcttca
60gtgcttgtag gtacgttaat cggttttgga ctactcagca gtaaagaagc agatgcaagt
120gaaaatagtg ttacgcaatc tgatagcgca agtaacgaaa gcaaaagtaa tgattcaagt
180agcgttagtg ctgcacctaa aacagacgac acaaacgtga gtgatactaa aacatcgtca
240aacactaata atggcgaaac gagtgtggcg caaaatccag cacaacagga aacgacacaa
300tcatcatcaa caaatgcaac tacggaagaa acgccggtaa ctggtgaagc tactactacg
360acaacgaatc aagctaatac accggcaaca actcaatcaa gcaatacaaa tgcggaggaa
420ttagtgaatc aaacaagtaa tgaaacgact tctaatgata ctaatacagt atcatctgta
480aattcacctc aaaattctac aaatgcggaa aatgtttcaa caacgcaaga tacttcaact
540gaagcaacac cttcaaacaa tgaatcagct ccacagaata cagatgcaag taataaagat
600gtagttagtc aagcggttaa tccaagtacg cctagaatga gagcatttag tttagcggca
660gtagctgcag atgcaccggc agctggcaca gatattacga atcagttgac agatgtgaaa
720gttactattg actctggtac gactgtgtat ccgcaccaag caggttatgt caaactgaat
780tatggttttt cagtgcctaa ttctgctgtt aaaggtgaca cattcaaaat aactgtacct
840aaagaattaa acttaaatgg tgtaacttca actgctaaag tgccaccaat tatggctgga
900gatcaagtat tggcaaatgg tgtaatcgat agtgatggta atgttattta tacatttaca
960gactatgttg ataataaaga aaatgtaaca gctaatatta ctatgccagc ttatattgac
1020cctgaaaatg ttacaaagac aggtaatgtg acattgacaa ctggcatagg aaccaatact
1080gctagtaaga cagtattaat cgactatgag aaatatggac aattccataa tttatcaatt
1140aaaggtacga ttgatcaaat cgataaaaca aataatacgt atcgccaaac aatttatgtc
1200aatccaagcg gagataacgt tgtgttacct gccttaacag gtaatttaat tcctaataca
1260aagagtaatg cgttaataga tgcaaaaaac actgatatta aagtttatag agtcgataat
1320gctaatgatt tatctgaaag ttattatgtg aatcctagcg attttgaaga tgtaactaat
1380caagttagaa tttcatttcc aaatgctaat caatacaaag tagaatttcc tacggacgat
1440gaccaaatta caacaccgta tattgtagtt gttaatggcc atattgatcc tgctagtaca
1500ggtgatttag cactacgttc gacattttat ggttatgatt ctaattttat atggagatct
1560atgtcatggg acaacgaagt agcatttaat aacggatcag gttctggtga cggtatcgat
1620aaaccagttg ttcctgaaca acctgatgag cctggtgaaa ttgaaccaat tccagaggat
1680tcagattctg acccaggttc agattctggc agcgattcta attcagatag cggttcagat
1740tctggcagtg attctacatc agatagtggt tcagattcag cgagtgattc agattcagca
1800agtgattcag actcagcgag tgattcagat tcagcaagtg attcagattc agcaagtgat
1860tcagattcag caagtgattc agactcagca agtgattcag attcagcaag tgattcagat
1920tcagcaagcg attcagattc agcgagcgat tcagattcag cgagcgattc agattcagcg
1980agtgattccg actcagcgag cgattcagac tcagatagtg actcagattc cgatagcgat
2040tccgactcag atagcgactc agattcagac agcgattctg actcagacag cgattctgac
2100tcagacagtg actcagattc cgatagcgat tctgactcag acagtgactc agattccgat
2160agcgattcag attcagacag tgattcagac tcagatagcg attcagattc cgacagtgac
2220tcagactcag acagcgattc agattccgat agcgattcag attccgacag tgactcagat
2280tccgatagtg actcggattc agcgagtgat tcagattcag atagcgattc agaatcagat
2340agtgactcag actcagacag tgattcagat tcagatagtg actcagactc agacagcgat
2400tcagaatcag atagtgactc cgattcagac agcgattcag aatcagatag tgactccgat
2460tcagatagcg attcggattc agcgagtgat tcagactcag gtagtgactc cgattcatca
2520agtgattcag attccgattc aacgagtgac acaggatcag acaacgactc agacagtgat
2580tcaaatagcg attccgagtc aggttctaac aataatgtag ttccgcctaa ttcacctaaa
2640aatggtacta atgcttctaa taaaaatgag gctaaagata gtaaagaacc attaccagat
2700acaggttctg aagatgaagc gaatacgtca ctaatttggg gattattagc atcattaggt
2760tcattactac ttttcagaag aaaaaaagaa aataaagata agaaataa
2808643117DNAStaphylococcus sp. 64gtgaaaaaca atcttaggta cggcattaga
aaacataaat tgggagcagc atcagtattc 60ttaggaacaa tgatcgttgt tgggatggga
caagataaag aagctgcagc atcagaacaa 120aagacaacta cagtagaaga aaatgggaat
tcagctactg ataataaaac aagtgaaaca 180caaacaactg ctactaacgt taatcatata
gaagaaactc aatcatataa cgcaacagta 240acagaacaac cgtcaaacgc aacacaagta
acaactgaag aagcaccaaa agcagtacaa 300gcaccacaaa ctgcacaacc agcaaatgta
gaaacagtta aagaagaaga gaaacctcaa 360gttaaggaaa cgacacaacc tcaagacaat
agcggaaatc aaagacaagt agatttaaca 420cctaaaaagg ttacacaaaa tcaagggaca
gaaacacaag ttgaagtggc acagccaaga 480acggcatcag aaagtaagcc acgtgtgaca
agatcagcag atgtagcgga agctaaggaa 540gctagtgacg tttcagaagt taaaggcaca
gatgttacaa gtaaagttac agtagaaagt 600ggttctattg aggcacctca aggaaataaa
gtagagccac atgctggtca acgtgtcgta 660ttgaaataca aattgaaatt cgcagatgga
ttaaaaagag gagattattt tgattttaca 720ttatcaaata atgtaaatac ttatggggtt
tcaacagcta gaaaggtacc agagattaaa 780aatggctcag ttgtaatggc tacaggtgag
atcttaggga atggtaacat aagatataca 840tttactaacg aaattgaaca caaggtagag
gtaacagcta atttagaaat caacttattt 900attgacccta aaactgtaca aagcaatgga
gaacaaaaga ttacttctaa attaaatggt 960gaagaaacag aaaaaacaat accagttgtt
tataatccag gtgttagcaa tagttataca 1020aatgtaaatg gatcaattga aacatttaat
aaagaatcta ataaatttac acatatagct 1080tatattaagc caatgaatgg aaaccagtca
aacactgtat cagtaacagg gacgttgact 1140gaaggtagta atttagctgg tggacaacct
actgttaaag tatatgaata tctagggaaa 1200aaagatgaat tgccacaaag tgtttatgca
aatacatcag atactaacaa attcaaagat 1260gtaacaaagg aaatgaatgg aaaattgagt
gtgcaagaca atggtagtta ctcattgaat 1320ttagataagt tggataaaac gtatgtcatt
cattatacag gtgaatattt gcaagggtca 1380gatcaggtta attttagaac tgaattatat
gggtatccag aacgagcata taaatcttac 1440tatgtttatg ggggatatcg tttaacttgg
gataatggtt tagttttata tagcaataaa 1500gctgacggca atggtaaaaa tggacaaatt
attcaagata atgattttga atataaagaa 1560gatactgcaa aaggaactat gagcgggcag
tacgatgcca agcaaattat tgaaacagaa 1620gaaaatcaag acaatacacc gcttgacatt
gattaccaca cagctataga tggtgagggt 1680ggttatgttg atgggtatat tgaaacaata
gaagaaacgg attcatcagc tattgatatc 1740gattaccata ctgctgtgga tagtgaagtg
ggtcacgttg gaggatacac tgagtcctct 1800gaggaatcaa atccaattga ctttgaagaa
tcgacacatg aaaattcaaa acatcacgct 1860gatgttgttg aatatgaaga ggatacaaat
ccaggtggtg gccaagtaac aactgagtct 1920aacttagttg aatttgacga agagtctaca
aaaggtattg taactggcgc agtgagcgac 1980catacaacaa ttgaagatac gaaagaatat
acgactgaaa gtaatctgat tgaactagta 2040gatgaactac ctgaagaaca tggtcaagca
caaggaccaa tcgaggaaat tactgaaaac 2100aatcatcata tttctcattc tggtttagga
actgaaaatg gtcacggtaa ttatggcgtg 2160attgaagaaa tcgaagaaaa tagccacgtt
gatattaaga gtgaattagg ttacgaaggt 2220ggccaaaata gcggtaacca gtcattcgag
gaagacacag aagaagacaa acctaaatat 2280gaacaaggtg gcaatatcgt agatatcgat
ttcgacagtg tacctcaaat tcatggtcaa 2340aataaaggtg accagtcatt cgaagaagat
acagagaaag acaagcctaa atatgaacat 2400ggcggtaata tcattgatat cgacttcgac
agtgtgccac aaattcatgg attcaataag 2460cataatgaaa ttattgaaga agatacaaac
aaagataaac ctaattatca attcggtgga 2520cacaatagtg ttgactttga agaagataca
cttccaaaag taagcggcca aaatgaaggt 2580caacaaacga ttgaagaaga tacaacgccg
ccaacgccac cgacaccaga agtaccgagt 2640gagccggaaa caccaatgcc accgacacca
gaagtaccga gtgagccgga aacaccaacg 2700ccaccaacac cagaggtacc aagtgagccg
gaaacaccaa caccaccgac tccggaagta 2760ccaagtgagc cggaaacacc aacaccaccg
acaccagaag tgccgagtga gccagaaaca 2820ccaacaccgc caacaccaga ggtaccagct
gaacctggta aaccagtacc acccgcaaaa 2880gaagaaccta aaaagccttc taaaccagtg
gaacaaggta aagtagtaac acctgttatt 2940gaaatcaatg aaaaggttaa agcagtggca
ccaactaaaa aagcacaatc taagaaatct 3000gaactacctg aaacaggtgg agaagaatca
acaaacaaag gtatgttgtt cggcggatta 3060ttcagcattc taggtttagc attattacgc
agaaataaaa agaataacaa agcataa 3117652634DNAStaphylococcus sp.
65ttgaaaaaaa gaattgatta tttgtcgaat aagcagaata agtattcgat tagacgtttt
60acagtaggta ccacatcagt aatagtaggg gcaactatac tatttgggat aggcaatcat
120caagcacaag cttcagaaca atcgaacgat acaacgcaat cttcgaaaaa taatgcaagt
180gcagattccg aaaaaaacaa tatgatagaa acacctcaat taaatacaac ggctaatgat
240acatctgata ttagtgcaaa cacaaacagt gcgaatgtag atagcacaac aaaaccaatg
300tctacacaaa cgagcaatac cactacaaca gagccagctt caacaaatga aacacctcaa
360ccgacggcaa ttaaaaatca agcaactgct gcaaaaatgc aagatcaaac tgttcctcaa
420gaagcaaatt ctcaagtaga taataaaaca acgaatgatg ctaatagcat agcaacaaac
480agtgagctta aaaattctca aacattagat ttaccacaat catcaccaca aacgatttcc
540aatgcgcaag gaactagtaa accaagtgtt agaacgagag ctgtacgtag tttagctgtt
600gctgaaccgg tagtaaatgc tgctgatgct aaaggtacaa atgtaaatga taaagttacg
660gcaagtaatt tcaagttaga aaagactaca tttgacccta atcaaagtgg taacacattt
720atggcggcaa attttacagt gacagataaa gtgaaatcag gggattattt tacagcgaag
780ttaccagata gtttaactgg taatggagac gtggattatt ctaattcaaa taatacgatg
840ccaattgcag acattaaaag tacgaatggc gatgttgtag ctaaagcaac atatgatatc
900ttgactaaga cgtatacatt tgtctttaca gattatgtaa ataataaaga aaatattaac
960ggacaatttt cattaccttt atttacagac cgagcaaagg cacctaaatc aggaacatat
1020gatgcgaata ttaatattgc ggatgaaatg tttaataata aaattactta taactatagt
1080tcgccaattg caggaattga taaaccaaat ggcgcgaaca tttcttctca aattattggt
1140gtagatacag cttcaggtca aaacacatac aagcaaacag tatttgttaa ccctaagcaa
1200cgagttttag gtaatacgtg ggtgtatatt aaaggctacc aagataaaat cgaagaaagt
1260agcggtaaag taagtgctac agatacaaaa ctgagaattt ttgaagtgaa tgatacatct
1320aaattatcag atagctacta tgcagatcca aatgactcta accttaaaga agtaacagac
1380caatttaaaa atagaatcta ttatgagcat ccaaatgtag ctagtattaa atttggtgat
1440attactaaaa catatgtagt attagtagaa gggcattacg acaatacagg taagaactta
1500aaaactcagg ttattcaaga aaatgttgat cctgtaacaa atagagacta cagtattttc
1560ggttggaata atgagaatgt tgtacgttat ggtggtggaa gtgctgatgg tgattcagca
1620gtaaatccga aagacccaac tccagggccg ccggttgacc cagaaccaag tccagaccca
1680gaaccagaac caacgccaga tccagaacca agtccagacc cagaaccgga accaagccca
1740gacccggatc cggattcgga ttcagacagt gactcaggct cagacagcga ctcaggttca
1800gatagcgact cagaatcaga tagcgattcg gattcagaca gtgattcaga ttcagacagc
1860gactcagaat cagatagcga ttcagaatca gatagcgact cagattcaga tagcgattca
1920gattcagata gcgattcaga atcagatagc gattcggatt cagacagtga ttcagattca
1980gacagcgact cagaatcaga tagcgactca gaatcagata gtgagtcaga ttcagacagt
2040gactcggact cagacagtga ttcagactca gatagcgatt cagactcaga tagcgattca
2100gactcagaca gcgattcaga ttcagacagc gactcagaat cagacagcga ctcagactca
2160gatagcgact cagactcaga cagcgactca gattcagata gcgattcaga ctcagacagc
2220gactcagact cagacagcga ctcagactca gatagcgatt cagactcaga cagcgactca
2280gattcagata gcgattcgga ctcagacagc gattcagatt cagacagcga ctcagactcg
2340gatagcgatt cagattcaga cagcgactca gactcggata gcgactcgga ttcagatagt
2400gactccgatt caagagttac accaccaaat aatgaacaga aagcaccatc aaatcctaaa
2460ggtgaagtaa accattctaa taaggtatca aaacaacaca aaactgatgc tttaccagaa
2520acaggagata agagcgaaaa cacaaatgca actttatttg gtgcaatgat ggcattatta
2580ggatcattac tattgtttag aaaacgcaag caagatcata aagaaaaagc gtaa
2634661977DNAStaphylococcus sp. 66atgaaaaagc aaataatttc gctaggcgca
ttagcagttg catctagctt atttacatgg 60gataacaaag cagatgcgat agtaacaaag
gattatagta aagaatcaag agtgaatgag 120aaaagtaaaa agggagctac tgtttcagat
tattactatt ggaaaataat tgatagttta 180gaggcacaat ttactggagc aatagactta
ttggaagatt ataaatatgg agatcctatc 240tataaagaag cgaaagatag attgatgaca
agagtattag gagaagacca gtatttatta 300aagaaaaaga ttgatgaata tgagctttat
aaaaagtggt ataaaagttc aaataagaac 360actaatatgc ttactttcca taaatataat
ctttacaatt taacaatgaa tgaatataac 420gatattttta actctttgaa agatgcagtt
tatcaattta ataaagaagt taaagaaata 480gagcataaaa atgttgactt gaagcagttt
gataaagatg gagaagacaa ggcaactaaa 540gaagtttatg accttgtttc tgaaattgat
acattagttg taacttatta tgctgataag 600gattatgggg agcatgcgaa agagttacga
gcaaaactgg acttaatcct tggagataca 660gacaatccac ataaaattac aaatgagcgt
ataaaaaaag aaatgatcga tgacttaaat 720tcaattatag atgatttctt tatggagact
aaacaaaata gaccgaattc tataacaaaa 780tatgatccaa caaaacacaa ttttaaagag
aagagtgaaa ataaacctaa ttttgataaa 840ttagttgaag aaacaaaaaa agcagttaaa
gaagcagacg aatcttggaa aaataaaact 900gtcaaaaaat acgaggaaac tgtaacaaaa
tctcctgttg taaaagaaga gaagaaagtt 960gaagaacctc aattacctaa agttggaaac
cagcaagagg ttaaaactac ggctggtaaa 1020gctgaagaaa caacacaacc agtggcacag
ccattagtaa aaattccaca agaaacaatc 1080tatggtgaaa ctgtaaaagg tccagaatat
ccaacgatgg aaaataaaac gttacaaggt 1140gaaatcgttc aaggtcccga ttttctaaca
atggaacaaa acagaccatc tttaagcgat 1200aattatactc aaccgacgac accgaaccct
attttagaag gtcttgaagg tagctcatct 1260aaacttgaaa taaaaccaca aggtactgaa
tcaacgttga aaggtattca aggagaatca 1320agtgatattg aagttaaacc tcaagcaact
gaaacaacag aagcttctca atatggtccg 1380agaccgcaat ttaacaaaac acctaagtat
gtgaaatata gagatgctgg tacaggtatc 1440cgtgaataca acgatggaac atttggatat
gaagcgagac caagattcaa caagccaagt 1500gaaacaaatg catacaacgt aacgacaaat
caagatggca cagtatcata cggagctcgc 1560ccaacacaaa acaagccaag tgaaacaaac
gcatataacg taacaacaca tgcaaatggt 1620caagtatcat acggtgctcg cccaacacaa
aaaaagccaa gcaaaacaaa tgcatacaac 1680gtaacaacac atgcaaatgg tcaagtatca
tatggcgctc gcccgacaca aaaaaagcca 1740agcaaaacaa atgcatataa cgtaacaaca
catgcaaatg gtcaagtatc atacggagct 1800cgcccgacat acaagaagcc aagcgaaaca
aatgcataca acgtaacaac acatgcaaat 1860ggtcaagtat catatggcgc tcgcccgaca
caaaaaaagc caagcgaaac aaacgcatat 1920aacgtaacaa cacatgcaga tggtactgcg
acatatgggc ctagagtaac aaaataa 197767961PRTStaphylococcus sp. 67Met
Lys Ser Asn Leu Arg Tyr Gly Ile Arg Lys His Lys Leu Gly Ala1
5 10 15 Ala Ser Val Phe Leu Gly
Thr Met Ile Val Val Gly Met Gly Gln Glu 20 25
30 Lys Glu Ala Ala Ala Ser Glu Gln Asn Asn Thr
Thr Val Glu Glu Ser 35 40 45
Gly Ser Ser Ala Thr Glu Ser Lys Ala Ser Glu Thr Gln Thr Thr Thr
50 55 60 Asn Asn Val
Asn Thr Ile Asp Glu Thr Gln Ser Tyr Ser Ala Thr Ser65 70
75 80 Thr Glu Gln Pro Ser Lys Ser Thr
Gln Val Thr Thr Glu Glu Ala Pro 85 90
95 Thr Thr Val Gln Ala Pro Lys Val Glu Thr Glu Met Lys
Ser Gln Glu 100 105 110
Asp Leu Pro Ser Glu Lys Val Ala Asp Lys Glu Thr Thr Gly Thr Gln
115 120 125 Val Asp Ile Ala
Gln Pro Ser Asn Val Ser Glu Ile Lys Pro Arg Met 130
135 140 Lys Arg Ser Ala Asp Val Thr Ala
Val Ser Glu Lys Glu Val Ala Glu145 150
155 160 Glu Ala Lys Ala Thr Gly Thr Asp Val Thr Asn Lys
Val Glu Val Thr 165 170
175 Glu Ser Ser Leu Glu Gly His Asn Lys Asp Ser Asn Ile Val Asn Pro
180 185 190 His Asn Ala
Gln Arg Val Thr Leu Lys Tyr Lys Trp Lys Phe Gly Glu 195
200 205 Gly Ile Lys Ala Gly Asp Tyr Phe
Asp Phe Thr Leu Ser Asp Asn Val 210 215
220 Glu Thr His Gly Ile Ser Thr Leu Arg Lys Val Pro Glu
Ile Lys Ser225 230 235
240 Ser Thr Glu Asp Lys Val Met Ala Asn Gly Gln Val Ile Asn Glu Arg
245 250 255 Thr Ile Arg Tyr
Thr Phe Thr Asp Tyr Ile Asn Asn Lys Lys Asp Leu 260
265 270 Thr Ala Glu Leu Asn Leu Asn Leu Phe
Ile Asp Pro Thr Thr Val Thr 275 280
285 Lys Gln Gly Ser Gln Lys Val Glu Val Thr Leu Gly Gln Asn
Lys Val 290 295 300
Ser Lys Glu Phe Asp Ile Lys Tyr Leu Asp Gly Val Lys Asp Arg Met305
310 315 320 Gly Val Thr Val Asn
Gly Arg Ile Asp Thr Leu Asn Lys Glu Glu Gly 325
330 335 Lys Phe Ser His Phe Ala Tyr Val Lys Pro
Asn Asn Gln Ser Leu Thr 340 345
350 Ser Val Thr Val Thr Gly Gln Val Thr Ser Gly Tyr Lys Gln Ser
Ala 355 360 365 Asn
Asn Pro Thr Val Lys Val Tyr Lys His Ile Gly Ser Asp Glu Leu 370
375 380 Ala Glu Ser Val Tyr Ala
Lys Leu Asp Asp Thr Ser Lys Phe Glu Asp385 390
395 400 Val Thr Glu Lys Val Asn Leu Ser Tyr Thr Ser
Asn Gly Gly Tyr Thr 405 410
415 Leu Asn Leu Gly Asp Leu Asp Asn Ser Lys Asp Tyr Val Ile Lys Tyr
420 425 430 Glu Gly Glu
Tyr Asp Gln Asn Ala Lys Asp Leu Asn Phe Arg Thr His 435
440 445 Leu Ser Gly Tyr His Lys Tyr Tyr
Pro Tyr Tyr Pro Tyr Tyr Pro Tyr 450 455
460 Tyr Pro Val Gln Leu Thr Trp Asn Asn Gly Val Ala Phe
Tyr Ser Asn465 470 475
480 Asn Ala Lys Gly Asp Gly Lys Asp Lys Pro Asn Asp Pro Ile Ile Glu
485 490 495 Lys Ser Glu Pro
Ile Asp Leu Asp Ile Lys Ser Glu Pro Pro Val Glu 500
505 510 Lys His Glu Leu Thr Gly Thr Ile Glu
Glu Ser Asn Asp Ser Lys Pro 515 520
525 Ile Asp Phe Glu Tyr His Thr Ala Val Glu Gly Ala Glu Gly
His Ala 530 535 540
Glu Gly Ile Ile Glu Thr Glu Glu Asp Ser Ile His Val Asp Phe Glu545
550 555 560 Glu Ser Thr His Glu
Asn Ser Lys His His Ala Asp Val Val Glu Tyr 565
570 575 Glu Glu Asp Thr Asn Pro Gly Gly Gly Gln
Val Thr Thr Glu Ser Asn 580 585
590 Leu Val Glu Phe Asp Glu Glu Ser Thr Lys Gly Ile Val Thr Gly
Ala 595 600 605 Val
Ser Asp His Thr Thr Val Glu Asp Thr Lys Glu Tyr Thr Thr Glu 610
615 620 Ser Asn Leu Ile Glu Leu
Val Asp Glu Leu Pro Glu Glu His Gly Gln625 630
635 640 Ala Gln Gly Pro Ile Glu Glu Ile Thr Glu Asn
Asn His His Ile Ser 645 650
655 His Ser Gly Leu Gly Thr Glu Asn Gly His Gly Asn Tyr Gly Val Ile
660 665 670 Asp Glu Ile
Glu Glu Asn Ser His Val Asp Ile Lys Ser Glu Leu Gly 675
680 685 Tyr Glu Gly Gly Gln Asn Ser Gly
Asn Gln Ser Phe Glu Glu Asp Thr 690 695
700 Glu Glu Asp Lys Pro Lys Tyr Glu Gln Gly Gly Asn Ile
Val Asp Ile705 710 715
720 Asp Phe Asp Ser Val Pro Gln Ile His Gly Gln Asn Asn Gly Asn Gln
725 730 735 Ser Phe Glu Glu
Asp Thr Glu Glu Asp Lys Pro Lys Tyr Glu Gln Gly 740
745 750 Gly Asn Ile Ile Asp Ile Asp Phe Asp
Ser Val Pro Gln Ile His Gly 755 760
765 Phe Asn Lys His Asn Glu Ile Ile Glu Glu Asp Thr Asn Lys
Asp Lys 770 775 780
Pro Asn Tyr Gln Phe Gly Gly His Asn Ser Val Asp Phe Glu Glu Asp785
790 795 800 Thr Leu Pro Lys Val
Ser Gly Gln Asn Glu Gly Gln Gln Thr Ile Glu 805
810 815 Glu Asp Thr Thr Pro Pro Thr Pro Pro Thr
Pro Glu Val Pro Ser Glu 820 825
830 Pro Glu Thr Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu Pro
Gly 835 840 845 Glu
Pro Thr Pro Pro Lys Pro Glu Val Pro Ser Glu Pro Glu Thr Pro 850
855 860 Val Pro Pro Thr Pro Glu
Val Pro Ser Glu Pro Gly Lys Pro Val Pro865 870
875 880 Pro Ala Lys Glu Glu Pro Lys Lys Pro Ser Lys
Pro Val Glu Gln Gly 885 890
895 Lys Val Val Thr Pro Val Ile Glu Ile Asn Glu Lys Val Lys Ala Val
900 905 910 Ala Pro Thr
Lys Gln Lys Gln Ser Lys Lys Ser Glu Leu Pro Glu Thr 915
920 925 Gly Gly Glu Glu Ser Thr Asn Lys
Gly Met Leu Phe Gly Gly Leu Phe 930 935
940 Ser Ile Leu Gly Leu Val Leu Leu Arg Arg Asn Lys Lys
Asn Asn Lys945 950 955
960 Ala68578PRTStaphylococcus sp. 68Met Lys Phe Lys Ser Leu Ile Thr Thr
Thr Leu Ala Leu Gly Val Ile1 5 10
15 Ala Ser Thr Gly Ala Asn Phe Asn Thr Asn Glu Ala Ser Ala
Ala Ala 20 25 30
Lys Pro Leu Asp Lys Ser Ser Ser Thr Leu His His Gly His Ser Asn 35
40 45 Ile Gln Ile Pro Tyr
Thr Ile Thr Val Asn Gly Thr Ser Gln Asn Ile 50 55
60 Leu Ser Ser Leu Thr Phe Asn Lys Asn Gln
Asn Ile Ser Tyr Lys Asp65 70 75
80 Ile Glu Asn Lys Val Lys Ser Val Leu Tyr Phe Asn Arg Gly Ile
Ser 85 90 95 Asp
Ile Asp Leu Arg Leu Ser Lys Gln Ala Glu Tyr Thr Val His Phe
100 105 110 Lys Asn Gly Thr Lys
Arg Val Ile Asp Leu Lys Ser Gly Ile Tyr Thr 115
120 125 Ala Asp Leu Ile Asn Thr Ser Asp Ile
Lys Ala Ile Ser Val Asn Val 130 135
140 Asp Thr Lys Lys Gln Pro Lys Asp Lys Ala Lys Ala Asn
Val Gln Val145 150 155
160 Pro Tyr Thr Ile Thr Val Asn Gly Thr Ser Gln Asn Ile Leu Ser Asn
165 170 175 Leu Thr Phe Asn
Lys Asn Gln Asn Ile Ser Tyr Lys Asp Leu Glu Gly 180
185 190 Lys Val Lys Ser Val Leu Glu Ser Asn
Arg Gly Ile Thr Asp Val Asp 195 200
205 Leu Arg Leu Ser Lys Gln Ala Lys Tyr Thr Val Asn Phe Lys
Asn Gly 210 215 220
Thr Lys Lys Val Ile Asp Leu Lys Ser Gly Ile Tyr Thr Ala Asn Leu225
230 235 240 Ile Asn Ser Ser Asp
Ile Lys Ser Ile Asn Ile Asn Val Asp Thr Lys 245
250 255 Lys His Ile Glu Asn Lys Ala Lys Arg Asn
Tyr Gln Val Pro Tyr Ser 260 265
270 Ile Asn Leu Asn Gly Thr Ser Thr Asn Ile Leu Ser Asn Leu Ser
Phe 275 280 285 Ser
Asn Lys Pro Trp Thr Asn Tyr Lys Asn Leu Thr Ser Gln Ile Lys 290
295 300 Ser Val Leu Lys His Asp
Arg Gly Ile Ser Glu Gln Asp Leu Lys Tyr305 310
315 320 Ala Lys Lys Ala Tyr Tyr Thr Val Tyr Phe Lys
Asn Gly Gly Lys Arg 325 330
335 Ile Leu Gln Leu Asn Ser Lys Asn Tyr Thr Ala Asn Leu Val His Ala
340 345 350 Lys Asp Val
Lys Arg Ile Glu Ile Thr Val Lys Thr Gly Thr Lys Ala 355
360 365 Lys Ala Asp Arg Tyr Val Pro Tyr
Thr Ile Ala Val Asn Gly Thr Ser 370 375
380 Thr Pro Ile Leu Ser Lys Leu Lys Ile Ser Asn Lys Gln
Leu Ile Ser385 390 395
400 Tyr Lys Tyr Leu Asn Asp Lys Val Lys Ser Val Leu Lys Ser Glu Arg
405 410 415 Gly Ile Ser Asp
Leu Asp Leu Lys Phe Ala Lys Gln Ala Lys Tyr Thr 420
425 430 Val Tyr Phe Lys Asn Gly Lys Lys Gln
Val Val Asn Leu Lys Ser Asp 435 440
445 Ile Phe Thr Pro Asn Leu Phe Ser Ala Lys Asp Ile Lys Lys
Ile Asp 450 455 460
Ile Asp Val Lys Gln Tyr Thr Lys Ser Lys Lys Lys Ile Asn Lys Ser465
470 475 480 Asn Asn Val Lys Phe
Pro Val Thr Ile Asn Lys Phe Glu Asn Ile Val 485
490 495 Ser Asn Glu Phe Val Phe Tyr Asn Ala Ser
Lys Ile Thr Ile Asn Asp 500 505
510 Leu Ser Ile Lys Leu Lys Ser Ala Met Ala Asn Asp Gln Gly Ile
Thr 515 520 525 Lys
His Asp Ile Gly Leu Ala Glu Arg Ala Val Tyr Lys Val Tyr Phe 530
535 540 Lys Asn Gly Ser Ser Lys
Tyr Val Asp Leu Lys Thr Glu Tyr Lys Asp545 550
555 560 Glu Arg Val Phe Lys Ala Thr Asp Ile Lys Lys
Val Asp Ile Glu Leu 565 570
575 Lys Phe69995PRTStaphylococcus sp. 69Met Asn Asn Lys Lys Thr Ala
Thr Asn Arg Lys Gly Met Ile Pro Asn1 5 10
15 Arg Leu Asn Lys Phe Ser Ile Arg Lys Tyr Ser Val
Gly Thr Ala Ser 20 25 30
Ile Leu Val Gly Thr Thr Leu Ile Phe Gly Leu Ser Gly His Glu Ala
35 40 45 Lys Ala Ala Glu
His Thr Asn Gly Glu Leu Asn Gln Ser Lys Asn Glu 50 55
60 Thr Thr Ala Pro Ser Glu Asn Lys Thr
Thr Lys Lys Val Asp Ser Arg65 70 75
80 Gln Leu Lys Asp Asn Thr Gln Thr Ala Thr Ala Asp Gln Pro
Lys Val 85 90 95
Thr Met Ser Asp Ser Ala Thr Val Lys Glu Thr Ser Ser Asn Met Gln
100 105 110 Ser Pro Gln Asn Ala
Thr Ala Asn Gln Ser Thr Thr Lys Thr Ser Asn 115
120 125 Val Thr Thr Asn Asp Lys Ser Ser Thr
Thr Tyr Ser Asn Glu Thr Asp 130 135
140 Lys Ser Asn Leu Thr Gln Ala Lys Asp Val Ser Thr Thr
Pro Lys Thr145 150 155
160 Thr Thr Ile Lys Pro Arg Thr Leu Asn Arg Met Ala Val Asn Thr Val
165 170 175 Ala Ala Pro Gln
Gln Gly Thr Asn Val Asn Asp Lys Val His Phe Ser 180
185 190 Asn Ile Asp Ile Ala Ile Asp Lys Gly
His Val Asn Gln Thr Thr Gly 195 200
205 Lys Thr Glu Phe Trp Ala Thr Ser Ser Asp Val Leu Lys Leu
Lys Ala 210 215 220
Asn Tyr Thr Ile Asp Asp Ser Val Lys Glu Gly Asp Thr Phe Thr Phe225
230 235 240 Lys Tyr Gly Gln Tyr
Phe Arg Pro Gly Ser Val Arg Leu Pro Ser Gln 245
250 255 Thr Gln Asn Leu Tyr Asn Ala Gln Gly Asn
Ile Ile Ala Lys Gly Ile 260 265
270 Tyr Asp Ser Thr Thr Asn Thr Thr Thr Tyr Thr Phe Thr Asn Tyr
Val 275 280 285 Asp
Gln Tyr Thr Asn Val Arg Gly Ser Phe Glu Gln Val Ala Phe Ala 290
295 300 Lys Arg Lys Asn Ala Thr
Thr Asp Lys Thr Ala Tyr Lys Met Glu Val305 310
315 320 Thr Leu Gly Asn Asp Thr Tyr Ser Glu Glu Ile
Ile Val Asp Tyr Gly 325 330
335 Asn Lys Lys Ala Gln Pro Leu Ile Ser Ser Thr Asn Tyr Ile Asn Asn
340 345 350 Glu Asp Leu
Ser Arg Asn Met Thr Ala Tyr Val Asn Gln Pro Lys Asn 355
360 365 Thr Tyr Thr Lys Gln Thr Phe Val
Thr Asn Leu Thr Gly Tyr Lys Phe 370 375
380 Asn Pro Asn Ala Lys Asn Phe Lys Ile Tyr Glu Val Thr
Asp Gln Asn385 390 395
400 Gln Phe Val Asp Ser Phe Thr Pro Asp Thr Ser Lys Leu Lys Asp Val
405 410 415 Thr Asp Gln Phe
Asp Val Ile Tyr Ser Asn Asp Asn Lys Thr Ala Thr 420
425 430 Val Asp Leu Met Lys Gly Gln Thr Ser
Ser Asn Lys Gln Tyr Ile Ile 435 440
445 Gln Gln Val Ala Tyr Pro Asp Asn Ser Ser Thr Asp Asn Gly
Lys Ile 450 455 460
Asp Tyr Thr Leu Asp Thr Asp Lys Thr Lys Tyr Ser Trp Ser Asn Ser465
470 475 480 Tyr Ser Asn Val Asn
Gly Ser Ser Thr Ala Asn Gly Asp Gln Lys Lys 485
490 495 Tyr Asn Leu Gly Asp Tyr Val Trp Glu Asp
Thr Asn Lys Asp Gly Lys 500 505
510 Gln Asp Ala Asn Glu Lys Gly Ile Lys Gly Val Tyr Val Ile Leu
Lys 515 520 525 Asp
Ser Asn Gly Lys Glu Leu Asp Arg Thr Thr Thr Asp Glu Asn Gly 530
535 540 Lys Tyr Gln Phe Thr Gly
Leu Ser Asn Gly Thr Tyr Ser Val Glu Phe545 550
555 560 Ser Thr Pro Ala Gly Tyr Thr Pro Thr Thr Ala
Asn Val Gly Thr Asp 565 570
575 Asp Ala Val Asp Ser Asp Gly Leu Thr Thr Thr Gly Val Ile Lys Asp
580 585 590 Ala Asp Asn
Met Thr Leu Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr 595
600 605 Ser Leu Gly Asp Tyr Val Trp Tyr
Asp Ser Asn Lys Asp Gly Lys Gln 610 615
620 Asp Ser Thr Glu Lys Gly Ile Lys Gly Val Lys Val Thr
Leu Gln Asn625 630 635
640 Glu Lys Gly Glu Val Ile Gly Thr Thr Glu Thr Asp Glu Asn Gly Lys
645 650 655 Tyr Arg Phe Asp
Asn Leu Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu 660
665 670 Lys Pro Ala Gly Leu Thr Gln Thr Gly
Thr Asn Thr Thr Glu Asp Asp 675 680
685 Lys Asp Ala Asp Gly Gly Glu Val Asp Val Thr Ile Thr Asp
His Asp 690 695 700
Asp Phe Thr Leu Asp Asn Gly Tyr Tyr Glu Glu Glu Thr Ser Asp Ser705
710 715 720 Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 725
730 735 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser 740 745
750 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser 755 760 765 Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 770
775 780 Asp Ser Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser785 790
795 800 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser Asp Ser 805 810
815 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
820 825 830 Asp Ser Asp
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 835
840 845 Asp Ser Asp Ser Asp Ser Asp Ser
Asp Asn Asp Ser Asp Ser Asp Ser 850 855
860 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Ser865 870 875
880 Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser
885 890 895 Asp Ser Asp Ser
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 900
905 910 Asp Ser Asp Ser Asp Ser Asp Ser Asp
Ser Asp Asn Asp Ser Asp Ser 915 920
925 Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys His Thr Pro Ala
Lys Pro 930 935 940
Met Ser Thr Val Lys Asp Gln His Lys Thr Ala Lys Ala Leu Pro Glu945
950 955 960 Thr Gly Ser Glu Asn
Asn Asn Ser Asn Asn Gly Thr Leu Phe Gly Gly 965
970 975 Leu Phe Ala Ala Leu Gly Ser Leu Leu Leu
Phe Gly Arg Arg Lys Lys 980 985
990 Gln Asn Lys 995 70773PRTStaphylococcus sp. 70Glu Glu
Asn Ser Val Gln Asp Val Lys Asp Ser Asn Thr Asp Asp Glu1 5
10 15 Leu Ser Asp Ser Asn Asp Gln
Ser Ser Asp Glu Glu Lys Asn Asp Val 20 25
30 Ile Asn Asn Asn Gln Ser Ile Asn Thr Asp Asp Asn
Asn Gln Ile Ile 35 40 45
Lys Lys Glu Glu Thr Asn Asn Tyr Asp Gly Ile Glu Lys Arg Ser Glu
50 55 60 Asp Arg Thr
Glu Ser Thr Thr Asn Val Asp Glu Asn Glu Ala Thr Phe65 70
75 80 Leu Gln Lys Thr Pro Gln Asp Asn
Thr His Leu Thr Glu Glu Glu Val 85 90
95 Lys Glu Ser Ser Ser Val Glu Ser Ser Asn Ser Ser Ile
Asp Thr Ala 100 105 110
Gln Gln Pro Ser His Thr Thr Ile Asn Arg Glu Glu Ser Val Gln Thr
115 120 125 Ser Asp Asn Val
Glu Asp Ser His Val Ser Asp Phe Ala Asn Ser Lys 130
135 140 Ile Lys Glu Ser Asn Thr Glu Ser
Gly Lys Glu Glu Asn Thr Ile Glu145 150
155 160 Gln Pro Asn Lys Val Lys Glu Asp Ser Thr Thr Ser
Gln Pro Ser Gly 165 170
175 Tyr Thr Asn Ile Asp Glu Lys Ile Ser Asn Gln Asp Glu Leu Leu Asn
180 185 190 Leu Pro Ile
Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu Ser Thr Thr 195
200 205 Ser Ala Gln Pro Ser Ile Lys Arg
Val Thr Val Asn Gln Leu Ala Ala 210 215
220 Glu Gln Gly Ser Asn Val Asn His Leu Ile Lys Val Thr
Asp Gln Ser225 230 235
240 Ile Thr Glu Gly Tyr Asp Asp Ser Glu Gly Val Ile Lys Ala His Asp
245 250 255 Ala Glu Asn Leu
Ile Tyr Asp Val Thr Phe Glu Val Asp Asp Lys Val 260
265 270 Lys Ser Gly Asp Thr Met Thr Val Asp
Ile Asp Lys Asn Thr Val Pro 275 280
285 Ser Asp Leu Thr Asp Ser Phe Thr Ile Pro Lys Ile Lys Asp
Asn Ser 290 295 300
Gly Glu Ile Ile Ala Thr Gly Thr Tyr Asp Asn Lys Asn Lys Gln Ile305
310 315 320 Thr Tyr Thr Phe Thr
Asp Tyr Val Asp Lys Tyr Glu Asn Ile Lys Ala 325
330 335 His Leu Lys Leu Thr Ser Tyr Ile Asp Lys
Ser Lys Val Pro Asn Asn 340 345
350 Asn Thr Lys Leu Asp Val Glu Tyr Lys Thr Ala Leu Ser Ser Val
Asn 355 360 365 Lys
Thr Ile Thr Val Glu Tyr Gln Arg Pro Asn Glu Asn Arg Thr Ala 370
375 380 Asn Leu Gln Ser Met Phe
Thr Asn Ile Asp Thr Lys Asn His Thr Val385 390
395 400 Glu Gln Thr Ile Tyr Ile Asn Pro Leu Arg Tyr
Ser Ala Lys Glu Thr 405 410
415 Asn Val Asn Ile Ser Gly Asn Gly Asp Glu Gly Ser Thr Ile Ile Asp
420 425 430 Asp Ser Thr
Ile Ile Lys Val Tyr Lys Val Gly Asp Asn Gln Asn Leu 435
440 445 Pro Asp Ser Asn Arg Ile Tyr Asp
Tyr Ser Glu Tyr Glu Asp Val Thr 450 455
460 Asn Asp Asp Tyr Ala Gln Leu Gly Asn Asn Asn Asp Val
Asn Ile Asn465 470 475
480 Phe Gly Asn Ile Asp Ser Pro Tyr Ile Ile Lys Val Ile Ser Lys Tyr
485 490 495 Asp Pro Asn Lys
Asp Asp Tyr Thr Thr Ile Gln Gln Thr Val Thr Met 500
505 510 Gln Thr Thr Ile Asn Glu Tyr Thr Gly
Glu Phe Arg Thr Ala Ser Tyr 515 520
525 Asp Asn Thr Ile Ala Phe Ser Thr Ser Ser Gly Gln Gly Gln
Gly Asp 530 535 540
Leu Pro Pro Glu Lys Thr Tyr Lys Ile Gly Asp Tyr Val Trp Glu Asp545
550 555 560 Val Asp Lys Asp Gly
Ile Gln Asn Thr Asn Asp Asn Glu Lys Pro Leu 565
570 575 Ser Asn Val Leu Val Thr Leu Thr Tyr Pro
Asp Gly Thr Ser Lys Ser 580 585
590 Val Arg Thr Asp Glu Asp Gly Lys Tyr Gln Phe Asp Gly Leu Lys
Asn 595 600 605 Gly
Leu Thr Tyr Lys Ile Thr Phe Glu Thr Pro Glu Gly Tyr Thr Pro 610
615 620 Thr Leu Lys His Ser Gly
Thr Asn Pro Ala Leu Asp Ser Glu Gly Asn625 630
635 640 Ser Val Trp Val Thr Ile Asn Gly Gln Asp Asp
Met Thr Ile Asp Ser 645 650
655 Gly Phe Tyr Gln Thr Pro Lys Tyr Ser Leu Gly Asn Tyr Val Trp Tyr
660 665 670 Asp Thr Asn
Lys Asp Gly Ile Gln Gly Asp Asp Glu Lys Gly Ile Ser 675
680 685 Gly Val Lys Val Thr Leu Lys Asp
Glu Asn Gly Asn Ile Ile Ser Thr 690 695
700 Thr Thr Thr Asp Glu Asn Gly Lys Tyr Gln Phe Asp Asn
Leu Asn Ser705 710 715
720 Gly Asn Tyr Ile Val His Phe Asp Lys Pro Ser Gly Met Thr Gln Thr
725 730 735 Thr Thr Asp Ser
Gly Asp Asp Asp Glu Gln Asp Ala Asp Gly Glu Glu 740
745 750 Val His Val Thr Ile Thr Asp His Asp
Asp Phe Ser Ile Asp Asn Gly 755 760
765 Tyr Tyr Asp Asp Glu 770
712886DNAStaphylococcus sp. 71gtgaaaagca atcttagata cggcataaga aaacacaaat
tgggagcggc ctcagtattc 60ttaggaacaa tgatcgttgt tggaatggga caagaaaaag
aagctgcagc atcggaacaa 120aacaatacta cagtagagga aagtgggagt tcagctactg
aaagtaaagc aagcgaaaca 180caaacaacta caaataacgt taatacaata gatgaaacac
aatcatacag cgcgacatca 240actgagcaac catcaaaatc aactcaagta acaacagaag
aagcaccaac aactgtgcaa 300gcaccaaaag tagaaaccga aatgaaatca caagaagatt
taccatcaga aaaagttgct 360gataaggaaa ctacaggaac tcaagttgac atagctcaac
caagtaacgt ctcagaaatt 420aaaccaagaa tgaaaagatc agctgacgtt acagcagttt
cagagaaaga agtagcggaa 480gaagctaaag cgacaggtac agatgtaaca aataaagtgg
aagttactga aagctcttta 540gaaggacata ataaagattc gaatattgtt aatccgcata
atgctcaaag agtaacttta 600aaatacaaat ggaaatttgg agaaggaatt aaggcaggag
attattttga tttcacatta 660agtgataatg ttgaaacaca tggtatatca acactgcgta
aagttccgga gataaaaagt 720tcaacagaag ataaagttat ggcaaatggt caagttataa
atgaacgtac aattcgctat 780acatttactg attatataaa taacaaaaaa gatttaactg
ctgaattaaa cttaaaccta 840ttcattgacc caacaacagt gacaaagcaa gggagtcaaa
aagttgaagt aacactaggt 900caaaataaag tctcaaaaga atttgatatc aaatatttag
acggcgttaa agatagaatg 960ggtgttactg ttaatggtcg tattgatact ttgaataaag
aagagggtaa atttagccat 1020tttgcatatg tgaagcctaa caaccagtcg ttaacttctg
tcacagtaac tggtcaagta 1080acatctggat ataaacaaag tgctaataat ccaacagtca
aagtatataa acacattggt 1140tcagatgaat tagctgaaag tgtttatgca aagcttgatg
ataccagtaa atttgaagat 1200gtgactgaaa aagtaaatct atcttacaca agtaatggtg
ggtacacatt gaaccttggc 1260gatttagata attcgaaaga ctatgtaatt aaatatgaag
gtgaatatga tcaaaatgct 1320aaggatctaa atttccgaac acatctttca ggatatcata
aatactaccc atactatcct 1380tattacccgt attatccagt tcaattaact tggaacaacg
gtgttgcatt ttactctaat 1440aatgctaaag gcgatggtaa agataaacca aatgatccta
tcattgagaa gagtgaacca 1500attgatttag acattaaatc agagccacca gtggagaagc
atgaattgac tggtacaatc 1560gaagaaagta acgattctaa gccaattgat tttgaatatc
atacagctgt tgaaggtgca 1620gaaggtcatg cagaaggtat tattgaaact gaagaagatt
ctattcatgt ggattttgaa 1680gaatctacac atgaaaattc aaaacatcac gctgatgttg
ttgaatatga agaggataca 1740aacccaggtg gtggccaagt aacaactgag tctaacttag
ttgaatttga cgaagagtct 1800acaaaaggta ttgtaactgg cgcagtgagc gaccatacaa
cagttgaaga tacgaaagaa 1860tatacaactg aaagtaatct gattgaatta gtggatgaat
tacctgaaga acatggtcaa 1920gcacaagggc caatcgagga aattactgaa aacaatcatc
atatttctca ttctggttta 1980ggaactgaaa atggtcacgg taattatggc gtgattgatg
aaatcgaaga aaatagccac 2040gttgatatta agagtgaatt aggttatgaa ggtggccaaa
atagcggtaa tcagtcattc 2100gaggaagaca cagaagaaga taaacctaaa tatgaacaag
gtggtaatat cgtagatatc 2160gatttcgaca gtgtacctca aattcatggt caaaataatg
gtaaccagtc attcgaggaa 2220gacacagaag aagacaagcc taagtatgaa caaggtggta
acatcattga tatcgacttc 2280gacagtgtgc cacaaattca tggattcaat aagcataatg
aaattattga agaagataca 2340aacaaagata aacctaatta tcaatttggt ggacacaaca
gtgttgattt tgaagaagat 2400acacttccaa aagtaagtgg tcaaaatgaa ggtcaacaaa
cgattgaaga agatacaacg 2460ccgccaacac cgccaacacc agaggtacca agtgagccgg
aaacaccaac accaccaaca 2520ccagaagtac cgagtgagcc aggcgaacca acgccaccaa
aaccggaagt accaagtgag 2580ccggaaacac cagtaccacc aacaccagag gtaccatctg
aacctggtaa accagtacca 2640cctgctaaag aagaacctaa aaaaccttct aaaccagtgg
aacaaggtaa ggtagtaaca 2700cctgttattg aaatcaatga aaaggttaaa gcagtggcac
caactaaaca aaaacaatct 2760aagaaatctg aactacctga aacaggtgga gaagaatcaa
caaacaaagg tatgttgttc 2820ggcggattat tcagcattct aggtttagta ttattacgca
gaaataaaaa gaataacaaa 2880gcataa
2886721737DNAStaphylococcus sp. 72atgaaattta
agtcattgat tacaacaaca ttagcattag gcgttatagc atcaacagga 60gcaaacttta
atactaacga agcatctgcc gcagctaagc cattagataa atcatcaagt 120acattacacc
atggacattc taacatccag attccatata caattactgt gaacggtaca 180agccaaaaca
ttttatcaag cttaacattt aataagaatc aaaatattag ttataaagat 240atagagaata
aagttaaatc agttttatac tttaatagag gtattagtga tatcgattta 300agactttcaa
agcaagcgga atatacggtt cattttaaaa atggaacaaa aagagttatc 360gatttgaaat
caggtatcta cacagctgac ttaatcaata caagtgacat taaagctatc 420agtgttaacg
tagatactaa aaagcaacct aaagataaag ctaaagcaaa tgttcaagtg 480ccatatacaa
tcacagtgaa cggcacaagc caaaacattt tatcaaacct aacatttaat 540aaaaatcaaa
atattagtta caaagattta gagggtaaag ttaaatcagt tttagaatca 600aatagaggta
ttactgatgt tgatttaaga ctttcgaagc aagcgaaata tacagttaat 660tttaaaaatg
gaacgaagaa agttatcgat ttgaaatcag gtatttacac agcgaattta 720atcaattcaa
gtgatattaa aagtatcaat attaacgtag atacaaaaaa acatatcgaa 780aataaagcta
aaagaaacta tcaagttcca tattcaatta atctaaatgg tacatctaca 840aacattttat
cgaatctttc attttcaaat aaaccttgga caaattacaa aaatttaact 900agtcaaataa
aatcagtact gaagcatgat agaggtatta gtgaacaaga tttaaaatat 960gctaagaaag
cttattatac tgtttatttt aaaaatggtg gtaaaagaat cttacagtta 1020aattcaaaaa
attacacagc aaacttagtt catgcgaaag atgttaagag aattgaaatt 1080actgttaaaa
caggaactaa agcgaaagca gacagatatg taccatacac aattgcagta 1140aatggcacat
caacaccaat tttatcaaaa ctaaaaattt cgaataaaca attaattagt 1200tacaaatatt
taaacgacaa agtgaaatct gtattaaaaa gtgaaagagg tatcagtgat 1260cttgacttaa
aatttgcgaa acaagcaaaa tatacagtat atttcaaaaa tggaaagaaa 1320caagtagtga
atttaaaatc agacatcttt acacctaatt tatttagtgc caaagatatt 1380aaaaagattg
atattgatgt aaaacaatac actaaatcaa aaaaaaaaat aaataaatct 1440aataatgtga
aattcccagt aacaataaat aaatttgaaa acatagtttc aaatgaattt 1500gtgttctata
atgcaagcaa aattacaatt aatgatttaa gtataaaact taaatcagca 1560atggcaaatg
atcaagggat aactaaacat gacataggac ttgctgaacg cgcagtgtat 1620aaagtgtatt
ttaaaaatgg ttcgtcaaaa tatgtagact taaaaactga gtataaagat 1680gaaagagtat
ttaaagcaac tgacattaaa aaggtagata ttgaacttaa attctaa
1737732988DNAStaphylococcus sp. 73atgaataata aaaagacagc aacaaataga
aaaggcatga taccaaatcg attaaacaaa 60ttttcgataa gaaagtattc tgtaggtact
gcttcaattt tagtagggac aacattgatt 120tttgggttaa gtggtcatga agctaaagcg
gcagaacata cgaatggaga attaaatcaa 180tcaaaaaatg aaacgacagc cccaagtgag
aataaaacaa ctaaaaaagt tgatagtcgt 240caactaaaag acaatacgca aactgcaact
gcagatcagc ctaaagtgac aatgagtgat 300agtgcaacag ttaaagaaac tagtagtaac
atgcaatcac cacaaaacgc tacagctaat 360caatctacta caaaaactag caatgtaaca
acaaatgata aatcatcaac tacatatagt 420aatgaaactg ataaaagtaa tttaacacaa
gcaaaagatg tttcaactac acctaaaaca 480acgactatta aaccaagaac tttaaatcgc
atggcagtga atactgttgc agctccacaa 540caaggaacaa atgttaatga taaagtacat
ttttcaaata ttgacattgc gattgataaa 600ggacatgtta atcagactac tggtaaaact
gaattttggg caacttcaag tgatgtttta 660aaattaaaag caaattacac aatcgatgat
tctgttaaag agggcgatac atttactttt 720aaatatggtc aatatttccg tccaggatca
gtaagattac cttcacaaac tcaaaattta 780tataatgccc aaggtaatat tattgcaaaa
ggtatttatg atagtacaac aaacacaaca 840acatatactt ttacgaacta tgtagatcaa
tatacaaatg ttagaggtag ctttgaacaa 900gttgcatttg cgaaacgtaa aaatgcaaca
actgataaaa cagcttataa aatggaagta 960actttaggta atgatacata tagcgaagaa
atcattgtcg attatggtaa taaaaaagca 1020caaccgctta tttcaagtac aaactatatt
aacaatgaag atttatcgcg taatatgact 1080gcatatgtaa atcaacctaa aaatacatat
actaaacaaa cgtttgttac taatttaact 1140ggatataaat ttaatccaaa tgcaaaaaac
ttcaaaattt acgaagtgac agatcaaaat 1200caatttgtgg atagtttcac ccctgatact
tcaaaactta aagatgttac tgatcaattc 1260gatgttattt atagtaatga taataaaaca
gctacagtcg atttaatgaa aggccaaaca 1320agcagcaata aacaatacat cattcaacaa
gttgcttatc cagataatag ttcaacagat 1380aatggaaaaa ttgattatac tttagacact
gacaaaacta aatatagttg gtcaaatagt 1440tattcaaatg tgaatggctc atcaactgct
aatggcgacc aaaagaaata taatctaggt 1500gactatgtat gggaagatac aaataaagat
ggtaaacaag atgccaatga aaaagggatt 1560aaaggtgttt atgtcattct taaagatagt
aacggtaaag aattagatcg tacgacaaca 1620gatgaaaatg gtaaatatca gttcactggt
ttaagcaatg gaacttatag tgtagagttt 1680tcaacaccag ccggttatac accgacaact
gcaaatgtag gtacagatga tgctgtagat 1740tctgatggac taactacaac aggtgtcatt
aaagacgctg acaacatgac attagatagt 1800ggattctaca aaacaccaaa atatagttta
ggtgattatg tttggtacga cagtaataaa 1860gatggtaaac aagattcgac tgaaaaagga
attaaaggtg ttaaagttac tttgcaaaac 1920gaaaaaggcg aagtaattgg tacaactgaa
acagatgaaa atggtaaata ccgctttgat 1980aatttagata gtggtaaata caaagttatc
tttgaaaaac ctgctggctt aactcaaaca 2040ggtacaaata caactgaaga tgataaagat
gccgatggtg gcgaagttga tgtaacaatt 2100acggatcatg atgatttcac acttgataat
ggctactacg aagaagaaac atcagatagc 2160gactcagatt ctgacagcga ttcagactca
gatagcgact cagattcaga tagcgactca 2220gattcagaca gcgattcaga cagcgactca
gactcagata gcgattcaga ttcagacagc 2280gactcagact cagacagcga ttcagactcg
gatagcgact cagactcaga tagcgactca 2340gattcggata gcgactcaga ctcagatagc
gattcagatt cagatagcga ttcggactca 2400gacagtgatt cagattcaga ctcagatagc
gactcagatt ctgacagcga ttcagactca 2460gacagcgact cagactcaga cagtgattca
gattcagaca gcgactcaga ttcagatagc 2520gactcagact cagatagcga ctcagattca
gatagcgatt cggactcaga caacgactca 2580gattcagata gcgattcaga ttcagatagc
gactcagatt cggacagcga ttcagactca 2640gatagcgatt cagactcaga cagcgattca
gattcagata gcgactcaga ctcagatagc 2700gactcagact cggatagcga ttcagattca
gacagcgact cagattcaga tagcgattcg 2760gactcagaca acgactcaga ttcagatagc
gattcagatt cagatgcagg taaacatact 2820ccggctaaac caatgagtac ggttaaagat
cagcataaaa cagctaaagc attaccagaa 2880acaggtagtg aaaataataa ttcaaataat
ggcacattat tcggtggatt attcgcggca 2940ttaggatcat tattgttatt cggtcgtcgt
aaaaaacaaa ataaataa 2988742319DNAStaphylococcus sp.
74gaggagaatt cagtacaaga cgttaaagat tcgaatacgg atgatgaatt atcagacagc
60aatgatcagt ctagtgatga agaaaagaat gatgtgatca ataataatca gtcaataaac
120accgacgata ataaccaaat aattaaaaaa gaagaaacga ataactacga tggcatagaa
180aaacgctcag aagatagaac agagtcaaca acaaatgtag atgaaaacga agcaacattt
240ttacaaaaga cccctcaaga taatactcat cttacagaag aagaggtaaa agaatcctca
300tcagtcgaat cctcaaattc atcaattgat actgcccaac aaccatctca cacaacaata
360aatagagaag aatctgttca aacaagtgat aatgtagaag attcacacgt atcagatttt
420gctaactcta aaataaaaga gagtaacact gaatctggta aagaagagaa tactatagag
480caacctaata aagtaaaaga agattcaaca acaagtcagc cgtctggcta tacaaatata
540gatgaaaaaa tttcaaatca agatgagtta ttaaatttac caataaatga atatgaaaat
600aaggctagac cattatctac aacatctgcc caaccatcga ttaaacgtgt aaccgtaaat
660caattagcgg cggaacaagg ttcgaatgtt aatcatttaa ttaaagttac tgatcaaagt
720attactgaag gatatgatga tagtgaaggt gttattaaag cacatgatgc tgaaaactta
780atctatgatg taacttttga agtagatgat aaggtgaaat ctggtgatac gatgacagtg
840gatatagata agaatacagt tccatcagat ttaaccgata gctttacaat accaaaaata
900aaagataatt ctggagaaat catcgctaca ggtacttatg ataacaaaaa taaacaaatc
960acctatactt ttacagatta tgtagataag tatgaaaata ttaaagcaca ccttaaatta
1020acgtcataca ttgataaatc aaaggttcca aataataata ccaagttaga tgtagaatat
1080aaaacggccc tttcatcagt aaataaaaca attacggttg aatatcaaag acctaacgaa
1140aatcggactg ctaaccttca aagtatgttt acaaacatag atacgaaaaa tcatacagtt
1200gagcaaacga tttatattaa ccctcttcgt tattcagcca aggaaacaaa tgtaaatatt
1260tcagggaatg gtgatgaagg ttcaacaatt atagacgata gcacaataat taaagtttat
1320aaggttggag ataatcaaaa tttaccagat agtaacagaa tttatgatta cagtgaatat
1380gaagatgtca caaatgatga ttatgcccaa ttaggaaata ataatgatgt gaatattaat
1440tttggtaata tagattcacc atatattatt aaagttatta gtaaatatga ccctaataag
1500gatgattaca cgactataca gcaaactgtg acaatgcaga cgactataaa tgagtatact
1560ggtgagttta gaacagcatc ctatgataat acaattgctt tctctacaag ttcaggtcaa
1620ggacaaggtg acttgcctcc tgaaaaaact tataaaatcg gagattacgt atgggaagat
1680gtagataaag atggtattca aaatacaaat gataatgaaa aaccgcttag taatgtattg
1740gtaactttga cgtatcctga tggaacttca aaatcagtca gaacagatga agatgggaaa
1800tatcaatttg atggattgaa aaacggattg acttataaaa ttacattcga aacacctgaa
1860ggatatacgc cgacgcttaa acattcagga acaaatcctg cactagactc agaaggtaat
1920tctgtatggg taactattaa tggacaagac gatatgacga ttgatagtgg attttatcaa
1980acacctaaat acagcttagg gaactatgta tggtatgaca ctaataaaga tggtattcaa
2040ggtgatgatg aaaaaggaat ctctggagtt aaagtgacgt taaaagatga aaacggaaat
2100atcattagta caactacaac cgatgaaaat ggaaagtatc aatttgataa tttaaatagt
2160ggtaattata ttgttcattt tgataaacct tcaggtatga ctcaaacaac aacagattct
2220ggtgatgatg acgaacagga tgctgatggg gaagaagttc atgtaacaat tactgatcat
2280gatgacttta gtatagataa cggatactat gatgacgaa
231975774PRTStaphylococcus sp. 75Met Glu Glu Asn Ser Val Gln Asp Val Lys
Asp Ser Asn Thr Asp Asp1 5 10
15 Glu Leu Ser Asp Ser Asn Asp Gln Ser Ser Asp Glu Glu Lys Asn
Asp 20 25 30 Val
Ile Asn Asn Asn Gln Ser Ile Asn Thr Asp Asp Asn Asn Gln Ile 35
40 45 Ile Lys Lys Glu Glu Thr
Asn Asn Tyr Asp Gly Ile Glu Lys Arg Ser 50 55
60 Glu Asp Arg Thr Glu Ser Thr Thr Asn Val Asp
Glu Asn Glu Ala Thr65 70 75
80 Phe Leu Gln Lys Thr Pro Gln Asp Asn Thr His Leu Thr Glu Glu Glu
85 90 95 Val Lys Glu
Ser Ser Ser Val Glu Ser Ser Asn Ser Ser Ile Asp Thr 100
105 110 Ala Gln Gln Pro Ser His Thr Thr
Ile Asn Arg Glu Glu Ser Val Gln 115 120
125 Thr Ser Asp Asn Val Glu Asp Ser His Val Ser Asp Phe
Ala Asn Ser 130 135 140
Lys Ile Lys Glu Ser Asn Thr Glu Ser Gly Lys Glu Glu Asn Thr Ile145
150 155 160 Glu Gln Pro Asn Lys
Val Lys Glu Asp Ser Thr Thr Ser Gln Pro Ser 165
170 175 Gly Tyr Thr Asn Ile Asp Glu Lys Ile Ser
Asn Gln Asp Glu Leu Leu 180 185
190 Asn Leu Pro Ile Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu Ser
Thr 195 200 205 Thr
Ser Ala Gln Pro Ser Ile Lys Arg Val Thr Val Asn Gln Leu Ala 210
215 220 Ala Glu Gln Gly Ser Asn
Val Asn His Leu Ile Lys Val Thr Asp Gln225 230
235 240 Ser Ile Thr Glu Gly Tyr Asp Asp Ser Glu Gly
Val Ile Lys Ala His 245 250
255 Asp Ala Glu Asn Leu Ile Tyr Asp Val Thr Phe Glu Val Asp Asp Lys
260 265 270 Val Lys Ser
Gly Asp Thr Met Thr Val Asp Ile Asp Lys Asn Thr Val 275
280 285 Pro Ser Asp Leu Thr Asp Ser Phe
Thr Ile Pro Lys Ile Lys Asp Asn 290 295
300 Ser Gly Glu Ile Ile Ala Thr Gly Thr Tyr Asp Asn Lys
Asn Lys Gln305 310 315
320 Ile Thr Tyr Thr Phe Thr Asp Tyr Val Asp Lys Tyr Glu Asn Ile Lys
325 330 335 Ala His Leu Lys
Leu Thr Ser Tyr Ile Asp Lys Ser Lys Val Pro Asn 340
345 350 Asn Asn Thr Lys Leu Asp Val Glu Tyr
Lys Thr Ala Leu Ser Ser Val 355 360
365 Asn Lys Thr Ile Thr Val Glu Tyr Gln Arg Pro Asn Glu Asn
Arg Thr 370 375 380
Ala Asn Leu Gln Ser Met Phe Thr Asn Ile Asp Thr Lys Asn His Thr385
390 395 400 Val Glu Gln Thr Ile
Tyr Ile Asn Pro Leu Arg Tyr Ser Ala Lys Glu 405
410 415 Thr Asn Val Asn Ile Ser Gly Asn Gly Asp
Glu Gly Ser Thr Ile Ile 420 425
430 Asp Asp Ser Thr Ile Ile Lys Val Tyr Lys Val Gly Asp Asn Gln
Asn 435 440 445 Leu
Pro Asp Ser Asn Arg Ile Tyr Asp Tyr Ser Glu Tyr Glu Asp Val 450
455 460 Thr Asn Asp Asp Tyr Ala
Gln Leu Gly Asn Asn Asn Asp Val Asn Ile465 470
475 480 Asn Phe Gly Asn Ile Asp Ser Pro Tyr Ile Ile
Lys Val Ile Ser Lys 485 490
495 Tyr Asp Pro Asn Lys Asp Asp Tyr Thr Thr Ile Gln Gln Thr Val Thr
500 505 510 Met Gln Thr
Thr Ile Asn Glu Tyr Thr Gly Glu Phe Arg Thr Ala Ser 515
520 525 Tyr Asp Asn Thr Ile Ala Phe Ser
Thr Ser Ser Gly Gln Gly Gln Gly 530 535
540 Asp Leu Pro Pro Glu Lys Thr Tyr Lys Ile Gly Asp Tyr
Val Trp Glu545 550 555
560 Asp Val Asp Lys Asp Gly Ile Gln Asn Thr Asn Asp Asn Glu Lys Pro
565 570 575 Leu Ser Asn Val
Leu Val Thr Leu Thr Tyr Pro Asp Gly Thr Ser Lys 580
585 590 Ser Val Arg Thr Asp Glu Asp Gly Lys
Tyr Gln Phe Asp Gly Leu Lys 595 600
605 Asn Gly Leu Thr Tyr Lys Ile Thr Phe Glu Thr Pro Glu Gly
Tyr Thr 610 615 620
Pro Thr Leu Lys His Ser Gly Thr Asn Pro Ala Leu Asp Ser Glu Gly625
630 635 640 Asn Ser Val Trp Val
Thr Ile Asn Gly Gln Asp Asp Met Thr Ile Asp 645
650 655 Ser Gly Phe Tyr Gln Thr Pro Lys Tyr Ser
Leu Gly Asn Tyr Val Trp 660 665
670 Tyr Asp Thr Asn Lys Asp Gly Ile Gln Gly Asp Asp Glu Lys Gly
Ile 675 680 685 Ser
Gly Val Lys Val Thr Leu Lys Asp Glu Asn Gly Asn Ile Ile Ser 690
695 700 Thr Thr Thr Thr Asp Glu
Asn Gly Lys Tyr Gln Phe Asp Asn Leu Asn705 710
715 720 Ser Gly Asn Tyr Ile Val His Phe Asp Lys Pro
Ser Gly Met Thr Gln 725 730
735 Thr Thr Thr Asp Ser Gly Asp Asp Asp Glu Gln Asp Ala Asp Gly Glu
740 745 750 Glu Val His
Val Thr Ile Thr Asp His Asp Asp Phe Ser Ile Asp Asn 755
760 765 Gly Tyr Tyr Asp Asp Glu 770
76128PRTStaphylococcus sp. 76Met Asp Val Asn Thr Val Asn
Gln Lys Ala Ala Ser Val Lys Ser Thr1 5 10
15 Lys Asp Ala Leu Asp Gly Gln Gln Asn Leu Gln Arg
Ala Lys Thr Glu 20 25 30
Ala Thr Asn Ala Ile Thr His Ala Ser Asp Leu Asn Gln Ala Gln Lys
35 40 45 Asn Ala Leu Thr
Gln Gln Val Asn Ser Ala Gln Asn Val His Ala Val 50 55
60 Asn Asp Ile Lys Gln Thr Thr Gln Ser
Leu Asn Thr Ala Met Thr Gly65 70 75
80 Leu Lys Arg Gly Val Ala Asn His Asn Gln Val Val Gln Ser
Asp Asn 85 90 95
Tyr Val Asn Ala Asp Thr Asn Lys Lys Asn Asp Tyr Asn Asn Ala Tyr
100 105 110 Asn His Ala Asn Asp
Ile Ile Asn Gly Asn Ala Gln His Pro Val Ile 115
120 125 776PRTStaphylococcus sp. 77Thr Val
Asn Gln Lys Ala1 5 786PRTStaphylococcus sp. 78Lys Ser
Thr Lys Asp Ala1 5 7913PRTStaphylococcus sp. 79Asp Gly
Gln Gln Asn Leu Gln Arg Ala Lys Thr Glu Ala1 5
10 8010PRTStaphylococcus sp. 80Asp Leu Asn Gln Ala Gln
Lys Asn Ala Leu1 5 10
819PRTStaphylococcus sp. 81Asp Ile Lys Gln Thr Thr Gln Ser Leu1
5 8213PRTStaphylococcus sp. 82Ala Asp Thr Asn Lys
Lys Asn Asp Tyr Asn Asn Ala Tyr1 5 10
837PRTStaphylococcus sp. 83Asp Ile Ile Asn Gly Asn Ala1
5 84128PRTStaphylococcus sp. 84Met Asp Val Asn Thr Val Asn
Gln Lys Ala Ala Ser Val Lys Ser Thr1 5 10
15 Lys Asp Ala Leu Asp Gly Gln Gln Asn Leu Gln Arg
Ala Lys Thr Glu 20 25 30
Ala Thr Asn Ala Ile Thr His Ala Ser Asp Leu Asn Gln Ala Gln Lys
35 40 45 Asn Ala Leu Thr
Gln Gln Val Asn Ser Ala Gln Asn Val His Ala Val 50 55
60 Asn Asp Ile Lys Gln Thr Thr Gln Ser
Leu Asn Thr Ala Met Thr Gly65 70 75
80 Leu Lys Arg Gly Val Ala Asn His Asn Gln Val Val Gln Ser
Asp Asn 85 90 95
Tyr Val Asn Ala Asp Thr Asn Lys Lys Asn Asp Tyr Asn Asn Ala Tyr
100 105 110 Asn His Ala Asn Asp
Ile Ile Asn Gly Asn Ala Gln His Pro Val Ile 115
120 125 859PRTStaphylococcus sp. 85Met Asp
Val Asn Thr Val Asn Gln Lys1 5
869PRTStaphylococcus sp. 86Val Asn Thr Val Asn Gln Lys Ala Ala1
5 879PRTStaphylococcus sp. 87Val Asn Gln Lys Ala Ala
Ser Val Lys1 5 889PRTStaphylococcus sp.
88Leu Gln Arg Ala Lys Thr Glu Ala Thr1 5
899PRTStaphylococcus sp. 89Ile Thr His Ala Ser Asp Leu Asn Gln1
5 909PRTStaphylococcus sp. 90Leu Asn Gln Ala Gln Lys
Asn Ala Leu1 5 919PRTStaphylococcus sp.
91Leu Thr Gln Gln Val Asn Ser Ala Gln1 5
929PRTStaphylococcus sp. 92Val Asn Ser Ala Gln Asn Val His Ala1
5 939PRTStaphylococcus sp. 93Val His Ala Val Asn Asp
Ile Lys Gln1 5 949PRTStaphylococcus sp.
94Val Asn Asp Ile Lys Gln Thr Thr Gln1 5
959PRTStaphylococcus sp. 95Ile Lys Gln Thr Thr Gln Ser Leu Asn1
5 969PRTStaphylococcus sp. 96Leu Asn Thr Ala Met Thr
Gly Leu Lys1 5 979PRTStaphylococcus sp.
97Met Thr Gly Leu Lys Arg Gly Val Ala1 5
989PRTStaphylococcus sp. 98Leu Lys Arg Gly Val Ala Asn His Asn1
5 999PRTStaphylococcus sp. 99Val Ala Asn His Asn Gln
Val Val Gln1 5 1009PRTStaphylococcus sp.
100Val Val Gln Ser Asp Asn Tyr Val Asn1 5
1019PRTStaphylococcus sp. 101Val Gln Ser Asp Asn Tyr Val Asn Ala1
5 1029PRTStaphylococcus sp. 102Tyr Val Asn Ala Asp
Thr Asn Lys Lys1 5 1039PRTStaphylococcus
sp. 103Val Asn Ala Asp Thr Asn Lys Lys Asn1 5
1049PRTStaphylococcus sp. 104Tyr Asn Asn Ala Tyr Asn His Ala Asn1
5 1059PRTStaphylococcus sp. 105Tyr Asn His Ala
Asn Asp Ile Ile Asn1 5
1069PRTStaphylococcus sp. 106Ile Ile Asn Gly Asn Ala Gln His Pro1
5 1079PRTStaphylococcus sp. 107Ile Asn Gly Asn Ala
Gln His Pro Val1 5 10852PRTStaphylococcus
sp. 108Gln Thr Thr Gln Asn Asn Tyr Val Thr Asp Gln Gln Lys Ala Phe Tyr1
5 10 15 Gln Val Leu
His Leu Lys Gly Ile Thr Glu Glu Gln Arg Asn Gln Tyr 20
25 30 Ile Lys Thr Leu Arg Glu His Pro
Glu Arg Ala Gln Glu Val Phe Ser 35 40
45 Glu Ser Leu Lys 50
10936PRTStaphylococcus sp. 109Val Lys Asn Asn Leu Arg Tyr Gly Ile Arg Lys
His Lys Leu Gly Ala1 5 10
15 Ala Ser Val Phe Leu Gly Thr Met Ile Val Val Gly Met Gly Gln Asp
20 25 30 Lys Glu Ala
Ala 35 1106PRTStaphylococcus sp. 110Asp Arg His Phe Leu Asn1
5 1114PRTStaphylococcus sp. 111Gly Asn Tyr Asp1
1125PRTStaphylococcus sp. 112Arg Arg Tyr Pro Phe1 5
1136PRTStaphylococcus sp. 113Lys Thr Thr Leu Leu Lys1 5
1147PRTStaphylococcus sp. 114Gly Val Thr Thr Ser Leu Ser1
5 1155PRTStaphylococcus sp. 115Val Asp Trp Leu Arg1
5 1164PRTStaphylococcus sp. 116Arg Gly Phe Leu1
11715PRTStaphylococcus sp. 117Lys Ile Lys Val Tyr Val Gly Asn Tyr Asp Phe
Trp Tyr Gln Ser1 5 10 15
11816PRTStaphylococcus sp. 118Thr Val Ile Val Val Ser His Asp Arg His
Phe Leu Tyr Asn Asn Val1 5 10
15 11915PRTStaphylococcus sp. 119Thr Glu Thr Phe Leu Arg Gly
Phe Leu Gly Arg Met Leu Phe Ser1 5 10
15 12035DNAArtificial SequecneStaphylococcal primer
120cgcggatccg cagattctga tattaatatt aaaac
3512133DNAArtificial SequenceStaphylococcal primer 121cccaagcttt
taatttgtca tttcttcttt ttc
3312234DNAArtificial SequenceStaphylococcal primer 122cgcggatccg
ctgggtctaa taattttaaa gatg
3412330DNAArtificial SequenceStaphylococcal primer 123cccaagcttt
tatggaataa cgatttgttg
3012432DNAArtificial SequenceStaphylococcal primer 124cgcggatcca
gtgaaaatag tgttacgcaa tc
3212533DNAArtificial SequenceStaphylococcal primer 125cccaagcttt
tactctggaa ttggttcaat ttc
3312631DNAArtificial SequenceStaphylococcal primer 126cgcggatcca
cacaaacaac tgcaactaac g
3112735DNAArtificial SequenceStaphylococcal primer 127cccaagcttt
tatgctttgt gattcttttt caaac
3512826DNAArtificial SequenceStaphylococcal primer 128cgcggatcca
acacgcaaca aacttc
2612936DNAArtificial SequenceStaphylococcal primer 129ggaactgcag
ttatttccag aatgataata aattac
3613028DNAArtificial SequenceStaphylococcal primer 130cgcggatccg
cagaacatac gaatggag
2813132DNAArtificial SequenceStaphylococcal primer 131cccaagcttt
tatgtttctt cttcgtagta gc
3213228DNAArtificial SequenceStaphylococcal primer 132cgcggatccg
aggagaattc agtacaag
2813331DNAArtificial SequenceStaphylococcal primer 133cccaagcttt
tattcgtcat catagtatcc g
3113425DNAArtificial SequenceStaphylococcal primer 134aaaagtactc
accaccacca ccacc
2513529DNAArtificial SequenceStaphylococcal primer 135aaaagtactc
acttgattca tcgcttcag
2913633DNAArtificial SequenceStaphylococcal primer 136gcgcgccatg
gcacaagctt ctacacaaca tac
3313732DNAArtificial SequenceStaphylococcal primer 137gcgcgctcga
gatggatgaa tgcatagcta ga
3213848DNAArtificial SequenceStaphylococcal primer 138gcatccatgg
caccatcacc atcaccacga agtaaacgtt gatcaagc
4813934DNAArtificial SequenceStaphylococcal primer 139agcactcgag
ttagaatccc caagcaccta aacc
3414029DNAArtificial SequenceStaphylococcal primer 140gcacccatgg
cagaaaatac aaatacttc
2914131DNAArtificial SequenceStaphylococcal primer 141ttttctcgag
cattttagat tgactaagtt g
3114233DNAArtificial SequenceStaphylococcal primer 142caagtcccat
ggctgagacg acacaagatc aac
3314331DNAArtificial SequenceStaphylococcal primer 143cagtctcgag
ttttacagct gtttttggtt g
3114430DNAArtificial SequenceStaphylococcal primer 144agctcatatg
gcttatactg ttactaaacc
3014529DNAArtificial SequenceStaphylococcal primer 145gcgcctcgag
tttatattgt gggatgtcg
2914634DNAArtificial SequenceStaphylococcal primer 146caagtcccat
ggcaacagaa gctacgaacg caac
3414735DNAArtificial SequenceStaphylococcal primer 147accagtctcg
agtaattctt tagctttaga gcttg
3514833DNAArtificial SequenceStaphylococcal primer 148tattctcgag
gctttgagtg tgtccatcat ttg
3314932DNAArtificial SequenceStaphylococcal primer 149gaagccatgg
cagcagctga agaaacaggt gg
3215030DNAArtificial SequenceStaphylococcal primer 150gattacacca
tggttaaacc tcaagcgaaa
3015130DNAArtificial SequenceStaphylococcal primer 151aggtgtctcg
agtgcgattg tagcttcatt
3015296PRTStaphylococcus sp.MISC_FEATURE(2)..(2)Xaa is any amino acid
152Leu Xaa Gly Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Xaa Xaa 1
5 10 15 Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln Xaa Xaa Xaa Xaa 20
25 30 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Xaa Xaa Xaa Xaa 35 40
45 Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Met Xaa Xaa Leu
Xaa Xaa 50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 65
70 75 80 Xaa Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala 85
90 95 153127PRTStaphylococcus
sp.MISC_FEATURE(1)..(19)Xaa is any amino acid 153Xaa Xaa Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 1 5
10 15 Xaa Xaa Xaa Leu Xaa Gly Xaa Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Xaa Xaa 20 25
30 Ala Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln
Xaa 35 40 45 Xaa
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 50
55 60 Xaa Xaa Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Leu Xaa Xaa Xaa Met Xaa Xaa 65 70
75 80 Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
Xaa Xaa Xaa Xaa Xaa 85 90
95 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110 Xaa Xaa
Ala Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 115
120 125 154127PRTStaphylococcus
sp.misc_feature(1)..(5)Xaa is any amino acid 154Xaa Xaa Xaa Xaa Xaa Xaa
Xaa Xaa Ala Xaa Xaa Xaa Xaa Xaa Xaa Ala 1 5
10 15 Lys Xaa Ala Leu Xaa Gly Xaa Xaa Asn Leu Xaa
Xaa Ala Lys Xaa Xaa 20 25
30 Ala Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Leu Asn Xaa Ala Gln
Lys 35 40 45 Xaa
Xaa Leu Xaa Xaa Gln Xaa Xaa Xaa Ala Xaa Xaa Val Xaa Xaa Val 50
55 60 Xaa Xaa Xaa Xaa Xaa Xaa
Ala Xaa Xaa Leu Xaa Xaa Ala Met Xaa Xaa 65 70
75 80 Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr
Lys Xaa Ser Xaa Asn 85 90
95 Xaa Xaa Xaa Ala Asp Xaa Xaa Lys Xaa Xaa Ala Xaa Xaa Xaa Ala Val
100 105 110 Xaa Xaa
Ala Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 115
120 125
User Contributions:
Comment about this patent or add new information about this topic:
People who visited this patent also read: | |
Patent application number | Title |
---|---|
20220290405 | FILLING EARTH INTO A VEHICLE USING A COOPERATIVE FLEET OF VEHICLES |
20220290404 | Sensor Retrofit to Autonomously Actuate An Excavation Vehicle |
20220290403 | Construction Machine |
20220290402 | WORK MACHINE |
20220290401 | DISPLAY SYSTEM, REMOTE OPERATION SYSTEM, AND DISPLAY METHOD |