Bacteriophage and their uses

Abstract

riophage capable of lysing a P. acnes bacterium and incapable of lysing a bacterium which is not P. acnes, and which is incapable of sustaining lysogeny in a bacterium. There is also provided a pharmaceutical composition comprising such a bacteriophage.

Description

[0001]The invention relates to bacteriophage and their uses. In particular, though not exclusively, it relates to their use in compositions for the treatment of acne.

BACKGROUND

[0002]Acne vulgaris is one of the most common diseases of the skin and in cases of extreme disfigurement can sometimes have severe consequences for the personality development of young people with ensuing social and economic problems. Adolescents suffering from acne show higher levels of anxiety, greater social inhibition and increased aggression compared to non-acne individuals. Amongst skin diseases, acne is the second highest cause of suicides.

[0003]Acne is an exclusively human disease and a unique condition of human sebaceous follicles of the face, chest and back. Spontaneous regression is common, taking about 15 years to complete. However, in about 5 percent of cases, acne persists beyond the age of 25 years and extends into the fourth and fifth decades of life. The earlier the symptoms start, the more severe is the course of the disease. The prevalence of the disease does not reflect any preference for male or female but usually the course is more severe in males.

[0004]The onset of the disease in an individual coincides with entry into puberty and is associated with an androgen-driven rise in sebum excretion rate and an increased colonisation of the sebaceous follicles with Propionibacterium acnes (P. acnes). Recent data indicates that the initiation of individual lesions is primarily inflammatory rather than via keratinocyte hyperproliferation.

[0005]Contrary to popular opinion, hygiene and diet have little or no effect on the aetiology of acne. Acne can be exacerbated by external factors such as friction (acne mechanica) (Shalita A R (1983) Cosmetics and Toiletries 98: 57-60) and pore-clogging cosmetics (acne cosmetica) (Mills O. H. & Kilgman A. M. (1988) Dermatol. Clin. 1: 365-370). The bacterium P. acnes is an inhabitant of the human skin and forms a major part of the natural skin flora. There is a wealth of circumstantial evidence implicating P. acnes as a major factor in the disease: increased colonisation of the skin by P. acnes is associated with the onset of the disease; patients with severe acne are significantly more sensitised to P. acnes than normal individuals; the overall immunological status of patients is elevated compared to acne-free individuals of the same age; successful antibiotic treatment reduces the density of P. acnes on the skin; and antibiotic therapeutic failure is associated with the presence of antibiotic resistant P. acnes on the skin of the patient.

[0006]Current treatments for acne focus on various factors contributing to the disease. In summary, anti-comedonal treatments include retinoids and azelaic acid (topical treatments) and isotretinoin (oral treatments); anti-P. acnes treatments include benzoyl peroxide, azelaic acid, erythromycin, tetracycline and clindamycin (topical treatments) and tetracycline, erythromycin, minocycline and trimethoprim (oral treatments); anti-inflammatory treatments include tetracycline, erythromycin, clindamycin and nicotinamide (topical treatments) and tetracycline, minocycline, trimethoprim and isotretinoin (oral treatments); and anti-seborrhoeic treatments include spironolactone (topical treatments) and Dianette® and isotretinoin (oral treatments).

[0007]The more common mild and moderate cases of acne are treated with antibiotics, usually topically. There are increasing concerns emerging over the use of antibiotics for acne, where treatments last for long periods of time, up to 2-3 years in some cases. The concerns are two fold. First, the emergence of antibiotic resistant P. acnes world-wide with the consequence of reducing their efficacy for acne therapy. Second and possibly more importantly, there is the selection of an increasing pool of antibiotic resistant genes in the commensal microflora, mainly coagulase-negative staphylococci and corynebacteria, on patients' skin. These resistance genes may be horizontally transferred to related species, e.g. Staphylococcus aureus, which is a major opportunistic pathogen in the hospital and community environments. Therefore all efforts are required to restrict the use of antibiotics over extended treatment periods as used in the treatment of acne. Obtaining licences to market antibiotic therapies for acne is becoming especially difficult.

[0008]Side effects from these treatments are commonplace. Mild irritant dermatitis is associated with virtually all topical therapies (Cunliffe W. J., (2001) Pharmaceut. J. 267 749-752). Oral courses of antibiotics have side effects regardless of the condition for which they are prescribed and these often result from their lack of specificity, unbalancing (in due course) much of the bacterial flora in many sites in the body. This leaves room for resistant flora to flourish, resulting in, for example, vaginal candidiasis in women. Retinoid treatment has many side effects: it is a teratogen; causes cheilitis, facial dermatitis and conjunctivitis; leads to secondary skin infections; and has been associated with mood swings and depression.

[0009]Therefore, there is a need to develop new approaches for acne therapy which specifically target P. acnes.

[0010]The idea of employing bacteriophage (naturally occurring bacterial viruses) for the treatment or prevention of bacterial diseases was realised relatively soon after the discovery of phage (the words "bacteriophage" and "phage" are used interchangeably throughout this specification) by Felix d'Herelle in 1917. The fact that bacteriophage can specifically infect a bacterial host and rapidly kill it suggested to d'Herelle that this was potentially a very effective way of controlling bacterial infection in man (for review, see "Felix d'Herelle and the Origins of Molecular Biology" William C. Summers (Yale University Press, ISBN 0-300-07127-2)). This potential was never fully realised because of the advent of the antibiotic era, but phage therapy has been pursued since then, in many cases successfully, in former states of the USSR and Eastern Europe.

[0011]The emergence of drug resistance and the difficulty in developing novel antibiotics and vaccines has highlighted a growing need to find alternative methods of treatment.

[0012]WO03/080823 discloses a method for generating candidate bacteriophage for use in therapy by mutating temperate bacteriophage and producing a cocktail of phages. This disclosure specifically selects lysogenic phage, observing that for some bacteria they are more numerous and, therefore, easier to isolate than lytic phage. The phage then have to be mutated to produce lytic vir mutants, in order to avoid the problems associated with lysogenic phage as a therapy, as discussed further below. Treatment of P. acnes is mentioned.

[0013]EP0414304 relates to the use of bacteriophage to kill bacteria, including P. acnes. There is no disclosure of a bacteriophage capable of lysing multiple strains of P. acnes bacteria and yet which is incapable of lysing a bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium.

[0014]Jong et al (Med. Microbiol. Immunol. 161 (1975) 263-271) describes isolation of P. acnes phage. The paper focuses on the classification of the phage and does not disclose a bacteriophage capable of lysing multiple strains of P. acnes bacteria and yet which is incapable of lysing a bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium.

[0015]Puhvel & Reisner (Amer. Soc. Microbiol. 72 (1972) V201) is an abstract relating to the generation of lysogenic phage-resistant strains of P. acnes.

[0016]WO01/51066 relates to the use of bacteriophage to reduce risk of infection or sepsis, particularly in immunocompromised patients. The disclosed methodology aims to achieve the numerical reduction or elimination of various members of the body's natural bacterial flora, in order to reduce the chance of them causing disease in immunocompromised patients. This is specifically risk reduction rather than cure and is concerned in particular with infections which complicate conditions such as certain cancers, AIDS and cystic fibrosis and which complicate the condition of transplant patients. No mention is made of treatment of P. acnes.

[0017]U.S. Pat. No. 6,121,036 relates to a purified, host specific, non-toxic, wide host range bacteriophage preparation containing at least two phage. The document describes some of the features of an effective phage therapy--that it should be safe, have broad host range and kill a large proportion of bacteria strains--and indicates that such a preparation of appropriate phage could be used to treat P. acnes infections. However, no disclosure is made about which phage are suitable for this purpose or that such safe, lytic, broad host range phage exist for P. acnes.

[0018]WO02/07742 purports to disclose a method for potentiating a wider host range for a phage by cloning tail protein-encoding genes from another phage with different host specificity. The document indicates that wide specificity is desirable from a phage therapy point of view but, rather than selecting from naturally occurring phage variants, describes the synthetic construction of a hybrid bacteriophage with dual tail fibre types, therefore having corresponding dual host specificity. This specificity is hypothetically extended to apply the invention in the engineering of a phage which can infect not only different species strains but different bacteria within a species and even within different genera. However, there is no evidence for this potential beyond results showing that a hybrid phage had been created having the ability to infect two different strains of Escherichia coli. The application of a suitably modified phage for gene therapy in humans is also contemplated. Specific phage, modified or unmodified, for the treatment of acne are not disclosed. There is no mention of a P. acnes bacteriophage with a single host species specificity but with multiple strain specificity.

[0019]US2005/0032036 describes a method for sorting through a phage collection and determining the composition of a phage cocktail in order to optimise broad host range infection and lysis, particularly in reference to Pseudomonas and Staphylococcus strains. No disclosures are made in relation to the field of acne phage therapy.

[0020]WO2005/009451 relates in particular to the use of bacteriophage as a part of a combination therapy with traditional, chemical antibiotics, particularly in the treatment of Pseudomonas aeruginosa infections and particularly in the treatment of bacteria within biofilms. It describes the difficulty in finding phage with sufficiently broad host specificity to be of therapeutic value for treatment of any given infection and advocates the use of multiple bacteriophage types for therapy, whether simultaneously, separately or sequentially. It also indicates that greater virulence in a phage can be induced artificially by genetic manipulation methods to produce phage with broader specificity or greater infection potential. There is no mention of P. acnes, which is not characterised by biofilm formation.

[0021]US2004/0241825 discloses several methods for genetically labelling bacteriophage (with a non-functional stretch of DNA that can be detected by, for example, PCR, enabling identification of the phage), identifying non-cross reacting bacteriophage (a multi-step process to isolate phage against the target host and, from these, isolating bacteriophage which do not infect more than 5% of non-pathogenic, non-target hosts) and, finally, a method for selecting phage that are resistant to genetic modification by host bacteria (which involves infecting bacteria with a sample of bacteriophage, isolating progeny phage and comparing the restriction digest patterns of the original bacteriophage and the progeny to identify any differences that would be indicative of genetic modification). Implicit in this disclosure is the difficulty in identifying suitable candidate bacteriophage for use in a therapy. The application of this methodology to P. acnes is not described:

[0022]Several conference presentations by the research group of Michael Davis at Central Connecticut State University have outlined plans to identify lytic phage having broad host range specificity (Vieira T. and Davis M. A. (1999) Viruses as Therapeutic Agents for Treating Bacterial Infections. Poster presentation on Apr. 24, 1999 at the 53rd Annual Eastern Colleges Science Conference, Sacred Heart University, Fairfield Conn.; Jedrzkiewicz B. and Davis M. A. (2000) Combating the Antibiotic Resistance Crisis: Therapeutic Use of Bacteriophages (Viruses) for Treating Acne, A Bacterial Disease. Poster presentation on Apr. 1, 2000 at the 54th Annual Eastern Colleges Science Conference, Wagner College, Staten Island N.Y.; Hany C. et al., (2001) The Use of Bacteriophage to Treat Acne, A Bacterial Disease. Poster presentation on Mar. 31, 2001 at the 55th Annual Eastern Colleges Science Conference, Wilkes University, Wilkes-Barre Pa.; Armack S. et al. (2002) Bacteriophage Therapy For The Treatment Of The Bacterial Disease Acne. Poster presentation on Apr. 27, 2002 at the 56th Annual Eastern Colleges Science Conference, Niagara University, Niagara N.Y.; Arminti K. et al. (2003) Bacteriophage Therapy For The Disease Acne: Identification And Purification Of Candidate Bacteriophage. Poster presentation on Apr. 12, 2003 at the 57th Annual Eastern Colleges Science Conference, Ithaca College, Ithaca N.Y.; Geronimo J. et al (2004) Bacteriophage Therapy For the Skin Disease Acne. Poster presentation on Apr. 2, 2004 at the 58th Annual Eastern Colleges Science Conference, Manhattan College, Riverdale N.Y.). No disclosures have been made in relation to the specific properties of such phage or to specific phage isolates.

DESCRIPTION OF THE INVENTION

[0023]According to a first aspect of the invention there is provided a bacteriophage capable of lysing a P. acnes bacterium and incapable of lysing any bacterium which is not P. acnes, and which is incapable of sustaining lysogeny in a bacterium.

[0024]Such a phage has the ability to infect a wide range of bacterial strains within a species but with absolute species specificity. This is one of the most important and usually unachievable aims in the development of an effective phage therapy. In addition, a bacteriophage according to the invention is purely lytic, i.e. incapable of entering the lysogenic phase of the bacteriophage life cycle, a quiescent stage which is undesirable in the creation of an effective therapy and is also unacceptable from a regulatory point of view.

[0025]Advantageously, such a bacteriophage can be used in the treatment of acne. No side effects have been reported or are expected in the use of phage therapy, whether delivered systemically, orally or topically. The bacteriophage is specific to P. acnes and therefore leaves other members of the skin flora unaffected, reducing the opportunity for the overgrowth of potentially harmful flora. The protective nature of the normal resident microflora is therefore maintained. The specificity of a phage therapy approach to treatment of acne also eliminates the possibility of drug resistance emerging in other members of the microflora: other antibacterial treatments offer a broad brush stroke approach to eliminating bacteria and therefore, under the appropriate conditions, provide an opportunity for developing drug resistance not only in P. acnes but in other important commensals with pathogenic potential, e.g. Staphylococcus aureus. A further advantage of bacteriophage treatment is that it is self regulating: as the population of host P. acnes cells reduces, so will the bacteriophage numbers. In addition, such a bacteriophage can be used as a general prophylactic measure; the use of antibiotics in unprescribed cosmetic products (such as face washes, etc) is undesirable for many reasons relating to safety and the issue of antibiotic resistance. In fact there are strong arguments for limiting the use of antibiotics to reduce the incidence of resistance. Specificity of the bacteriophage means that it is suitable for widespread use in these situations and could be employed as part of a general hygiene routine for the prevention of acne. In addition, the use of the bacteriophage may be effective even against bacterial strains which have become resistant to antibiotics.

[0026]As mentioned above, the use of a bacteriophage which can lyse P. acnes but is incapable of sustaining lysogeny has the advantage that the bacteriophage cannot lie dormant within a bacterium, but must lyse the bacterium and hence kill it.

[0027]Preferably, the bacteriophage lacks the ability to express at least one gene necessary for sustaining lysogeny. The term "lacks the ability to express" is intended to indicate that the bacteriophage lacks the ability to produce a fully functional protein product necessary to sustain lysogeny, for example, as the result of one or more point mutations or full or partial deletions of the genome. More preferably, the phage has a genome which lacks all or part of at least one gene necessary for sustaining lysogeny. Alternatively or additionally, the phage may comprise defects (e.g. mutations, insertions or deletions) in the genome in non-coding regions which may, nonetheless, affect the ability of the phage to sustain lysogeny, for example defects in the genome integration site(s) (e.g. the /att/ site) or in the repressor binding site. The phage is preferably naturally occurring and isolated, with the added advantage that artificial mutations need not be introduced into the bacteriophage. Such mutations, whilst not ruled out, could have potentially unknown results which could be harmful to the individual to whom the bacteriophage is administered. If the phage contains artificial mutations, or is otherwise non-naturally occurring, it is still preferred that the phage is obtained in an isolated state.

[0028]In a preferred embodiment, the bacteriophage according to this aspect of the invention is capable of lysing a plurality of strains of the P. acnes bacterium. For example, the bacteriophage according to this aspect of the invention may be capable of lysing 5 strains of the P. acnes bacterium, preferably at least 10 strains, more preferably at least 16 strains, or at least 17 strains, or at least 18 strains, or at least 19 strains, or at least 20 strains. Most preferably, the bacteriophage is capable of lysing at least 21 strains.

[0029]Preferably, the bacteriophage according to this aspect of the invention is isolated and selected from those phage characterised hereinafter as: 103609; 103672; and 1894.

[0030]The following isolates of bacteriophage have been deposited under the terms of the Budapest Treaty at The National Collection of Industrial, Marine and Food Bacteria (NCIMB), Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen, AB21 9YA, United Kingdom, under the following accession numbers: Accession no. NCIMB 41332 (isolate PA6); Accession no. NCIMB 41334 (isolate 1874); Accession no. NCIMB 41333 (isolate 1878); Accession no. NCIMB 41335 (isolate 1905); Accession no. NCIMB 41349 (isolate 1894); Accession no. NCIMB 41350 (isolate 103609); Accession no. NCIMB 41351 (isolate 103672). The host bacteria, P. acnes, AT1 was also deposited as NCIMB 41336.

[0031]The bacteriophage may have a genome which comprises the DNA sequence of SEQ ID NO:3, or a genome having sequence identity of at least 87% with the DNA sequence of SEQ ID NO:3, more preferably sequence identity of at least 88% with that sequence, yet more preferably sequence identity of at least 90% with that sequence, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99% with that sequence. Alternatively or in addition, the bacteriophage may have a genome comprising a functional fragment of the DNA sequence of SEQ ID NO:3. For example, the functional fragment may be selected from within the Open Reading Frames shown in FIG. 2. Alternatively, the functional fragment may comprise a DNA sequence having sequence identity of at least 95% with the DNA sequence of FIG. 6, preferably sequence identity of at least 96%, more preferably sequence identity of at least 97% with that sequence, most preferably sequence identity of at least 98% or 99% with that sequence. In a preferred embodiment, the functional fragment comprises the DNA sequence of FIG. 6.

[0032]Alternatively, the bacteriophage may have a genome which comprises the DNA sequence of SEQ ID NO:4, or a genome having sequence identity of at least 88% with the DNA sequence of SEQ ID NO:4, more preferably sequence identity of at least 89% with that sequence, yet more preferably sequence identity of at least 90% with that sequence, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99% with that sequence. Alternatively or in addition, the bacteriophage may have a genome comprising a functional fragment of the DNA sequence of SEQ ID NO:4. For example, the functional fragment may be selected from within the Open Reading Frames shown in FIG. 3. Alternatively, the functional fragment may comprise a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:7, preferably sequence identity of at least 96%, more preferably sequence identity of at least 97% with that sequence, most preferably sequence identity of at least 98% or 99% with that sequence. In a preferred embodiment, the functional fragment comprises the DNA sequence of SEQ ID NO:7.

[0033]In a further alternative, the bacteriophage may have a genome which comprises the DNA sequence of SEQ ID NO:5, or a genome having sequence identity of at least 88% with the DNA sequence of SEQ ID NO:5, more preferably sequence identity of at least 89% with that sequence, yet more preferably sequence identity of at least 90% with that sequence, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99% with that sequence. Alternatively or in addition, the bacteriophage may have a genome comprising a functional fragment of the DNA sequence of SEQ ID NO:5. For example, the functional fragment may be selected from within the Open Reading Frames shown in FIG. 4. Alternatively, the functional fragment may comprise a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:8, preferably sequence identity of at least 96%, more preferably sequence identity of at least 97% with that sequence, most preferably sequence identity of at least 98% or 99% with that sequence. In a preferred embodiment, the functional fragment comprises the DNA sequence of SEQ ID NO:8.

[0034]Alternatively or additionally, the functional fragment may comprise the DNA sequence of one or more of:

a DNA sequence having sequence identity of at least 63%, 70%, 80%, 90%, 95% or 99% with ORF1 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF2 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF3 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF4 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 89%, 90%, 95% or 99% with ORF5 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 92%, 95% or 99% with ORF6 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 96%, 97%, 98% or 99% with ORF7 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 94%, 95% or 99% with ORF8 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 95%, 97%, 98% or 99% with ORF9 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91-%, 95% or 99% with ORF10 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 93%, 95% or 99% with ORF11 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 97%, 98% or 99% with ORF12 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 99% with ORF13 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF14 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 93%, 95% or 99% with ORF15 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 94%, 95% or 99% with ORF16 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 97%, 98% or 99% with ORF17 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 67%, 70%, 80%, 90%, 95% or 99% with ORF18 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 80%, 90%, 95% or 99% with ORF19 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 88%, 90%, 95% or 99% with ORF20 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 86%, 90%, 95% or 99% with ORF21 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 97%, 98% or 99% with ORF22 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 98% or 99% with ORF23 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 93%, 95% or 99% with ORF24 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 87%, 90%, 95% or 99% with ORF25 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 63%, 70%, 80%, 90%, 95% or 99% with ORF26 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 80%, 90%, 95% or 99% with ORF27 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 78%, 80%, 90%, 95% or 99% with ORF28 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 66%, 70%, 80%, 90%, 95% or 99% with ORF29 of SEQ ID NO:3, 4 or 5; and/ora DNA sequence having sequence identity of at least 87%, 90%, 95% or 99% with ORF30 of SEQ ID NO:3, 4 or 5.

[0035]Preferably, the functional fragment comprises a DNA sequence which is conserved between all of SEQ ID NO:3, 4 and 5.

[0036]The bacteriophage may have a genome having sequence identity of at least 88% with the genome of the bacteriophage deposited under Accession No. NCIMB 41349, preferably sequence identity of at least 89%, more preferably sequence identity of at least 90%, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99%.

[0037]The bacteriophage may have a genome having sequence identity of at least 87% with the genome of the bacteriophage deposited under Accession No. NCIMB 41350, preferably sequence identity of at least 88%, more preferably sequence identity of at least 90%, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99%.

[0038]The bacteriophage may have a genome having sequence identity of at least 88% with the genome of the bacteriophage deposited under Accession No. NCIMB 41351, preferably sequence identity of at least 89%, more preferably sequence identity of at least 90%, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99%. The term "sequence identity", as used throughout this specification, is calculated as the percentage of nucleotides present in the smaller of the two sequences to be compared that may also be found in the larger of the two sequences, the nucleotides preferably being arranged in the same order in both sequences. The skilled person would readily be able to determine the level of sequence identity between sequences, for example by use of the Blast analysis tool at http://www.ncbi.nlm.nih.gov/BLAST/, using the default parameter settings. Preferably, the length of the shorter of the two sequences being compared is at least 60% of the length of the longer of the two sequences, more preferably at least 70% of the length, yet more preferably at least 80% of the length and still more preferably at least 90%, 95%, 96% 97% 98% or 99% of the length. In a most preferred embodiment, the sequences to be compared are identical in length.

[0039]The term "functional fragment", as used throughout this specification, indicates a portion of the full length sequence which has substantially identical functionality to the full length sequence itself. For example, when reference is made to a functional fragment of a bacteriophage genome, this indicates that the fragment, when contained in a bacteriophage, results in a bacteriophage according to the invention, i.e. a bacteriophage capable of lysing a P. acnes bacterium and incapable of lysing any bacterium which is not P. acnes, and which is incapable of sustaining lysogeny in a bacterium. Preferably, the size of the functional fragment is at least 30% of the size of the full length sequence, more preferably at least 40% of the size, yet more preferably at least 50% of the size, yet more preferably at least 60%, 70%, 80%, 85%, 90% or 95% of the size.

[0040]In a preferred embodiment, the bacteriophage has a genome which does not comprise one or more of the nucleotide sequences shown in SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13. Without wishing to be bound by theory, it is considered that the properties of a bacteriophage according to the invention, namely that the bacteriophage is capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium, may be associated with the absence of one or more of these sequences from the genome of the bacteriophage.

[0041]Preferably, the bacteriophage is isolated and is selected from those herein characterised as 103609, 103672 and 1894.

[0042]The bacteriophage according to the first aspect of the invention may be modified to comprise a marker molecule. The term "marker molecule", as used throughout this specification, is intended to include, but not be limited to, markers or tags such as biotin, a his-tag or a label recognisable by a binding partner such as an antibody, useable, for example, to isolate the bacteriophage. Markers suitable for use in affinity purification processes include glutathione-S-transferase (GST), protein A, ScFv and lectins. Other modifications of the bacteriophage may be made, e.g. for reducing phage antigenicity, including use of a PEG (polyethylene glycol) conjugate or a polysialic acid conjugate. Modifications may also include the addition of molecules which enhance the lethality of the phage to the bacterial host. Examples are given in Westwater C. et al. (2003) Antimicrob. Agents Chemotherapeutics 47: 1301-1307. Other suitable markers and modifications will be well known to the skilled person. The marker molecule may be incorporated at the DNA level or may be attached chemically at the phage surface.

[0043]According to a second aspect of the invention, there is provided an isolated polynucleotide having the nucleotide sequence of the genome of a bacteriophage according to the first aspect of the invention. Alternatively or additionally, the polynucleotide may comprise the nucleotide sequence of any one of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 or the complement thereof, or may comprise a functional fragment of the DNA sequence of any one of SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5; when a bacteriophage comprises a polynucleotide according to the second aspect of the invention, it has the properties of a bacteriophage according to the first aspect of the invention.

[0044]Preferably, the polynucleotide has sequence identity of at least 87% with the DNA sequence of SEQ ID NO:3, preferably sequence identity of at least 88%, more preferably sequence identity of at least 90%, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99% with that sequence.

[0045]In an alternative preferred embodiment, the polynucleotide has sequence identity of at least 88% with the DNA sequence of SEQ ID NO:4, preferably sequence identity of at least 89%, more preferably sequence identity of at least 90%, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99% with that sequence.

[0046]In a further alternative preferred embodiment, the polynucleotide has sequence identity of at least 88% with the DNA sequence of SEQ ID NO:5, preferably sequence identity of at least 89%, more preferably sequence identity of at least 90%, most preferably sequence identity of at least 95%, 96%, 97%, 98% or 99% with that sequence.

[0047]The functional fragment may be selected from one or more of the Open Reading Frames (ORFs) shown in any of FIG. 2, 3 or 4, i.e. the ORFs within SEQ ID NO:3, 4, or 5 (respectively), the boundaries of which are defined in Table 5 below. Alternatively, the functional fragment may comprise a DNA sequence having sequence identity of at least 95% with any one of the DNA sequences selected from SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8, preferably sequence identity of at least 96%, more preferably sequence identity of at least 97% with any one of those sequences, most preferably sequence identity of at least 98% or 99% with any one of those sequences. In a more preferred embodiment, the functional fragment comprises the DNA sequence of SEQ ID NO:6, SEQ ID NO:7 or SEQ ID NO:8.

[0048]Alternatively or additionally, the functional fragment may comprise one or more of:

a DNA sequence having sequence identity of at least 63%, 70%, 80%, 90%, 95% or 99% with ORF1 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF2 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF3 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF4 of SEQ ID NO:3, 4 or 45;a DNA sequence having sequence identity of at least 89%, 90%, 95% or 99% with ORF5 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 92%, 95% or 99% with ORF6 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 96%, 97%, 98% or 99% with ORF7 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 94%, 95% or 99% with ORF8 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 95%, 97%, 98% or 99% with ORF9 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF10 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 93%, 95% or 99% with ORF11 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 97%, 98% or 99% with ORF12 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 99% with ORF13 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 91%, 95% or 99% with ORF14 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 93%, 95% or 99% with ORF15 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 94%, 95% or 99% with ORF16 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 97%, 98% or 99% with ORF17 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 67%, 70%, 80%, 90%, 95% or 99% with ORF18 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 80%, 90%, 95% or 99% with ORF19 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 88%, 90%, 95% or 99% with ORF20 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 86%, 90%, 95% or 99% with ORF21 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 97%, 98% or 99% with ORF22 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 98% or 99% with ORF23 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 93%, 95% or 99% with ORF24 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 87%, 90%, 95% or 99% with ORF25 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 63%, 70%, 80%, 90%, 95% or 99% with ORF26 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 80%, 90%, 95% or 99% with ORF27 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 78%, 80%, 90%, 95% or 99% with ORF28 of SEQ ID NO:3, 4 or 5;a DNA sequence having sequence identity of at least 66%, 70%, 80%, 90%, 95% or 99% with ORF29 of SEQ ID NO:3, 4 or 5; and/ora DNA sequence having sequence identity of at least 87%, 90%, 95% or 99% with ORF30 of SEQ ID NO:3, 4 or 5.

[0049]The polynucleotide may comprise one or more of the Open Reading Frames shown in any of FIG. 2, 3 or 4.

[0050]Preferably, the polynucleotide has a nucleic acid sequence which does not comprise one or more of the sequences shown in SEQ ID NO:9. SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13. Without wishing to be bound by theory, it is considered that the properties of a bacteriophage containing a polynucleotide according to the second aspect of the invention, namely that the bacteriophage is capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium, may be associated with the absence of one or more of these sequences from the polynucleotide according to the second aspect of the invention.

[0051]The polynucleotide may further comprise a nucleotide sequence encoding a marker molecule.

[0052]According to a third aspect of the invention there is provided an isolated polypeptide having an amino acid sequence encoded by the polynucleotide according to the second aspect of the invention.

[0053]According to a fourth aspect of the invention, there is provided a composition comprising at least one bacteriophage according to the first aspect of the invention and an adjuvant, carrier or vehicle.

[0054]Preferably, the composition is for use in the prevention or treatment of acne, or for use to improve the appearance of a mammal (preferably a human), the bacteriophage being present in an effective amount.

[0055]The term "treatment" (and equivalent terms such as "treating", "treat" etc), as used throughout this specification, is intended to indicate the reduction or elimination of the occurrence of the symptoms of acne. For example, symptoms include visible marks on the face such as papules (small raised red spots less than 5 mm in diameter), superficial pustules and deeper lesions (nodules and pustules larger than 5 mm in diameter). The deeper lesions can lead to scarring.

[0056]The composition preferably comprises two or more different isolates of bacteriophage. Each of the two or more isolates of bacteriophage may be a bacteriophage according to the first aspect of the invention.

[0057]Additionally or alternatively, the composition may comprise an isolated polynucleotide according to the second aspect of the invention or an isolated polypeptide according to the third aspect of the invention. Where the composition is for use in the prevention or treatment of acne, or for use to improve the appearance of a mammal (preferably a human), the isolated polynucleotide and/or isolated polypeptide is present in an effective amount.

[0058]The composition may be in a form suitable for oral, intravenous or topical administration. For example, the composition may be in a form suitable for oral administration and be a liquid, powder or tablet. Alternatively, the composition may be in a form suitable for intravenous administration and be a liquid, or a solid dissolvable in a liquid. In a further alternative, the composition may be in a form suitable for topical administration and be in the form of a cream, solution, powder, spray, aerosol, capsule, solid or gel, or may be bonded to a solid surface. The composition may also form part of a face wash, soap, application stick, cosmetic or dressing.

[0059]The bacteriophage, polynucleotide or polypeptide according to the invention contained in the composition may be within, or a part of, liposomes, capsules, carrier particles or, indeed, any other method of maintaining the bacteriophage, polynucleotide or polypeptide in a separate microenvironment within the composition. Alternatively, the bacteriophage, polynucleotide or polypeptide may be added directly to the composition, for example a bacteriophage may be added in a freeze-dried form.

[0060]The composition according to this aspect of the invention may further comprise at least one further agent selected from antibiotics, anti-comedonals, anti-P. acnes agents, anti-inflammatories and anti-seborrhoeics.

[0061]The composition may be a pharmaceutical composition or a cosmetic composition.

[0062]According to a fifth aspect of the invention, there is provided a method of preventing or treating acne comprising administering an effective amount of at least one bacteriophage according to the first aspect of the invention and/or of an isolated polynucleotide according to the second aspect of the invention and/or of an isolated polypeptide according to the third aspect of the invention and/or of a composition according to the fourth aspect of the invention to an individual in need of such prevention or treatment.

[0063]According to a sixth aspect of the invention, there is provided a method of improving the appearance of an individual, the method comprising administering to the individual an effective amount of a bacteriophage according to the first aspect of the invention and/or of an isolated polynucleotide according to the second aspect of the invention and/or of an isolated polypeptide according to the third aspect of the invention and/or of a composition according to the fourth aspect of the invention. Preferably, the individual is a human individual. The method is a non-therapeutic cosmetic method.

[0064]According to a seventh aspect of the invention, there is provided a method for isolating a bacteriophage capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium, comprising: [0065]a) obtaining a sample of bacteria from a skin surface: [0066]b) isolating from the sample bacteriophage which lyse propionibacteria; [0067]c) isolating the bacteriophage to determine if it is capable of lysing at least one P. acnes strain; [0068]d) testing the bacteriophage to determine if it is capable of lysing non-P. acnes bacterial strains; [0069]e) testing the bacteriophage to determine whether it is capable of sustaining lysogeny in a P. acnes strain; [0070]f) detecting a bacteriophage which has been shown in steps (c), (d) and (e) to be capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes, and incapable of sustaining lysogeny in a bacterium.

[0071]According to an eighth aspect of the invention, there is provided a method for identifying a bacteriophage which is capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium, comprising: [0072]a) exposing a P. acnes bacterium to the bacteriophage and determining that the bacterium is lysed; [0073]b) exposing at least one species of bacteria which is not P. acnes bacteria to the bacteriophage and determining that the bacteria are not lysed; [0074]c) determining that the bacteriophage is not capable of sustaining lysogeny in a bacteria.

[0075]Preferably, in step (b), at least three species of bacteria which are not P. acnes are exposed to the bacteriophage, more preferably at least four, at least five, at least 10, at least 20, at least 30, at least 40, or at least 50 different strains of bacteria.

[0076]According to a ninth aspect of the invention, there is provided a bacteriophage isolated or identified using the method according to the seventh or eighth aspects of the invention.

[0077]According to a tenth aspect of the invention, there is provided a bacteriophage obtainable or identifiable by using a method according to the seventh or eighth aspects of the invention.

[0078]Embodiments of the invention will now be described, by way of example only, with reference to the accompanying FIGS. 1-8 in which:

[0079]FIG. 1 shows the arrangement of open reading frames (ORFs) in the PA6 genome, with putative functions of various ORFs indicated;

[0080]FIG. 2 shows the arrangement of open reading frames (ORFs) in the 103609 genome, with putative functions of various ORFs indicated;

[0081]FIG. 3 shows the arrangement of open reading frames (ORFs) in the 103672 genome, with putative functions of various ORFs indicated;

[0082]FIG. 4 shows the arrangement of open reading frames (ORFs) in the 1894 genome, with putative functions of various ORFs indicated;

[0083]FIG. 5 shows a graphical representation of DNA sequence alignment of phages 103672, 103609 and 1894;

[0084]FIG. 6 shows a graphical representation of DNA sequence alignment of PA6 versus 103672, 103609 and 1894;

[0085]FIG. 7 shows an alignment of a portion of the DNA sequences of bacteriophage strains 103609, 103672, 1894 and PA6; and

[0086]FIG. 8 shows an alignment of a further portion of the DNA sequences of bacteriophage strains 103609, 103672, 1894 and PA6

EXPERIMENTAL MATERIALS AND METHODS

1. Materials

[0087]Reinforced Clostridial Agar (RCA; Oxoid CM0151 (Oxoid Ltd., Basingstoke, UK))

[0088]TYG broth (1% (w/v) tryptone (Oxoid L42); 0.5% (w/v) yeast extract (Oxoid L21); 0.25% (w/v) glucose)

[0089]Top agarose (0.7 g low-melting agarose added to 100 ml dH₂O, heated to melt, cooled to 45° C., dispensed into 3 ml volumes and autoclaved.)

[0090]SM buffer (2.92 g NaCl; 1 g MgSO₄.7H₂O; 25 ml 1M Tris-Cl pH7.5; 0.05 g Gelatin; Dissolved in 500 ml dH₂O and autoclaved.)

2. Bacteriophage and Bacteria Collection

2.1 Sampling Method

[0091]The strains of P. acnes and phage isolates used in the screening were obtained from patients attending the Dermatology Department at the Leeds General Infirmary (except P. acnes NCTC737 and DSM16379). The method is based on that described in Williamson P. & Kligman A. M. (1965) J. Invest. Dermatol. 45: 498-503. [0092]a) Place a sterile metal ring onto the surface of the skin and press to ensure a good seal; [0093]b) Pipette 1 ml wash fluid (75 mM phosphate buffer, pH7.9) into the ring; [0094]c) Gently scrub the surface of the skin for 1 min with a sterile. Teflon rod; [0095]d) Remove the wash fluid to a sterile bottle and replace with another 1 ml of sterile wash fluid; [0096]e) Repeat scrubbing procedure then remove the fluid and pool with the first sample; [0097]f) Plate serial dilutions (or spiral plate) of the sample onto RCA containing 6 μg ml^-1 furazolidone (which inhibits growth of staphylococci but not of propionibacteria) and incubate anaerobically for 7 days at 34° C.; [0098]g) Recover individual bacterial colonies or bacteriophage plaques (using method 2.2 described below) and propagate by restreak (bacteria) or the method described below (`Preparation of phage stocks--lysate`) for bacteriophage plaque.

2.2 Preparation of Phage Stocks--Plaque Pick

[0098] [0099]a) Plate out phage-containing bacteria as described above and incubate for 24-48 h; [0100]b) Pick 2-3 plugs of agar from a single plaque into 1 ml SM buffer in a screw-top vial using a glass Pasteur pipette; [0101]c) Store at 4° C.

2.3 Preparation of Phase Stocks--Lysate

[0101] [0102]a) Plate out phage-containing bacteria as described above and incubate for 24-48 h; [0103]b) Overlay plate with 5 ml SM buffer and leave for 1 h at room temperature with occasional swirling; [0104]c) Pipette buffer into a sterile tube (plastic universal or Falcon) then scrape top agarose off the plate into the tube; [0105]d) Centrifuge at >5000 rpm for 10 min at 4° C.; [0106]e) Remove supernatant and filter sterilise (0.2 μm filter); [0107]f) Aliquot and store at 4° C.

3. Host Phage Testing

[0108]3.1 Plating of P. acnes Bacteriophage [0109]a) Melt top agarose in a 70° C. water bath then cool to 44° C.; [0110]b) Centrifuge cultures of P. acnes at 5000 rpm for 10 min in a bench-top centrifuge; [0111]c) Resuspend cells to an OD₆₀₀ of 2.5 in SM buffer; [0112]d) Add 100 μl of P. acnes to an aliquot of phage (usually 5-10 μl) in a microcentrifuge tube, briefly mix and then incubate at 34° C. for 15 min; [0113]e) Gently pipette the P. acnes/phage mixture into 3 ml top agarose and invert to mix; [0114]f) Pour onto a dry RCA plate and swirl to cover surface; [0115]g) Allow to set and incubate anaerobically at 34° C. for 24-48 h.3.2 P. acnes Bacteriophage Infectivity Assay [0116]a) Melt top agarose in a 70° C. water bath then cool to 44° C.; [0117]b) Centrifuge cultures of P. acnes at 5000 rpm for 10 min in a bench-top centrifuge; [0118]c) Resuspend cells to an OD₆₀₀ of 2.5 in SM buffer; [0119]d) Add 100 μl of P. acnes to 3 ml top agarose and shake to mix; [0120]e) Pour onto a dry RCA plate and swirl to cover surface; [0121]f) Allow agarose to set then dry plate again for 15-20 min; [0122]g) Spot 5 μl of each phage onto the plate; [0123]h) Allow spots to soak in and incubate anaerobically at 34° C. for 48 h.

[0124]For high throughput screening of phage a multipoint inoculator can be used to apply phage spots to the surface of the plate.

3.3 Infectivity Assay of Bacteriophage Against Other Non-P. acnes Species

[0125]The bacteriophage strains were also tested against other species of bacteria, using the method outlined above but substituting other species for P. acnes. The species of bacteria tested were Propionibacterium granulosum, Propionibacterium avidum, Staphylococcus epidermidis and Corynebacterium bovis.

3.4 Infectivity Assay of Bacteriophage 103672 on P. acnes Immediately after Isolation from Skin of a Volunteer

[0126]Natural P. acnes numbers on the volunteer's back were known to be approximately 10⁶ cfu cm^-2 ("cfu" denotes "colony forming units"). A scrub wash sample was taken from the back of the volunteer as set out in Method 2.1 above. A small aliquot was taken to determine the starting P. acnes count (10⁵ cfu cm^-2). The rest of the sample was diluted 1:2 in 2×TYG broth (1× final TYG concentration) in order to grow the P. acnes. This was then further diluted in TYG to give 10-fold dilutions ranging from neat to 10^-3. Two samples of each dilution were aliquoted, phage 103672 added to one (10⁶ pfu ml^-1 final concentration, "pfu" denoting "plaque forming units") at a ratio of 6:1 phage:cell and SM added to the other as a control. These were then incubated anaerobically at 34° C. for 48 h.

[0127]Following incubation, each sample was diluted 10-fold from neat to 10^-2, filtered and treated with 10 mM ferrous ammonium sulphate (FAS), a compound which can inactivate free phage and which, in this context, is used to prevent carry-over of free (phage, which could give a false positive result. Filters were plated on RCA+furazolidone plates (RCAF) and incubated anaerobically at 34° C. for 6 days. At the end of this period, the number of colony forming units for cm³ was determined, by counting the number of colonies on the filter and using this figure to calculate the cfu in the original, undiluted, sample.

4. Identification of Non-Lysogenic P. acnes Bacteriophage

[0128]Bacteriophage were subjected to lysogeny and super-infection immunity testing as follows. Phage were spotted onto lawns of P. acnes AT1 to produce plaques and these were incubated for periods of time sufficient to allow growth of bacteria within plaques, such bacteria having developed resistance to phage infection. Resistance can develop through changes on the surface of the bacterial cell (e.g. receptor) or internally (e.g. restriction enzymes). However, lysogeny confers resistance to related phages in a process called "superinfection immunity". Repressor protein, expressed by the lysogen, prevents the integrated phage from synthesising the proteins necessary for reproduction. Repressor protein fulfils exactly the same function upon any homologous phage DNA coming into the cell, similarly preventing the production of phage. This can only happen if the incoming DNA is related to the lysogen such that the repressor can bind.

[0129]The centres of the turbid plaques were picked and streaked out to obtain single colonies of bacteria apparently resistant to infection by the phage, which may or may not have been lysogenic. At this stage, there was no way of knowing which mechanism of resistance, discussed above, had been acquired. Single colonies were picked and grown in tryptone/yeast extract/glucose (TYG) broth before plating as lawns in top agarose on reinforced clostridial agar (RCA) plates. First, spontaneous plaque formation was identified, indicating phage lysogeny as the result of earlier infection with a lysogenic phage. Second, phage were spotted onto the lawns to look for super-infection immunity to the same or other phage, an indication of lysogeny and/or resistance, since a plaque will form unless the bacteria are immune to infection by the particular phage. As outlined above, if they are immune to repeat infection by the same phage isolate, this suggests the presence of that phage in lysogenic phase in the cell. Similarly, if they are immune to infection by another phage isolate, this (suggests the presence of the first phage in lysogenic phase in the cell. Phage which do not display such lysogenic qualities are considered to be suitable for use in embodiments of the invention.

[0130]Alternative methods of identifying whether a phage can become lysogenic are PCR detection using primers specific to, for example, the phage repressor DNA, where a positive PCR result would indicate the presence of phage repressor DNA and, therefore, that the bacteriophage in question had the ability to become lysogenic. Absence of a repressor gene is one way of avoiding lysogeny, but other deletions which would convert a lysogenic phage into a lytic phage would include any that removes other parts of the integration machinery, i.e. phage-encoded integrase proteins and DNA sequences required for insertion into host DNA (att sites). Any sort of error which inactivates these genes or sites will achieve the desired lytic phage phenotype, such as entire or partial removal of the gene/site and functionally inactivating point mutation(s). Alternatively, a PCR-based method could detect the ligated cos site in cells which have been exposed to a bacteriophage of interest. Another method would be Southern blotting using labelled phage DNA to probe lysogens in the bacterial genome. These and other such methods are easily within the ability of the skilled person, who would clearly understand how to approach such methods in order to reliably identify whether a phage can become lysogenic and whether, therefore, it falls within the scope of the present invention.

5. DNA Sequencing

[0131]Bacteriophage DNA was extracted and purified using the following method: [0132]a) Prepare a plate lysate of the phage (10 ml) [0133]b) Add NaCl to 1 M and PEG8000 to 10% (w/v) and dissolve slowly [0134]c) Incubate on ice for 30 min to allow phage to precipitate [0135]d) Harvest phage by centrifuging at 10,000 g for 10 min at 4° C. [0136]e) Resuspend in 1 ml SM buffer [0137]f) Add an equal volume of chloroform and vortex for 30 sec [0138]g) Centrifuge at 3000 g for 15 min at 4° C. [0139]h) Remove the upper layer containing phage to a sterile tube [0140]i) Add proteinase K to 50 μg ml^-1 and SDS to 0.5% (w/v) and incubate at 56° C. for 1 hour [0141]j) Cool, then extract twice with phenol:chloroform and once with chloroform [0142]k) Precipitate DNA with 2 volumes of ethanol [0143]l) Transfer DNA to 1 ml 70% (v/v) ethanol using a Pasteur pipette [0144]m) Recover DNA by centrifugation at 12,000 g for 2 min, discard supernatant and redissolve the DNA in TE buffer or dH₂O

[0145]Sequencing was carried out by Lark Technologies Inc. (Houston, Tex.). PA6, 103609, 103672 and 1894 DNA was prepared as above and then used to prepare a shotgun library from which clones were sequenced to derive the full genome sequence for each bacteriophage.

6. ORF Analysis

[0146]Open reading frames (ORF) in several bacteriophage isolates were analysed using software available through GeneMark®, a family of gene prediction programs provided by Mark Borodovsky's Bioinformatics Group at the Georgia Institute of Technology, Atlanta, Ga. The ORF analysis tool there uses a heuristic approach to identifying possible genes using a computational method described in: Besemer J. and Borodovsky M. (1999) Nucl. Acids Res. 27: 3911-3920. The program can be found on the Internet at: http://opal.biology.gatech.edu/GeneMark/heuristic_hmm2.cgi

[0147]Gene product functions were determined by database comparison using the Blast analysis tool at http://www.ncbi.nlm.nih.gov/BLAST/.

Results

[0148]I. Testing of Bacteriophage Against Stock P. acnes Strains

[0149]A collection of 46 independent bacteriophage isolates were tested against a panel of 21P. acnes strains chosen for their diversity in age, origin and drug resistance profiles (listed in Table 1).

TABLE-US-00001 TABLE 1 List of strains used in bacteriophage host range screening tests. Strain number Bacterial isolate 1 P37 2 AT1 3 NCTC737 4 PF276 5 PF286 6 P506 7 CavillA 8 CavillB 9 AT4 10 AT5 11 101842c 12 101845a 13 101845b 14 101846c 15 101847a 16 101848 17 101849 18 101850a 19 101850b 20 101851a 21 DSM16379

[0150]The ability of each bacteriophage to lyse each bacterial strain was tested to give an indication of the breadth of host specificity of each phage. The results in Table 2 show that, in general, all phages had broad specificity. Of these, 14 were able to infect all strains tested: PA6, 103609, 103625, 103629, 103664, 103672, 103715, 1869, 1874, 1878, 1894, 1905, 1909 and P37P.

TABLE-US-00002 TABLE 2 Summary of results from bacteriophage host range testing. Phage P. acnes strain Isolate 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 PA6 + + + + + + + + + + + + + + + + + + + + + 103205 - + + - + + + + + + + + + + - + + + + + 103600 - + + - + + + + + + + + + + + + + + + + 103601 - + + - + + + + + + + + + + + + + + + + 103609 + + + + + + + + + + + + + + + + + + + + + 103611 + + + + + + + + + + + + + + + + + + + + - 103614 + + + - + + + + + + + + + + - + + + + + 103625 + + + + + + + + + + + + + + + + + + + + + 103629 + + + + + + + + + + + + + + + + + + + + + 103657 - + + - + + + + - + + + + + + + + + + + 103664 + + + + + + + + + + + + + + + + + + + + + 103666 + + + + + + + + + + + + + + + + + + + + - 103671 + + + + + + + + + + + + + + + + + + + + - 103672 + + + + + + + + + + + + + + + + + + + + + 103683 + + + + + + + + + + + + + + + + + + + + - 103695 + + + + + + + + + + + + + + + + + + + + - 103698 - + + - + + + + - + + + + + - + + + + + 103704 + + + + + + + + + + + + + + + + + + + + - 103713 + + + + + + + + + + + + + + + + + + + + - 103715 + + + + + + + + + + + + + + + + + + + + + 138 - + + + + + + + + + + + + + + + + + + + 139 - + + - + + + + + + + + + + - + + + + + 140 - + + - + + + + - + + + + + - + + + + + 1869 + + + + + + + + + + + + + + + + + + + + + 1874 + + + + + + + + + + + + + + + + + + + + + 1877 - + + - + + + + + + + + + + - + + + + + 1878 + + + + + + + + + + + + + + + + + + + + + 1880 - + + - + + + + + + + + + + - + + + + + 1881 - + + - + + + + - + + + + + - + + + + + 1883 - + + - + + + + + + + + + + - + + + + + 1885 + + + + + + + + + + + + + + + + + + + + - 1888 - + + - + + + + + + + + + + - + + + + + 1894 + + + + + + + + + + + + + + + + + + + + + 1895 - + + + + + + + + + + + + + - + + + + + 1900 - + + - + + + + + + + + + + + + + + + + 1901 - + + - + + + + - + + + + + - + + + + + 1902 - + + - + + + + + + + + + + - + + + + + 1905 + + + + + + + + + + + + + + + + + + + + + 1909 + + + + + + + + + + + + + + + + + + + + + 1922 - + + - + + + + + + + + + + - + + + + + 1923 - + + - + + + + + + + + + + - + + + + + 1925 + + + + + + + + + + + + + + + + + + + + - 1928 - + + - + + + + + + + + + + - + + + + + 1929 - + + - + + + + + + + + + + - + + + + + P37P + + + + + + + + + + + + + + + + + + + + + "+" denotes a positive reaction where bacteriophage is able to infect the host after applying neat phage stock to a seeded lawn of host bacteria in agar overlay. "-" denotes a negative reaction where no infection was evident.

[0151]None of these strains showed an ability to infect the P. granulosum, P. avidum, S. epidermidis and C. bovis species tested.

II. Testing of bacteriophage PA6, 103609, 103625, 103629, 103664, 103672, 103715, 1869, 1874, 1878, 1894, 1905, 1909 and P37P Against P. acnes Isolated from Volunteers' Skin

[0152]The 14 strains, shown above to have broad specificity, were further tested against 31 additional P. acnes strains, isolated from the skin of volunteers. The bacteriophage all showed lytic activity against these additional strains, as shown in Table 3:

TABLE-US-00003 TABLE 3 Summary of results from bacteriophage host range testing. Phage isolate 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 PA6 + + + + + + + + + + + + + + + + P37P + + + + + + + + + + + + + + + + 1869 + + + + + + + + + + + + + + + + 1874 + + + + + + + + + + + + + + + + 1878 + + + + + + + + + + + + + + + + 1894 + + + + + + + + + + + + + + + + 1905 + + + + + + + + + + + + + + + + 1909 + + + + + + + + + + + + + + + + 103609 + + + + + + + + + + + + + + + + 103625 + + + + + + + + + + + + + + + + 103629 + + + + + + + + + + + + + + + + 103664 + + + + + + + + + + + + + + + + 103672 + + + + + + + + + + + + + + + + 103715 + + + + + + + + + + + + + + + + Phage isolate 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 PA6 + + + + + + + + + + + + + + + P37P + + + + + + + + + + + + + + + 1869 + + + + + + + + + + + + + + + 1874 + + + + + + + + + + + + + + + 1878 + + + + + + + + + + + + + + + 1894 + + + + + + + + + + + + + + + 1905 + + + + + + + + + + + + + + + 1909 + + + + + + + + + + + + + + + 103609 + + + + + + + + + + + + + + + 103625 + + + + + + + + + + + + + + + 103629 + + + + + + + + + + + + + + + 103664 + + + + + + + + + + + + + + + 103672 + + + + + + + + + + + + + + + 103715 + + + + + + + + + + + + + + + "+" denotes a positive reaction where bacteriophage is able to infect the host after applying neat phage stock to a seeded lawn of host bacteria in agar overlay. "-" denotes a negative reaction where no infection was evident.

III. Identification of Non-Lysogenic P. acnes Bacteriophage

[0153]Phage were screened for lysogenic activity as outlined in Method 4 above. Three of the broad host range phage listed in Table 3 above showed no evidence of lysogeny or resistance in these experiments, as outlined in Method 4 above, with results shown in Table 4. They were phages 1894, 103609 and 103672.

TABLE-US-00004 TABLE 4 Data from repeated attempts to demonstrate lysogenic potential in phage. Phage infections (left column) of P. acnes strain AT1 were incubated for prolonged periods such that growth was visible within plaques. These emergent bacteria were sampled and tested for their susceptibility to infection with homologous or heterologous phage (top row). Potential Phage spotted onto lawn - plaque (infection) present? Lysogen PA6 P37P 1869 1874 1878 1894 1905 1909 103609 103625 103629 103664 103672 103715 PA6 N N N N N Y N Y Y N N N Y N P37P N N N N N Y N Y Y N N N Y N 1869 Y Y Y Y Y Y Y Y Y Y Y Y Y Y 1874 Y Y N Y Y Y Y Y Y Y Y Y Y Y 1878 N N Y N N Y N Y Y N N N Y N 1894 Y Y Y Y Y Y Y Y Y Y Y Y Y Y 1905 N N N N N Y N Y Y N N N Y N 1909 N N N N N Y N N Y N N N Y N 103609 Y Y Y Y Y Y Y Y Y Y Y Y Y Y 103625 N Y N N Y Y Y Y Y Y Y Y Y N 103629 N Y N N N Y N N Y N N N Y N 103664 N Y N N N Y N Y Y N N Y Y N 103672 Y Y Y Y Y Y Y Y Y Y Y Y Y Y 103715 N Y N N N Y Y Y Y N Y Y Y N `N` indicates resistance and therefore demonstration of lysogenic activity. Three strains 1894, 103609 and 103672 (underlined) failed to demonstrate lysogenic activity.

IV. DNA Sequencing

[0154]The genome for each of bacteriophages PA6, 103609, 103672 and 1894 was sequenced as outlined in Method 5 above. The sequences for each are shown in SEQ ID NO:1 (PA6), SEQ ID NO:3 (103609), SEQ ID NO:4 (103672) and SEQ ID NO:5 (1894).

V. ORF Analysis of Bacteriophage Genomes

[0155]Analysis of open reading frames (ORF) within the PA6 genome and subsequent analysis of predicted protein sequences using the Blast database analysis tool identified various potential genes and highlighted possible functions (summary of analysis shown in FIG. 1). The 5' end of the phage genome appears to host many of the structural genes which comprise the phage coat and tail. Notable among the remaining genes is a potential lysin (ORF 20) which shares homology with other lysins and an amidase protein within the P. acnes genome itself. The DNA sequence of this gene is shown in SEQ ID NO:2 and can be seen at nucleotides 15371-16233 of SEQ ID NO:1.

[0156]A similar analysis was carried out for the genomes of 103609, 103672 and 1894, with the summary shown in FIG. 2 (103609), FIG. 3 (103672), FIG. 4 (1894) and Table 5. Again, ORF 20 in each case encodes a potential lysin. The DNA sequence for this gene is shown in SEQ ID NO: 6 (phage 103609, nucleotides 15442-16296 of SEQ ID NO: 3), SEQ ID NO:7 (phage 103672, nucleotides 15382-16245 of SEQ ID NO: 4) and SEQ ID NO:8 (phage 1894, nucleotides 15416-16273 of SEQ ID NO: 5). The boundaries for each ORF for each bacteriophage strain are shown in Table 5. No repressor protein is obvious from sequence homology analysis in these phage strains and this is an indication that these are purely lytic phage, unable to sustain lysogeny, as supported by the results shown in Table 4. Therefore, this confirms that these phage strains are ideal in this respect as candidates for phage therapy.

TABLE-US-00005 TABLE 5 ORF boundaries for phage 103609, 103672 and 1894 1894 ORFs (30 total) 103609 ORFs (32 total) 103672 ORFs (32 total) ORF 1 Start: 53 End: 361 ORF 1 Start: 145 End: 363 ORF 1 Start: 113 End: 361 ORF 2 Start: 361 End: 1872 ORF 2 Start: 363 End: 1874 ORF 2 Start: 361 End: 1872 ORF 3 Start: 1869 End: 3194 ORF 3 Start: 1871 End: 3196 ORF 3 Start: 1869 End: 3194 ORF 4 Start: 3201 End: 3956 ORF 4 Start: 3203 End: 3958 ORF 4 Start: 3198 End: 3953 ORF 5 Start: 4067 End: 4621 ORF 5 Start: 4069 End: 4629 ORF 5 Start: 4057 End: 4611 ORF 6 Start: 4628 End: 5575 ORF 6 Start: 4636 End: 5583 ORF 6 Start: 4618 End: 5565 ORF 7 Start: 5620 End: 6081 ORF 7 Start: 5627 End: 6088 ORF 7 Start: 5613 End: 6074 ORF 8 Start: 6083 End: 6430 ORF 8 Start: 6090 End: 6437 ORF 8 Start: 6076 End: 6422 ORF 9 Start: 6437 End: 6727 ORF 9 Start: 6444 End: 6734 ORF 9 Start: 6430 End: 6720 ORF 10 Start: 6724 End: 7095 ORF 10 Start: 6731 End: 7102 ORF 10 Start: 6717 End: 7087 ORF 11 Start: 7147 End: 7776 ORF 11 Start: 7154 End: 7795 ORF 11 Start: 7140 End: 7769 ORF 12 Start: 7803 End: 8099 ORF 12 Start: 7824 End: 8120 ORF 12 Start: 7797 End: 8093 ORF 13 Start: 8198 End: 8485 ORF 13 Start: 8219 End: 8506 ORF 13 Start: 8192 End: 8479 ORF 14 Start: 8493 End: 11258 ORF 14 Start: 8514 End: 11279 ORF 14 Start: 8487 End: 11252 ORF 15 Start: 11274 End: 12215 ORF 15 Start: 11295 End: 12236 ORF 15 Start: 11270 End: 12211 ORF 16 Start: 12223 End: 13380 ORF 16 Start: 12244 End: 13401 ORF 16 Start: 12219 End: 13376 ORF 17 Start: 13430 End: 14218 ORF 17 Start: 13451 End: 14239 ORF 17 Start: 13425 End: 14213 ORF 18 Start: 14299 End: 14538 ORF 18 Start: 14296 End: 14559 ORF 18 Start: 14259 End: 14522 ORF 19 Start: 14541 End: 15374 ORF 19 Start: 14563 End: 15387 ORF 19 Start: 14525 End: 15340 ORF 20 Start: 15416 End: 16273 ORF 20 Start: 15442 End: 16296 ORF 20 Start: 15382 End: 16245 ORF 21 Start: 16286 End: 16684 ORF 21 Start: 16309 End: 16707 ORF 21 Start: 16258 End: 16656 ORF 22 Start: 19047 End: 19103 ORF 22 Start: 20662 End: 20766 ORF 22 Start: 18710 End: 18955 ORF 23 Start: 23248 End: 23391 ORF 23 Start: 20767 End: 20919 ORF 23 Start: 19393 End: 19497 ORF 24 Start: 24869 End: 25012 ORF 24 Start: 23272 End: 23415 ORF 24 Start: 19946 End: 20044 ORF 25 Start: 25760 End: 25810 ORF 25 Start: 24093 End: 24293 ORF 25 Start: 23239 End: 23382 ORF 26 Start: 27128 End: 27172 (-) ORF 26 Start: 24899 End: 25042 ORF 26 Start: 24863 End: 25006 ORF 27 Start: 27340 End: 27582 (-) ORF 27 Start: 27152 End: 27196 (-) ORF 27 Start: 27006 End: 27164 ORF 28 Start: 27586 End: 27708 (-) ORF 28 Start: 27326 End: 27583 (-) ORF 28 Start: 27268 End: 27522 (-) ORF 29 Start: 27721 End: 27888 ORF 29 Start: 27593 End: 27715 (-) ORF 29 Start: 28059 End: 28133 (-) ORF 30 Start: 28743 End: 29108 (-) ORF 30 Start: 28126 End: 28200 (-) ORF 30 Start: 28424 End: 28465 (-) ORF 31 Start: 28528 End: 28569 (-) ORF 31 Start: 28534 End: 28683 (-) ORF 32 Start: 28891 End: 29274 (-) ORF 32 Start: 28779 End: 29153 (-) (-) indicates that the ORF is coded on the reverse DNA strand

[0157]The % sequence identity of the DNA sequences in the ORFs between the three bacteriophage is shown in Table 6:

TABLE-US-00006 TABLE 6 % sequence identity of each ORF between the three phage 103609, 103672 & 1894; ORF Identity (%) 1 62.7* 2 90.3 3 90.0 4 90.0 5 88.6 6 91.9 7 95.2 8 93.1 9 94.8 10 90.8 11 92.5 12 96.3 13 98.6 14 90.1 15 92.7 16 93.5 17 96.5 18 66.9 19 79.7 20 87.4 21 85.2 22 96.4 23 97.2 24 92.3 25 86.0 26 62.2 27 79.8 28 77.9 29 65.9 30 86.8 31 -- 32 -- *ORF1 for 1894 is over 100 nucleotides longer than for either 103609 or 103672.

[0158]FIG. 5 shows the outcome of a sequence homology analysis between 103609, 103672 and 1894, in which similarity level of 1.0 indicates 100% identity, with similarity falling according to the nature and number of differences between the three sequences. This analysis demonstrates that overall sequence identity between all of these three phage is 86.1%.

[0159]FIG. 6 shows the results of a similar analysis between these three phage and PA6, a bacteriophage which does not show the desired characteristic of being incapable of sustaining lysogeny in a bacterium (see results Section III above). This analysis demonstrates that overall sequence identity between all of these four phage is 80.1%. Overall sequence identity between 1894 and PA6 is 87.4%, between 103609 and PA6 is 86.8% and between 103672 and PA6 is 87.3%.

[0160]FIG. 6 clearly shows that there are two regions of low or zero % sequence identity when the DNA sequences of the three phage 103609, 103672 and 1894 are compared to that of PA6. FIGS. 7 and 8 show that this is the result of the presence of nucleotide sequences in PA6 which are not present in any of the other three phage.

[0161]Referring to nucleotide sequence numbering according to that shown in FIGS. 7 and 8, nucleotides 19804-10843 of PA6 are shown as SEQ ID NO: 9; nucleotides 19876-19901 of PA6 are shown as SEQ ID NO:10; nucleotides 19913-19969 of PA6 are shown as SEQ ID NO:11; nucleotides 19979-20054 of PA6 are shown as SEQ ID NO:12; and nucleotides 26242-26620 of PA6 are shown as SEQ ID NO:13.

[0162]Without wishing to be bound by theory, although these DNA inserts are present in PA6 in non-ORF regions of the genome, the presence of such large additional DNA inserts could have an effect on the overall structure of the genome and could affect, for example, the efficacy of expression of the ORF regions.

VI. Utilising Bacteriophage 103672 as an Anti-P. acnes Treatment

[0163]Bacteriophage 103672 was tested against P. acnes bacteria immediately after isolation of the bacteria from a volunteer's skin, as outlined in Method 3.4 above. The results are as shown in Table 7:

TABLE-US-00007 TABLE 7 Results of incubation of P. acnes isolated from the skin of a volunteer, in the absence or presence of bacteriophage 103672 Initial propionibacterial Final count, Final count, count, cfu ml^-1 cfu cm^-2 cfu cm^-2 (Phage:cell ratio) (control) (+103672) 1.585 × 10⁵ (6:1) Too much 0 growth to quantify

[0164]This clearly shows the efficacy of the bacteriophage against P. acnes directly isolated from the skin of the patients and demonstrates the usefulness of such bacteriophage as an anti-P. acnes agent, whether directly within a method of treatment of acne or as an ingredient in a medicament for use in such a method.

Sequence CWU 1

13129739DNABacteriophage PA6 1agtgaaatac ctcccttttg tggttttgtc tgtttgtcga ctttttgtgt tggtggtgag 60tgttgtgcag cctgagcttc ctgagtctcg tgagtggtgt ggggagacgc gtcgttggtg 120gcgtgtgtgg ggtgaggata gtcgcgcgcc gtatgtgtct gatgaggagt ggttgtttct 180tatggatgct gcggtgattc atgattgtgt gtggcgtgag ggtcgcgcgg atttggtggc 240ttcgcttcgt gcgcatgtga aggcttttat gggcatgttg gataggtatt cggttgatgt 300ggcgtctggt ggccgtggtg ggggttctgc tgtggcgatg attgaccggt ataggaagcg 360taggggggct tgagtaggtg tctggtgttg ttgggtctca ggttcctcgt caccgtgtgg 420ctgcggcgta ttcggtgtct gctgggggtg atgctgggga gcttggtcgt gcgtatgggt 480tgacgcctga tccgtggcag cagcaggtgt tggatgattg gctggctgtc ggtagcaatg 540gcaggcttgc ttctggtgtg tgtggggtgt ttgttccgcg gcagaatggc aagaatgcta 600ttttggagat tgtggagttg tttaaggcga ctattcaggg tcgccgtatt ttgcatacgg 660ctcacgagtt gaagtcggct cgtaaggcgt ttatgcggtt gaggtcgttt tttgagaatg 720agcggcagtt tcctgacttg tatcgtatgg tgaagtcgat tcgtgcgacg aatggtcagg 780aggctattgt gttgcatcat ccggattgtg ccacttttga gaagaagtgt ggctgcagcg 840gttggggttc ggttgagttt gtggctcgta gccggggttc ggctcgcggg tttacggttg 900atgatttggt gtgtgatgag gctcaggagt tgtcggatga gcagttggag gctttgcttc 960ctacggtaag tgctgccccg tctggtgatc cgcagcagat tttccttggt acgccgcctg 1020ggccgttggc tgatggttct gtggtgttgc gtttgcgtgg gcaggcgctt ggtggcggta 1080aaaggtttgc gtggacggag ttttcgattc ctgacgagtc tgatccggat gatgtgtcgc 1140ggcagtggcg gaagttggcg ggggatacga atccggcgtt ggggcgtcgc ctgaattttg 1200ggaccgtaag cgatgagcat gagtcgatgt ctgctgccgg ttttgctcgg gagcggcttg 1260gctggtggga tcgtggccag tctgctgcgt ctgtggttcc tgctgataag tgggctcagt 1320ctgcggtgga tgaggcgagt ctggttggcg ggaaagtgtt tggtgtctcg ttttctcgtt 1380ctggggatcg ggttgctttg gcgggtgccg gcaagactga tgctggggtt catgttgagg 1440ttattgatgg gctgtcggga acgattgttg atggtgtggg ccggttggct gactggttgg 1500cggttcgttg gggtgatact gaccggatca tggttgccgg gtctggtgcg gtgttgttgc 1560agaaggcgtt gacggatcgt ggtattccgg gccgtggcgt ggtggttgct gatactggcg 1620tttatgtgga ggcttgtcag gcgtttcttg agggtgtcag gtcgggtgtg atcagtcatc 1680ctcgtgctga ttctcgccgt gacatgttgg atattgctgt gaggtcggct gtgcagaagc 1740gtaaggggtc tgcgtggggt tggggttcct cgtttaagga tggttctgag gttcctttgg 1800aggctgtgtc tttggcgttt ttgggggcta aacgtgttcg tcgtggccgt cgggagcgta 1860gtggtaggaa gcgggtgtct gtggtatgaa ctcggatgag ttggctctga ttgagggcat 1920gtacgatcgt atccaaaggt tgtcttcgtg gcattgttgt attgagggct actatgaggg 1980ctctaatcgg gtgcgtgacc ttggtgtggc tattccgccg gagttgcagc gtgtgcagac 2040tgtggtgtcg tggcctggta tagctgtgga tgctttggag gagcgtctgg attggcttgg 2100ctggactaat ggtgacggct acggccttga tggtgtgtat gctgcgaatc ggcttgctac 2160ggcgtcgtgt gatgtgcatt tggatgcgct gatttttggg ttgtcgtttg ttgcgatcat 2220tcctcatggt gatggtacgg tgtcggttcg tccgcagtca ccaaagaatt gtacgggcaa 2280gttttcggct gacgggtctc gtttggatgc gggtttggtg gtgcagcaga cgtgtgatcc 2340tgaggttgtt gaggctgagc ttttgcttcc tgatgtgatt gttcaggtgg agcggcgggg 2400ttcgcgtgaa tgggttgagg tggatcgtat accgaatgtg ttgggtgcgg ttccgttggt 2460gcctattgtg aatcgtcgcc gtacttctag gattgatggc cgttcggaga ttacgaggtc 2520tattagggct tacacggatg aggctgtgcg cacactgttg gggcagtctg tgaatcgtga 2580tttttatgcg tatcctcagc gttgggtgac tggcgtgagc gcggatgagt tttcgcagcc 2640tggctgggtc ctgtcgatgg cttctgtgtg ggctgtggat aaggatgatg acggtgacac 2700tccgaatgtg gggtcgtttc ctgtcaatag tcctacaccg tattcggatc agatgagact 2760gttggcgcag ttgactgcgg gtgaggcggc tgttccggaa cgctatttcg ggtttatcac 2820gtctaaccca cctagtgggg aggctttggc tgccgaggaa tctcggcttg tgaagcgtgc 2880tgagcggcgt caaacgtcgt ttggtcaggg ttggctgtcg gttggttttt tggctgccaa 2940ggcgttggat tctcgtgttg atgaggccga tttttttggt gatgttggtt tgcgttggcg 3000tgatgcttcg acgcctaccc gggcggctac ggctgatgct gtgacgaagc ttgttggtgc 3060cggtattttg cctgctgatt ctcgtacggt gttggagatg ttggggcttg atgatgtgca 3120ggttgaggct gtgatgcgtc atcgtgctga gtcgtctgac ccgttggcgg tgcttgctgg 3180ggctatatcg cgtcaaacta acgaggtatg ataggcgatg gcttcggggg ttgaggcgag 3240gcttgcggcg actgagtatc agcgtgaggc ggtcaggttt gctgggaagt atgcgggcta 3300ttattctgag cttggtcgtt tgtggcgtgc cggcaggatg agtgacacgc agtatgtgcg 3360tttgtgtgtg gagttggagc gtgccggcca tgatggttcg gcatcgttgg ctgccaggtt 3420tgtgtcggat tttcgccggt tgaatggtgt ggatccgggt ttgattgtgt atgacgagtt 3480tgatgctgcg gcggctttgg ctaggtctat ttcgaccacg aagattcttg agagtgaccc 3540ggatagggcg aatgacacga ttgatgcgat ggcggcgggt tttgatcggg ctgttatgaa 3600tgctggccgt gacacggttg agtggtctgc gggtgcgcag ggtaggtcgt ggcgtcgggt 3660gacggatggt gatccgtgtg ctttttgtgc catgttggct acgaggtcgg attatacgac 3720aaaagagagg gcacttacta ctggacatac tcggcgtcat aagcgtggtg gtaagcgtcc 3780gtttggttcg aagtatcatg atcattgtgg ttgtacggtg gttgaggttg ttggcccttg 3840ggaaccaaat agggctgatg ccgagtatca gaggacgtat gagaaggcct gtgagtgggt 3900tgatgatcat gggttgcagc aatcgcctgg caatattttg aaggctatgc gtactgttgg 3960cgacatgaga taatttgatg tggtttccgg ttgtgcgccg ccggttattg gtgcacaggg 4020ttgtctcccg cacgggggtc aacaatattg tgttgttttc cgcaaggagt gtagggttag 4080gctatggccg atcagagtgt tgaggaacag aatgttgaca atgatgttgt ggagtccgga 4140aaggataacg gcattgttga tacagtaaaa gacgatggcg ggcaggaggt agccgacaat 4200cagttgaaga atgaaggcga gggtaaatcg ccggggactg attggaaggc tgaggcccgt 4260aagtgggagt ctcgtgctaa aagtaatttt gccgagttgg agaagcttcg cgcctcggat 4320ggtgatgcgg ggtctacgat tgatgagctt cgccgcaaga atgaggaact cgaagaccgg 4380atcaatgggt ttgttcttga gggtgtgaag cgcgaggtgg ctgccgagtg tggcctgtcg 4440ggtgatgctg tcgctttctt gtcgggtggc gataaggagt cgcttgccga gtctgcgaaa 4500gctttgaagg gtttgatcga ccatagtagt ggtggcgcgg gtgtgcgccg tcttgcgggg 4560agtgcccccg ttgatgatgt taaacgacgt gagggtgtcg cgtttgtgga tgctcttgtc 4620aataattcta ggagatgatt tgtgatggct gacgattttc tttctgcagg gaagcttgag 4680cttcctggtt ctatgattgg tgcggttcgt gaccgtgcta tcgattctgg tgttttggcg 4740aagctttcgc cggagcagcc gactattttc gggcctgtga agggtgccgt gtttagtggt 4800gttcctcgcg ccaagattgt tggtgagggc gaggttaagc cttccgcgtc tgttgatgtt 4860tcggcgttta ctgcgcagcc tatcaaggtt gtgactcagc agcgtgtctc ggatgagttt 4920atgtgggctg atgctgatta ccgtctgggt gtgcttcagg atctgatttc cccggctctt 4980ggtgcttcga ttggtcgcgc cgtggatctg attgctttcc atggtattga tcctgccact 5040ggtaaagcgg cttccgctgt gcatacttcg ctgaataaga cgaagaatat tgttgatgcc 5100acggattctg ctacggctga tcttgttaag gctgtcggcc tgattgctgg tgctggtttg 5160caggttccta acggggttgc tttggatccg gcgttctcgt ttgcgctgtc tactgaggtg 5220tatccgaagg ggtctccgct tgccggtcag cctatgtatc ctgccgccgg gtttgccggt 5280ttggataatt ggcgcgggct gaatgttggt gcttcttcga ctgtttctgg cgccccggag 5340atgtcgcctg cctctggcgt taaggctatt gttggtgatt tctctcgtgt tcattggggt 5400ttccagcgta acttcccgat cgagcttatc gagtatggtg acccggatca gactgggcgt 5460gacttgaagg gccataatga ggttatggtt cgtgccgagg ctgtcctgta tgttgcgatt 5520gagtcgcttg attcgtttgc tgttgtgaag gagaaggctg ccccgaagcc taatccgccg 5580gccgagaact gattcatttg ttgcggtgat gttttctatg tgcagggggt ggtgttgatg 5640ggtatcattt tgaagcctga ggatattgag cctttcgccg atattcctag agagaagctt 5700gaggcgatga ttgccgatgt ggaggctgtg gctgtcagtg tcgccccctg tatcgctaaa 5760ccggatttca aatacaagga tgccgctaag gctattctgc gcagggccct gttgcgctgg 5820aatgataccg gggtttcggg tcaggtgcag tacgagtctg cgggcccgtt tgctcagact 5880acacggtcga atactcccac gaatttgttg tggccttctg agattgccgc gttgaagaag 5940ttgtgtgagg gtgatggtgg ggctggtaaa gcgttcacta ttacaccgac catgaggagt 6000agtgtgaatc attctgaggt gtgttccacg gtgtggggtg agggttgctc gtgcggatct 6060gatattaacg gctatgctgg ccctttgtgg gagatatgat atgaccggtt ttccttacgg 6120tgaaacggtt gtgatgcttc aaccgactgt tcgtgtcgat gatcttggcg acaaggtgga 6180agactggtct aagcctgtcg agactgtgta ccataacgtg gccatctatg cttccgtttc 6240gcaggaggat gaggctgccg gccgtgactc tgactatgag cattggtcga tgcttttcaa 6300gcagcctgtt gtgggtgccg gttatcgttg ccggtggcgt attcggggtg tggtttggga 6360ggcggacggg tctcctatcg tgtggcatca tccgatgtct ggttgggatg ctggtacgca 6420ggttaatgtg aagcgtaaga agggctgatg ggttgtggct caggatgtga atgtgaagct 6480gaacttgccg ggtattcgtg aggtgttgaa gtcttctggg gtgcagtcga tgttggctga 6540gcgtggcgag cgggtgaggc gtgcggcttc ggcgaatgtt ggcggtaatg cttttgatag 6600ggcccaatac cgtagtggtt tgtcgtcgga ggtgcaggtt caccgtgtgg aggctgtggc 6660gaggattggc accacctata agggtgggaa gcgtattgag gcgaagcatg gcacgttggc 6720gaggtcgatt ggggctgcgt cgtgatcgtt tacggtgatc cgcgtgtgtg ggctaaacgt 6780gtgctcaagg atgatggctg gctgtccgat ataccctgtg tggggacggt gcctgacgat 6840ttcagcggtg acctgatttg gttggcgttg gatggcggcc cacagttgca tgttcgcgag 6900caggtgtttt tgcgggtgaa cgtgttttct gatatgcctg atcgtgccat gtcgctagcc 6960aggcgggttg aggctgtcct tgtagacggt gtggacggtg acccggtggt gttttgtcga 7020cggtctactg gccctgattt gctggttgat ggtgcacgtt ttgatgtgta ttcgctgttt 7080gagctgatat gcaggcctgt cgaatccgag taaacgtttt gttttgatat tgttgtttgt 7140tttttgtttg atattgtttt tgggggttat gatggctgga acacgtaaag cgtctaatgt 7200tcgttccgcg gttacgggtg acgtctatat tggtaaagct catgccggtg acactattga 7260tggtgtgaag acggttcctg acgggcttac agctttaggg tatctgtctg atgacgggtt 7320taagattaaa ccggagcgta aaacggatga tttgaaggct tggcagaatg cggatgttgt 7380tcgcactgtg gctacggaat cgtctatcga gatttctttc cagctgatcg agtctaagaa 7440ggaggttatc gagctgtttt ggcagtcgaa ggttactgcc ggagccgatt cgggttcgtt 7500cgatatttct cctggtgcca cgacgggtgt tcatgccctg ttgatggata ttgttgatgg 7560cgatcaggtt attcgctact atttccctga ggttgagttg atcgatcgtg acgagattaa 7620gggtaagaat ggcgaggtgt atgggtatgg tgtgacgttg aaggcgtatc ctgcccagat 7680taataagaag ggtgatgcgg tgtctggtcg ggggtggatg acggctttaa aagctgatac 7740tcctccgact cctcctccgg ccccgaatcc tccgaagcct gagccggatc cgaatccgcc 7800gtctaataac tgatacacat agtttgaggg attgttgata gatgagtgac acgggttaca 7860cgttgaagat tggtgaccgt agctgggtgt tggcggatgc ggaggagacg gctcaggctg 7920ttcctgcccg cgttttccgt cgtgctgcta agattgccca gtcgggtgag tctgcggatt 7980tcgcccaggt tgaggtgatg ttttctatgt tggaggctgc cgccccggct gacgcggtgg 8040aggccctgga ggggcttcct atggttcgtg tggccgagat tttccgccag tggatggaat 8100acaagcctga cggtaagggt gcctcgctgg gggaatagtt tggctccacg gcctgattga 8160tgattatcgt ggggccatcg aatacgattt ccgcaccaag tttggtgttt ctgtttatag 8220tgttggtggc ccgcagatgt gttggggtga ggctgtccgg ctggctggcg tgttgtgtac 8280cgatacgtct agccagttgg cggcccacct gaatggttgg aagcgcccgt ttgagtggtg 8340cgagtgggct gtgttggaca tgctggatca ttacaggtct gctaatagtg aggggcagcc 8400ggagcctgtg gcgaggccta cggatgagcg tagggcccgg tttacgtctg ggcaggtgga 8460cgatattttg gcgcgtgttc gtgctggtgg cggggtgtct cgcgagatta atattatggg 8520gtgaatagtg tatgtctggt gagattgctt ccgcatatgt gtcgttgtat acgaagatgc 8580ctggtttgaa ggcggatgtt ggtaaacagc tttctggggt gatgcctgct gagggtcagc 8640gttcgggtag tttgtttgct aagggaatga agttggctct tggtggtgcg gcgatgatgg 8700gtgccatcaa tgttgctaag aagggcctca agtcgattta tgatgtgact attggtggcg 8760gtattgctag ggcgatggct attgatgagg ctcaggctaa gttgactggt ttgggtcata 8820cgtcttctga cacgtcttcg attatgaatt cggctattga ggctgttact ggtacgtcgt 8880atgcgttggg ggatgcggcg tctacggctg cggcgttgtc tgcttcgggt gtgaagtctg 8940gcgggcagat gacggatgtg ttgaagactg tcgccgatgt gtcttatatt tcgggtaagt 9000cgtttcagga tacgggcgct atttttacgt ctgtgatggc tcgcggtaag ttgcagggcg 9060atgacatgtt gcagcttact atggcgggtg ttcctgtcct gtctttgctt gccaggcaga 9120ctggtaaaac gtctgctgag gtgtcgcaga tggtgtcaaa ggggcagatt gattttaaca 9180cgtttgcggc tgcgatgaag cttggcatgg gtggtgctgc gcaggcgtct ggtaagacgt 9240ttgagggcgc tatgaagaat gttaagggcg ccctgggtta tcttggtgct acggctatgg 9300ccccgtttct taacgggttg cggcagattt ttgttgcgtt gaatccggtt atcaagtctg 9360tcacggattc cgtgaagccg atgtttgctg ccgtcgatgc tggtattcag cgtatgatgc 9420cgtctatttt ggcgtggatt aaccgtatgc cggctatgat cactcgaatg aatgcacaga 9480tgcgcgccaa ggtggagcag ttgaagggcg tttttgcaag gttgcatttg cctgttccta 9540aggtgaattt gggtgccatg tttgctggcg gcaccgcagt gttcggtatt gttgctgcgg 9600gtgttgggaa gcttgtcgcg gggtttgccc cgttggcggt gtcgttgaag aatctgttgc 9660cgtcgtttgg tgctttgagg ggtgccgccg gggggcttgg tggcgtgttt cgcgccttgg 9720gtggccctgt tggtattgtg atcggcttgt ttgctgccat gtttgctacg aacgcccagt 9780tccgtgccgc tgttatgcag cttgtggggg tggttggccg ggctttgggg cagattatgg 9840tcgccttgca gccattgttc gggattgttg ctggcgtggt tgccaggttg gctcccgttt 9900ttggccagat tattggtatg gttgctggtt tggctgcccg gctggtgcct gttattggta 9960tgcttattgc ccggctggtt cctgttatca cccagattat tggtatggta acccaggttg 10020ctgccatgtt gttgcctatg ctgatgccgg ttattcaggc tgttgttgct gtgatacggc 10080aggttattgg tgtggtcatg cagttgatac ctgttttgat gccggttgtg cagcagattt 10140tgggtgctgt catgtctgtt ttgccgccga ttgttggttt gatacggtcg ctgataccgg 10200tgatcatgtc gattatgcgt gtggtggtgc aggttgttgg tgccgtgcta caggtggtgg 10260cccgtattat tccggttgtt atgccgattt atgtttcggt gattggattc attgccaaga 10320tttatgctgc ggttatcgtt tttgaggcta aggttattgg cgctattctt cgtactatta 10380cgtggattgt gaatcattca gtgtctggcg tgaggtctat gggcacggcc atccagaatg 10440gctggaatca tatcaaatcg tttacgtcgg cgtttattaa cggtttcaag tcgatcattt 10500ctgccggtgt tgccgcggtt gtggggtttt ttacgcggct tggtttgtcg gttgcctccc 10560atgtgaggtc tggttttaac gcggcccgtg gtgctgtttc ttctgcgatg aatgctattc 10620ggagtgttgt gtcttcggtg gcgtctgctg ttggcgggtt tttcgggtcg atggcgtcta 10680gggttcgtag tggtgctgtg cgcgggttta atggtgcccg gagtgcggct tcttctgcta 10740tgcatgctat ggggtctgcg gtgtctaacg gtgtgcatgg tgtgctgggg tttttccgga 10800atttgcctgg caatattagg ggcgccttgg gtagtatggg gtccctgttg gtgtcggctg 10860gccgtgatgt ggtgtctggt ttgggtaacg gtatccggaa tgctttgagt ggcctgttgg 10920atacggtgcg taacatgggt tcccagattg cgaacgcggc gaagtctgcg ctgggtattc 10980attccccgtc tcgggtgttt cgtgacgagg ttggccgtca ggttgttgcc ggtttggctg 11040aggggatcac cgggaatgct ggtttggcgt tggatgcgat gtctggtgtg gctggccgtc 11100ttccggatgc tgtggatgcc cggtttggtg tgcgatcgtc tgtgggctcg tttaccccgt 11160acgaccggta tcggcgtgcg aacgagaaga gtgttgtggt gaatgtgaac ggacccacgt 11220atggggatcc tgccgagttt gcgaagcgga ttgagcgtca gcagcgtgac gctttgaatg 11280cgttggctta cgtgtgatcg agggggtgtt gtgcatgttt attcctgacc cgtctgatcg 11340tgccggtttg actgtggatt ggactatgtt tccgttggtg ggtaatgctc cggagcgtgt 11400gcttcatttg acggattata cggggtcgtc tccggtcatg ttgttgaatg attcgttgcg 11460cggcctgggt atgcctgagg tggagcagtt ttctcaaacg catgttggtg tgcatggttc 11520ggagtggcgc gggtttaatg tgaagcctcg cgaggtgact ttgccggtgt tggtgtcggg 11580tgttgacccg gatccggtgg gcgggtttcg tgacggtttt ttgaaggcgt atgacgcgtt 11640gtggtctgcg tttcctccgg gcgaggtggg ggagttgtct gtgaagactc ctgccggtcg 11700tgagcgtgtg ttgaagtgcc ggtttgattc ggctgatgac acgtttacgg ttgatccggt 11760gaaccgtggc tatgcgcgct atctgttgca tttgacagct tatgatccgt tttggtatgg 11820ggatgagcaa aagtttcgtt ttagtaacgc gaagttgcag gattggttgg gtggcggccc 11880tgtcggcaag aagggtaccg cgtttcctgt ggtgttaaca ccgggtgtgg gctcgggctg 11940ggataacctg tctaataagg gtgatgtgcc tgcgtggcct gtgattcgtg ttgagggtcc 12000tttggagtcg tggtctgtgc agattgatgg tttgcgtgtg tcttcggact atccggtcga 12060ggagtttgat tggatcacta ttgatacgga tcctcgccag cagtctgcgt tgttgaacgg 12120gtttgaggat gtgatggatc gtttgacaga gtgggagttt gcgcctatcc cgcctggcgg 12180ttctaagagt gtgaatattg agatggttgg tttgggtgct attgttgtgt cggtgcagta 12240caggtttttg agggcttggt gaatagttga tggctggtct tgttccgcat gtaacattgt 12300ttacacctga ttatcgccgt gtggcgccta tcaatttttt tgagtcgttg aagttgtcgt 12360tgaagtggaa tggtttgtcg actttggagt tggtggtgtc gggggatcat tcgaggcttg 12420acgggttgac gaagccgggt gcgcggctgg ttgttgatta tggtggtggc cagatttttt 12480ctgggcctgt gcgtaaagtg catggtgtgg gtccgtggcg ttcttcccgt gtgactataa 12540cgtgtgagga tgatattcgg ctgttgtggc gtatgttgat gtggcctgtg aattatcgtc 12600ctggtttggt tggtatggag tggcgtgcgg acagggatta tgcccactat tcgggtgcgg 12660ctgagtcggt tgctaagcag gtgttggggg ataatgcttg gcgttttccg cctggtttgt 12720ttatgaacga tgatgagagt cgtggccgct atattaagga ttttcaggtg cggtttcacg 12780tgtttgccga taagttgttg ccggtgttgt cgtgggctcg gatgactgtc acggtgaacc 12840agtttgagaa tgcgaagttt gatcagcgtg gtttgttgtt tgattgtgtg cctgctgtga 12900cccggacgca tgtgttgact gccgagtctg gttcgattgt gtcgtgggag tatgtgcgtg 12960acgccccgaa ggctacttcg gtggtggttg gtggccgcgg cgagggcaaa gatcggctgt 13020tttgcgagga tgttgattcg atggccgagg atgactggtt tgatcgtgtc gaggtgttta 13080aggatgcccg taacacggat tccgagaatg tgcatcttat tgatgaggct gagcgggtgt 13140tgtccgagtc gggggctacg tcggggttta agatcgagtt ggctgagtcg gatgtgttgc 13200ggtttgggcc tggccgcctg atgccgggtg atcttatcta tgtggatgtg ggctcggggc 13260ctattgcgga gattgtgcgc cagattgatg tggagtgtga ttcgcctggt gatgggtgga 13320cgaaggtgac tccggttgct ggggattatg aggataatcc gtcggcgctg ttggctcgcc 13380gtgtggctgg tttggctgcg ggtgtgcggg atttgcaaaa attctaattg ttaggggttt 13440gttgtgggta ttgtgtgtaa agggtttgat ggtgtgttga ccgagtatga ttgggctcaa 13500atgtctggtc tgatgggtaa tatgccgtcc gtgaaagggc cggatgattt tcgtgtcggc 13560actacgattc agggttccac ggtgttgtgt gaggtcctgc cggggcaggc ttgggctcac 13620ggggtgatgt gcacgtcgaa tgctgttgag acggtgacag gtcagcttcc gggcccgggt 13680gagacccgct acgactatgt tgtcctgtcg cgggattggc aggagaatac ggccaagttg 13740gagattgttc ctggggggcg tgcggagcgt gcccgtgacg tgttgcgtgc ggagcctggc 13800gtgtaccatc agcagttgtt ggctactttg gtggtgtcgt ctaacgggtt gcagcagcag 13860cttgacagga gggctatagc ggcccgtgtg gcgtttgggg agtctactgc atgtgatcct 13920acccctgtgg agggtgaccg ggtgatggtg ccttctgggg ctgtgttggc taatcatgct 13980aacgagtgga tgctgttgtc tccgcggatt gagacgggca ctaagtcgat catgtttggc 14040gggtctgctg tgtatgctta cacgattccg tttgatcgcc agtttgctag tccgcctgtt 14100gtggtggcgt ctatggctac ggcggctggg ggcacgaccc agattgatgt gaaagcctac 14160aatgtgactg cccaaaattt tagtttggcg tttattacga atgatggttc gaagccgaat 14220ggtgtgcctg cggtggctaa ttggattgct gtcggcgtgt gactgtacag gtgttgtggc 14280ggatggtgtg atgttggggg gctgtggtgt cgtggtttac tcctgcactg gtggcctcta 14340tttgtaccgc gttggccacg gttttgggtt ctgttcaggc tgtcacgtct aaatctagga 14400ggcgtttgcg ccgcctgtcg gcgcaggtgg atgcgatgga agagtatacg tggggtgtgc 14460ggcgcgaggt gcgaaggttt aacgccgggc ttcctgacga ggtggagcct atgcatctcc 14520ctgatttgcc cgagtttttg aaagatactg ttgatggtgg aggtgagtag ggttgaggga 14580gttggaggag gagaagcggc agcgccgcaa ttttgagaag gcttcactgg tgttgctgtt 14640tttgtcgctt gtgttattgg ctgtggttgc tgcgggtgct ttgcgtttcg gggctgtatc 14700ctctgagcgg gattcggagc aggcgagggc ccagtcgaat ggtacagccg ccaagggttt 14760agccagcagt gtgcggcagg tgtgtgctca gggtggacgg gagtctgtgc ggcttcacca 14820gtctggtttg tgtgtggatg ctcagcgtgt tgagcgtagt gtgcagggtg tgccgggtcc 14880tgccggtgag cgcggcccgc aaggcccggc aggtgtggac ggccgggatg gtgttaatgg 14940ttcggctggg ctggttggcc ctgtgggtcc gcaggggtcc ccgggtttga atggtgtgaa 15000aggtcctgac gggttgcctg gcgctaacgg ttcggatggc

cgtgatggtg tggacggtgt 15060gaacggcaat gatggcgctg atggtcggga tggttcggcc ggtgagcgcg gtgatgtggg 15120cccctcaggt cctgccggcc cgcaaggtgc acagggtgaa cggggtgagc gcggccccgc 15180cggtgcgaat ggcacgaatg gcaaggacgg taaggatggt gccgacggcc gtgatgggcg 15240ttcggttgtg tctgtgtact gtttcggtgg cctgccaggg tgtgaaacca tcacctgtgg 15300ttaccgtgtc atcccgtaaa tagaagaaga gggaagggtg ttactagtgt tgattgtggt 15360ttttggtggt ggtgtgtggt gagatacatt cctgcagcgc atcactctgc cggctctaat 15420aatccggtga acagggttgt gattcatgca acatgcccgg atgtggggtt tccgtccgcc 15480tcacgtaagg ggcgggcggt gtctacagca aactatttcg cttccccatc gtctggtggt 15540tcggcgcatt atgtgtgtga tattggggag acggtgcaat gcttgtcgga gtctacgatt 15600ggttggcatg ccccgccgaa tccgcattct ttgggtatcg agatttgcgc ggatgggggt 15660tcgcatgcct cgttccgtgt gccggggcat gcttacactc gggagcagtg gcttgatccg 15720caggtgtggc ctgccgttga gagggcggcg gtgctgtgta gacgtttgtg tgacaaatat 15780aatgttccga aaaggaaact gtcggctgcc gatttgaagg ctggcaggcg gggtgtgtgt 15840ggccatgtgg atgttacgga tgcgtggcat cagtcggatc atgacgatcc tgggccgtgg 15900tttccgtggg acaaatttat ggccgtcgtc aacggcggca gtggagatag tggggagtta 15960actgtggctg atgtgaaagc cttgcatgat cagattaaac aattgtctgc tcagcttact 16020ggttcggtga ataagctgca ccatgatgtt ggtgtggttc aggttcagaa tggtgatttg 16080ggtaaacgtg ttgatgcctt gtcgtgggtg aagaatcctg tgacggggaa gctgtggcgc 16140actaaggatg ccctgtggag tgtctggtat tacgtgttgg agtgtcgtag ccgtcttgac 16200aggctcgagt ctgctgtcaa cgatttgaaa aagtgatggt ggtttgttgt gggtaaacag 16260ttttggttag gtttgctaga gcgggcggct aagacttttg tgcaaacgtt tgttgctgtg 16320ttgggggtga cggcgggtgt cacgtatacg gcggagtcgt ttcgtggttt gccgtgggag 16380tctgcgttga ttacggctac ggttgctgcg gtcctgtcgg tggctacctc gtttggtagc 16440ccgtcgtttg tggctggtaa gccgaaaacc acgcctgtgg atgcgggttt ggttccgccg 16500gatgatcccg gaatagtgga gcctcacatg gtggatgtgt cggatcctgg catgatcgag 16560cctgcagatg atgtggatct tggtgtaggc tatgtgccga aacatgctgc cgagtcggag 16620gttggcacgg tagagtcgac tgttgcataa gtgaatatag atgtgtgccc cagcggtgct 16680gccacgattg tgtggtggtt gccgctgggg cactattttt gtatattgcg gtgtggctat 16740gattcgttgc tgtcgatggt gtcttcgagc atctggtaca ggtggaggca ggtagagata 16800gtttcgctgg cctggtcgag aacgttccgg ccgataacat ttttgttgtt gtcgcggtgg 16860cggatgatag accacatgat ctcgtcggct gccgcctgca atagttttgc ctggtatgcg 16920attccagcga gccagtctag tgcttcctgg cttgcatagg gtgtctggtc ctcgctgttg 16980cttgtggggt gtcctgcact gtcgcatagc cacaggattt cgctgcactc gtctagcgtg 17040tcctggtcta tagcgagatc gtcgaggctg acattgttga cggtaaggtt cacgttgtcg 17100agggagatgg gtacaccgta ctggttttcg acaccgtcaa caatgttttc caattgctgc 17160atgttggtgg gctgttgttg gacgatacgg tgtatcgctg tgttgagggt ggtgtaggtg 17220atattgtgtg tgttgttcat cgtgttatgc cattccttcg ttatcgtctg gcctgtagta 17280tgtgctgttt gcgtactcgg ttaacgtcat cagtgtttgg tctgcccact gtttcacagt 17340ctgccttgtc actccgagtc gttgggcggc tgtggcgtag gtttggtcat acccgtatac 17400ttccctgaat gctgccaacc gtgccaaatg ttttcgctgt ttggatggct ggcaggcgag 17460ggtgtagtcg tcgatggcta gctgtagatc gatcatggtg gcaatgttgt tgccgtggtg 17520ttgtggcgcg gttggtgggg gtggcattcc tggctccaca ctgggtttcc atgggcctcc 17580gttccagatc cattgggcgg cttggatgat gtctgcggtg gtgtaggttc ggttcactgg 17640tcatcccctg aacaggttgt ctgggttgct ggtgcggatt gtgtcgaatc gtccgacgca 17700gtggcagtag tcgtacatga gtttgataat gtgttggtgg tctcccaaat aggtgtttcc 17760gctgatgctg taggtggctg tgccgtcttt actaatagtg tatttggcgg tgatggtttc 17820ggggttttcg gtgtcggtga tgatggctgt ggtggtggtg cctacggttt ggagcacggt 17880ggtttgggtt ccgtcgtcga tggtggtttt aaccatgagg tgtgttctcc ctttgtgtta 17940gttgctggtt tggttgtcgg ctagatgaat gatgtcgggt aagggtttcg gctggtctaa 18000atgttgtgtg gttttgttgg ctagccgttt ggctaccctg tagcacattt tggtgtagtg 18060tttgttgtct aggttgtggt attgttcccg caccgcaata tatagcaggg agtcttggta 18120caggtcgtct gcattgattg cggggtagtg tgcggctgtt ttagtgcatg cccggttgag 18180tgtgcgtaga tgatggtctg tggcccacac ccacgatgcg gtggtggcta ggtcggcttt 18240tgttggtcgt cggctcatgg catctctttc atctggctat ctggtagttg tttggtgttt 18300tgttgttgat agtgtagcac acgagtccgg ggtttccggt ggtgcccgtc ttgtgccggt 18360accatgtgga ttcgccttcc atggatgggc attggatgaa ggtgcgttgt ccttgttcgg 18420agatttctag gtggtgcctg tgtccggcca tgaggatgtg ggatgtggtg ccgttgtgga 18480attcttgtcc gcgccaccaa tcatagtgtt tgccggtgcg ccattggtgg ccgtgggcgt 18540gtagtatccg tgtgccggct acttcgacgg tggtggtcat ttcgtctcgg ctggggaaat 18600aaaagtgtag gttggggtat tggttggtga gctggtaggc ttctgcgatg gcgcggcagc 18660agtctacgtc gaaggagtcg tcgtaggtgg tgactccttt gccgaagcgt acggcttctc 18720cgtggttgcc ggggatggat gtgatggtca cgtttttgca gtggtcgaac atgtggatga 18780gttgcatcat ggccatgcgg gtgagcctga tttgttccgt caagggggtt tgtgtgcgcc 18840aggcgttgtt gcctccttgt gacacgtatc cttcgatcat gtcgccgagg aatgcgatgt 18900ggactcgttc gggtttgcct gcctgctgcc agtagtgttt agctgatgtg agggagcgca 18960ggtagtcgtc ggcgaagtgt gatgtttccc cgccggggat gcctttgccg atttggaagt 19020cgcctgcccc gatgacgaag gccgcagtgc tgtagtcggt gcgggtgtcc tgttcgggtt 19080ttgggggtgt ccattcggct agtttatcga cgagttcgtc tacagggtag gggtttgttg 19140cgggttggtg gtcgatgatt ttttgtacgg atctgcctgt ttctccgttg gggagtgtcc 19200attcggagat gcgtgtgcgg cgtacggtgc cgtttgcgag atcatcgcag atggtgtctg 19260cttcgctatc gtggttggct agctgggtga gtagccggtc tatgttgtct atcactgggt 19320atcctcttct tgcggggtgg tgttggcttg tttgcggcgg tagtctttta taacggtggc 19380ggagatgggg tatcctgcct gggtgagctg ttttgctagc catgaggcgg ggatggtttt 19440gtcggcgagc acgtcggcag ccttgttgcc gtagcgttgg atgagtgttt cagttttggt 19500tgccatggtg tcctatcggt tgtgtggtgg gctgccatcc tgtgcggcag tcgccgtcgt 19560ggcctggttt gcgtgtgcac cacgatacgg ttctgtctgt gtggttgagt gttttgccgc 19620acatgacgtt ttgtagatgc tctggcagtg cgccgtcacc ctggttgctg gtttgtgtgt 19680cgaagagtgt tttctggttg gtgaaatgct cggacacggt gccattatgt acgggtagta 19740tccatgtttt ccattgttgt tgtagccggg tgttccagtg gaattgtttt gctgcgttcg 19800tggcttgttt gatggttttg tagtagccga cgaggatgcg ctggtgttca ctgtcgggag 19860ggttttggcc tcgccagtat tgtgccgcca cggcgtagcg gttgctggct gtgaaggcgt 19920cccagcagta ttcaataatg tgttgtagta cactatcggg catgtctcgt acttggtttt 19980cgtcgagcca cgcgtcgaca atgatgttgc gtatggcgcg tttgtctttg gtggtgggtt 20040tgaatgcgat gctcacagta cgggcctgtc gtcttgcatg aaatcattaa aggatgattc 20100gcttgcgcgg cgtgcttgtg tgatttgctg gtcagaccag tcggggtgtt gctgtttcag 20160atagtaccag tggcacgcat tgtaggtttc gtcttgtagc cgggtgagat ggttttcggt 20220gatgatttgt ttccacatag tccatgacac gtcgagccgg tccaatattt ccattgctgg 20280aatgttgaac tggttcagga agagtatttc gtgggtgtag tattccttct cgtactggtc 20340ccatccactt cggtgcctgt tgggctggtt tttggggtag gcttcccggc atactttgtg 20400caaatgtttg gccatgtcgt cgggtagttt aatgtcaggg ttggcgcgga tcatggatcg 20460catcccatca taggtggtgc cccaggtgtg catgatgtag gtggggtctt caccatcagc 20520ccatttttct gcacagatgg cgaggcggat gcgtctcctg gctgattggc tggtgttgcg 20580ccggttgggg atggggcacg tgtcgagggg atccatgatg ttttggtgta cctttcttgg 20640tttaggttgc ttgtgtggtt ttattgtagc actgtgtcta gtgcttgtgt caaccctgtt 20700ttgccggcct gaaggtaggt gtctgtgaca tcccccaggg tgaggggcac atgggtggct 20760tgggggagtg cggcctggag tgtttgggcc atctggtggc ccgccttgtc tgggtctgac 20820cagatgtaga tgtggtcgta gccttcaaaa aatttggtcc aaaaagtttg ccacgaggtt 20880gcgccgggta gggctacggc tggccatccg cattgttcga ggatcatgga gtcgaattcg 20940ccttcgcaaa tgtgcatttc ggctgccggg ttggccatgg cggccatgtt gtagatggag 21000cctgtgtctc ctgccggggt tagatatttg gggtggttgt gggttttgca atcatgttgg 21060agtgagcagc ggaaacgcat ttttcgtatt tcggctggcc cttcccagac ggggtacatg 21120tatgggatgg tgatgcactg gttgtagttt tcgtggcctt ggatggggtc attgtcgatg 21180tatccaaggt ggtggtagcg ggctgtttct tcgctgatgc ctcttgccga gagcaggtcg 21240agtatgtttt cgaggtgggt ttcgtagcgg gctgaggctt tctggattcg gcggcgttcc 21300gcaatgttgt aggggcgtat gctgtcgtac attcgggttt tcttcctcta atcgttgttt 21360cagtttgtgg agtccgcctc cgataccgca tgtgtggcag taccagacgc ccttgtcgag 21420gttgatgctc atggagggct ggtggtcgtc gtggaacggg cagaggatgt gttgctcgtt 21480ccgtgacggg ttgtagcgta tctggtgggc gtctaggagg cggcaggtgt cagaggtgtg 21540ggaggagctc gttgagggtt gataccacat aggcttcgct ccagggtttg ttgcgctgtt 21600tcatgatgac gagtccgatg gtggattggt tttcgcggtt tcggtgtgtt tcgtagttgc 21660gtgcctcccg gctggcttgt ttcacgaatt cggctaggtg tgcctgtcct gctttggctt 21720cgatcacata ggttttgttg ccggttgtga ggatgaggtc gccttcgtct tctttaccgt 21780tgaggtggag gcgttctata tcatagccgg tgtcgcgtag ctggtggagg agtcttgttt 21840cccattcggc gccggctcgg cggttgcgtg cctgttgtgt tgacatgata gtcctttatg 21900ttcttgtgtc atgttccagg gctgtttttc tactaggggc ccgaagaatg tgtattcggg 21960gtaggctcgt agtcgttcgt attttgttcc gtctgggctg gatttgccgg ttctctgttt 22020caggacggcg atgcgtgcct cggcggggat ggtgaggccg ttgccgttgt cttcgccacc 22080atacagggag actcccaata tgagttgtgg tttttcggag aggccgtttt tgatttcccg 22140cctagctggg gggtgttcga tgtcggtgcc ggttttgtcg gttgcgtggt gggtgacgat 22200gatggtggag ccagtatctc tacctaaggc tgtgatccat tgcatggctt cttgctgtgc 22260ctgatagtcg gattcgcagt cttggatgtc catcaggttg tctataacaa taatgggtgg 22320gaaggtgttc cacatttcca tgtaggcttg cagttccatg gtgatgtctg tccatgtgat 22380gggtgactgg aatgagaagg tgatgtgtcc gccgtggtgg atgctgtctc gatagtattc 22440tggcccgtag ttgtcgatgt tgtgttgtat ctgttgggtg gtgtgttggg tgttgagtga 22500gatgattcgt gtggaggcct cccagggtgt catgtcccct gatatgtaga gggctggctg 22560gttgagcatc gcggtgatga acatggctag ccctgatttt tggctgccgg accgccccgc 22620gatcatgacc aaatcccctt tgtggatgtg catgtccagg ttgtcataca agggtgctag 22680ttggggtatg cggggcagtt cggcggctgt ttgggaggcc ctctcgaagg atctttggag 22740agagagcatc gggaccttaa tctatctgtt ggttgggtgt gttttggtgg tcagatggag 22800tcgatgtcga tgtcagcatc ggcgggggct gtggtgtcgt ctagctggcc gttgtcgcgt 22860ttgtctacat attcggcaac cttatcgtag atggcgtcgt cgaggggttt gaggacgacc 22920gcgttgaacc cgtttttggt gcgcacggtg gcaagtttga aggcttgttc ttcgccgaga 22980tatgcttcta ggtcgcggat catggagtgt gggcggtcgt tgttgccgcg tgctttttcg 23040atgatggcgt tggggatggt ttctggggtg ccgttgttga gatcctggag ggtgtggaag 23100attgtgacat cagcgtagat gcggtctgcg acctgtccac cgtagccttc ggtgttgtgt 23160tctacgtcgc ggattttgaa ggcgatggcg gtggcgtcct ggtttcggga ggggttgaag 23220aaggtgctgt tgctgttgtt gtggtagttg gcgagtgcca tgattgtgtt atcctttact 23280gttgtgtctg tttttgttgt cttatattgg tttatcgggt gaggctgttt cgtttgctgc 23340ggaaagcctc ggaaacgtca ctgttactgg tgatggtctt cttgtactgt ttgagtaggt 23400ctgctagctg tgtcttgctg gtggctttgt ttatccggtc gatgatgatg tcgttttcct 23460gtgatgcgat tttgttgacg tagtctttgg cggctttatc gtatcggtct tgaagcagga 23520ttgctgcgct agcgatgagg gttgcgagat cccagtcttt ggatacggtt tcgtctttca 23580atcctcctag cagatcaata atggattgtt tgatgtcttc tgcggtgtct ccgcggatga 23640ctgtccatgg ggcggcatag tcgccaccgt atttgagtgt gatagttagt tttccgctgt 23700ctgtggtgtg ctcgtcggtc acgtgttttc cttttcgttg ttttcggctt ctggtggctg 23760tacggtggtt tctatcgggt atctgtaggc gtctttcccg ttgacggccc agcaggcgtc 23820cttgacgggg catcctttgc agagtgtggt gacgtggggt acgaagatgc cttggctgat 23880tcctttcatt gcttgactgt acatggatga tacatgccgg taggtgttgt tgtcaagatc 23940aatgagttcg gttgctgtgc cctgctcgac tgattgctcg tctcccttgg tggtggcggg 24000tgtccaaaac atgcctttcg tcacatggat gccgtgttgg gcgagcatgt accggtatgt 24060gtgcagctgc atactgtctg cgggtaggcg tccggttttg aggtccaaaa tgaaggtttc 24120gccggtgtcg gtgtcggtga atacccggtc aatatatccg actatttttg tgtcatcgtc 24180gagggtggtt tctaccgggt attcgatgcc tggctggccg tcaataacag cggtggcgta 24240ttctgggtgg ttgcgcctcc atgttttcca gcggtccaca aaggtggggc cgtacatcat 24300ccaccaattg tagtctttct tgtgtggccc gcctgactcg cacatgtttt tgcatattct 24360gccggagggc tttatgtttg tgccttcgga ttcggcgagg gcgatttggg tgtcgaaaat 24420gtttgtgaag gatgagagtt tgtctggcag tgcagggtat tcggcggggt tgtacaggtg 24480taggtcgtat tgttcggtga tgtggtgtat ggcgcttccg gcgatggtgg cgtaccaggt 24540gtggtgttgg gcgtggtagc cgtgtgctag gcgccatttt tcgccgcatt cggcccactg 24600tgtgagtgaa ctgtaggaga tgtggcctgg atggttgatg gttttcgggt attgtgctag 24660gggcattact tgtcgccttt gtgggtgttc catgggttgc gggtgtcttt gccggcgtgg 24720tgttgctggt aggcgaggag tgcgaggcag tgccaggcag cgtgtgccag atgcggcaaa 24780tgtgattcgt tgtcgaggtt gttgccttgc tgccatgata acaggtgccg gtagagggcg 24840tcgacactgt ggctccacgg gtatcctccg gtccagttgt tgtcgccgta cttggtggca 24900ccgtagcctg ccacggagcc tagggcgtgc aaggctgcgg ggtcgatgag ggagagcctg 24960cagagtttca attcttttcg ggcaccgctg ttggggtcgg tgtacatgct ggtgggctca 25020tccatggtgt gtgtgctcct taagcgtggg ttactggtta ttgtcgtggg cgagtgctac 25080ggcgagaata atgatggcga gggtttcagc gatcagtatg ggtgttgtga tcatttagtg 25140tctcggggat tattggtgag tgttgatgca cctaggaggg tggcgagggc gcatgcggcg 25200atggtggcga gggctgcctt gtgtggggtg ccggttgcgt acatccatgt gatgatgccg 25260ccttggatcc aggctagact ggtgaagaac gtttcgtaac tgtgtagctc aatgttgttg 25320ttgggtgtgt tcatgcttgc tcctgaagaa tggtgttgat ggttttataa atgttgtaca 25380ggtcggtttc gatagataac agttggttga tttggtggtc gagatcaatg tctgggttga 25440gggtgtcgat gcgggcggcg atatcggtgg cggtgcgtag gcttactgct gcaccgtgga 25500tgatgtggca catgtcggtg aggccgactt tggcgatata gtgtgacatg agaggcataa 25560taggtgtgct gtctttctgg tcagcgtgaa gggttgatgg acatatcctc tacctgtggt 25620ttgtcttcgg tgccggagac ttggcagaag actttcacat gcgtcttgga tgctccggcc 25680tgtttggcgg tggcaccgta ggcgatagta aaggtgtctt tgtgggcgcc gatgactttg 25740tgtaggaaga ggtcgatgtc ggggttgccg ttccatttga caccgttttc tgcggctgtc 25800tgggtggctt tctgattgca ggcgtgtgcg gcggtgatca tggtgagacc cttgctggtt 25860tcttcacccc ttgcttgggc ttgccggtgg gctttggcct gctcggcttg tagggagcgg 25920actgctgcgg cctggcgggc cttcttctca gccttgcgct gctggacggt tttgggtgtc 25980cattcggtgt tggctgtggt tacctgtggt gcgggttgtg aggcgagtgg cggattgtcg 26040tctggggctg gcatgaagga tgctgcggca ataatggcga ctgtggcgcc tgcgatggtg 26100tagcctgttt tcttgttcat gattttatgt tcccctttcc ggggtgttgt tcgttgctga 26160catggttaat actttcagcg gctgggccca ctgtcaaggc tgcgctcagt ttgtgtgagc 26220gtttcttgtg tggctagggg tgatggcttc tttcgcccaa taggatgtgc caccgctggt 26280ccagtatccg agtttgttgc gctgcatgcc cttggcgtcc atctcgtcga tagtgaggca 26340cctgcggcga ttggggcctg tcttgacccc gtggtcgcct gtccggtgca tgtcgcctga 26400ggtggtactc gtgaatgttt catggcagat ggtacagtgc tctggtcgat atccggtgat 26460tgtgctatcg cacttgtggc atgtccattc catgattgct cctattttcc attataagac 26520ttcctgtagt gccattttag cgccttgcgg gtcttggggg tacaactata taggtcaggt 26580gtttctaggc gattctaggc tcattgtgtg tggctggggt tttatcgggc acacagggtg 26640agcaggtggc caacattgat gcgggtcaca ttccagtaga gttgcgtggc ttccccactg 26700gtgagcggct tccactcgtc atggctgaac acggtgccat cggatgcgat gaacgtgttg 26760gggcgtagct tgtggagttc ggcttccacg ctctgccggt aggcttcggc gaggccctca 26820aaatccatgt ggtcgcaggg gaggttttcg aggcgtgtca ggtcgaaggg tgtggggcag 26880tcgtagctgg cgggggtgta gagctgggtg aagtggttgg cgatcttctg catcatgatt 26940ccttttctga tgatggtgtg ttgagggttt atcgggtgga tgcgacaagg atggcgtcta 27000catcgatcat gtcgatgaga tcgtggagtt cctcggcctc gttctcagtg agtggctgcc 27060aggcgtagtc gccgtatacg gcgccgtcga gggtgacagt ccacgggggc cggatgagtc 27120gtatggcttc ttgtacttta gcgtggtaca tgcggcgcac catatccaga tcgatgtcgt 27180ctgaatggtt tccggtgagg ctgtggaggc tgagcgggtc gatgtctgtc tgcctgtaga 27240gggatgtgaa ggatggggtg atgagtgtgc catccatgag tgtgctcctt tcggtggttg 27300taggggttgt tgtggtttct agagtgtgcg ggctgcgacc ccacagtcaa ggtgtcgctc 27360aaactcagtg agcgtttcat atgggtgtgt tgggtgtgac agatgtcact taagccttga 27420tggcctctct cagcgcctca aatcttctag gggtaggatt atgaagggtt ggccctgctg 27480atcgattcta ggccccatac agggcgtctg aggggtgtgt ctgagtgata gtgggtgtgg 27540cagatgatct agcgagtcaa ggtgccgagc tgagacataa gatctatcat ctaggtgtgt 27600gagatgtatc acatcctccc ggcttggtgt gcaccctcaa ggccacccag tcgatctgac 27660gtggagggtg tagcccagaa atactgttta aagccttcac acggcgccta ggagcgcctt 27720acagggtggg ggctaggtat ttataccccc agcacattct gatcgattct agacgcctac 27780aggagcccga tacacgatca gccatccaga cgcagatcat cagcacctat catggttagc 27840taagcctcaa ctatgtggac agtgttggtt actgtggggg aagaaggaca cggtaaaaga 27900aagaggggga gtatcagctt taaagcctta aggtcttagc gcttagcacc gatggtctta 27960gcagttagca ccgagccccc tcaagggctc ggcatcagcc cgaacaggca cagccatgaa 28020aggagtacac gccatcaggg aaggctttcg agtacgagga gcctcagcga cgagtactcg 28080aaagcctgag ggaacaccca tcagcactga tgagcctagc gtattcggaa aggacacaag 28140agtgaagtgt gacagctgtc cgggagtgaa ccccgttctg actaggggtt tcagccttaa 28200ccaccctcaa aggttacaag actctaagaa aatttaagga aaagtttagg tttaattttt 28260ggacctttac taccaaaaac acccgtttac agccctcaaa cccgcctata gagccaaaac 28320caccagtttg actcatccca ggtggggtat gataggctgg acaggtagcc agctggacgc 28380aaggccggaa agtgctaacg cactttccaa cctcgcttac catcagtcta ccaaacactt 28440aaagacctaa gggcttagcg ctaaggtgct gatagcttag caccgagccc cctcaagggc 28500tcggcatcag tcttaaagcc ttaaatactt aaagtaacta taaaacttta aaagcttaac 28560acttaaggat ataaacttta catcagtgtt taagacttaa aaacttaaaa taactattaa 28620gacttaaagt aactataaaa cattaaagac cttaagtact taaagttaac catcagtctt 28680aaactttact atgataacct ataagtctta aagcttatag gtataataat ataatataag 28740tattaaagct tataagttat aaaagtttta gaagagttaa agggttaact tctttacttc 28800tcttctctct ttggttcttt ctctcttctc ttcttttctt catcggggga gaagaggaac 28860ctttaacgtc aacgctgatg gacttttcgc cgtgtgtctc gtgtgcttct ggtcgcaagc 28920tcccatcgca cactccccac actctttcac ctgtgtccct ttcaggctta gcgtgttcag 28980ctgaaggcgt acagcgtgtc acgcttaaac ccttaacacc aggtaagact taaagtgcat 29040attataagta gaagacttta aaaccttaag ggtgttcctg cttagcctgt gtcctttaac 29100gctaggcgct aagccgtgaa acgtgaacac ccatccaccc ctcttctttt taccgtgtcc 29160ttcttctttt gacaccgctg gggggcgatg tgatcttttt aacatgccag ggggtgcggg 29220tagaaaacaa ccaccccacc acaaacagaa caccccctca aacgcacaaa acagccccca 29280ggatcgatga acagggcaag ggcaaggtat tcataccccc agacgattcc aggccgttag 29340agaggcaaat aagacccgta cagggctagg tgaggaatag acacatcatg gcacgcacca 29400atcgcacagc tagccaagcc caccgacgct ggcggcaacg actcatcacc caagcccaac 29460aacaaggcca aaccgaatgc ccactctgcg gagtcaccat cacctgggac acacacgacc 29520taccaaccag ccccgaagcc gaccacatca cacccgtcag caggggagga ctcaacaccc 29580tcgacaacgg gcaaatcatc tgcagaacat gcaacagaag caaaggcaat cgcagcgaac 29640caaacatcaa attccaacaa caaaccacaa aaacattgat tccatggtga caaacccgcc 29700aacccccacc ggggacaccc cctgcacagg cgtgcaaga 297392863DNABacteriophage PA6 2ggtgtgtggt gagatacatt cctgcagcgc atcactctgc cggctctaat aatccggtga 60acagggttgt gattcatgca acatgcccgg atgtggggtt tccgtccgcc tcacgtaagg 120ggcgggcggt gtctacagca aactatttcg cttccccatc gtctggtggt tcggcgcatt 180atgtgtgtga tattggggag acggtgcaat gcttgtcgga gtctacgatt ggttggcatg 240ccccgccgaa tccgcattct ttgggtatcg agatttgcgc ggatgggggt tcgcatgcct 300cgttccgtgt gccggggcat

gcttacactc gggagcagtg gcttgatccg caggtgtggc 360ctgccgttga gagggcggcg gtgctgtgta gacgtttgtg tgacaaatat aatgttccga 420aaaggaaact gtcggctgcc gatttgaagg ctggcaggcg gggtgtgtgt ggccatgtgg 480atgttacgga tgcgtggcat cagtcggatc atgacgatcc tgggccgtgg tttccgtggg 540acaaatttat ggccgtcgtc aacggcggca gtggagatag tggggagtta actgtggctg 600atgtgaaagc cttgcatgat cagattaaac aattgtctgc tcagcttact ggttcggtga 660ataagctgca ccatgatgtt ggtgtggttc aggttcagaa tggtgatttg ggtaaacgtg 720ttgatgcctt gtcgtgggtg aagaatcctg tgacggggaa gctgtggcgc actaaggatg 780ccctgtggag tgtctggtat tacgtgttgg agtgtcgtag ccgtcttgac aggctcgagt 840ctgctgtcaa cgatttgaaa aag 863329275DNABacteriophage 103609 3cctccctttt gtggattgtc tgtttgtcga ctttttgtgt tggtggtgag tgctgtgcag 60cctgagcttc ctgggtctcg tgagtggtgt ggggagacgc gtcgttggtg gcgtgtgtgg 120ggtgaggata gccgtgcatc gtacgtgtct gatgaggagt ggctgtttct cttggatgct 180gcggtgattc atgattgtgt gtggcgtgag ggtcgcgcgg atttggtggc ttcgcttcgt 240gctcatgtga aggcttttat gggtatgttg gatcggtatt cggttgatgt ggcgtctggt 300ggccgtggtg ggggttctgc ggtggcgatg attgaccggt atcggaagcg taaaggggcc 360taatgtcgag tgtggttggt tctcaggtgc ctcgtcatcg ggtggctgcg gcgtattcgg 420tgtctgctgg cggtgatgct ggggagttgg gtcgtgcgta tgggttgacg cctgatccgt 480ggcagcagca ggtgttggat gattggctgg ctgtcggtag caatggcagg cttgcttcgg 540gtgtgtgtgg ggtgtttgtg cctcgccaga atggcaagaa tgctattttg gagattgtgg 600agttgtttaa ggcgactatt cagggtcgcc gtattttgca tacggctcac gagttgaagt 660cggctcgtaa ggcgtttatg cggttgaggt cgttttttga gaatgagcgg cagtttcctg 720acttgtatcg tatggtgaag tcgattcggg cgacgaatgg tcaggaggct attgtgttgc 780atcatccgga ttgtgccacg tttgagaaga agtgtggctg cagtggttgg ggttcggttg 840agtttgtggc tcgttctcgg ggttctgctc gcgggtttac ggttgatgat ttggtgtgtg 900atgaggctca ggagttgtcg gatgagcagt tggaggcttt gcttcctacg gtgagtgctg 960ccccgtctgg tgatcctcag cagattttcc ttggcacgcc gcctgggccg ttggcggatg 1020gttctgtggt gttgcgtctt cgtgggcagg ctttgtctgg tggtaaaagg tttgcgtgga 1080cggagttttc gattcctgac gagtctgatc cggatgatgt gtcgcggcag tggcggaagt 1140tggcggggga tacgaatccg gcgttggggc gtcgcctgaa ttttgggacc gtaagcgatg 1200agcatgagtc gatgtctgct gccggttttg ctcgggagcg gcttggctgg tgggatcgtg 1260gccagtctgc tacgtctgtg attccggcgg ataagtgggc tcagtctgcg gtggatgagg 1320cgaagctttc tggcgggaaa gtgtttggtg tctcgttttc tcgttcgggg gatcgtgtcg 1380cgttggcggg tgccggccgg actgatgctg gtgttcatgt tgaggttatt gatgggctgt 1440cggggacgat tgttgatggt gtgggccggt tggctgactg gttggcggtt cgttggggtg 1500atactgaccg gatcatggtt gccgggtctg gtgcggtgtt gttgcagaag gcgttgacgg 1560atcgtggtgt tccgggccgt ggcgtggtgg ttgccgatac tggtgtgtat gtggaggctt 1620gtcaggcgtt tcttgagggt gttcgttcgg gtgttgtgtc tcatcctcgt gctgattctc 1680gccgtgacat gttggatatt gctgtgaggt cggctgtgca gaagcgtaag gggtctgcgt 1740ggggttgggg ttcctcgttt aaggatggtt ctgaggttcc tttggaggct gtgtcgctgg 1800cgtatcttgg tgcgaaaaca gttaaagtga agcggcgtga acggtctggt aggaagcggg 1860tgtctgtggt atgaacgtgg acgagttggc tctgattgag ggcatgtacg atcgtatcca 1920aaggttgtct tcgtggcatt gccgtattga gggctactat gagggctcga gccgggtgcg 1980tgatttgggg gtggctattc ctccggagtt gcagcgtgtg cagactgtgg tgtcgtggcc 2040tggtatagct gtggatgctt tggaggagcg tctggattgg cttggctgga ctaatggtga 2100cggctacggc ctggatggtg tgtatgctgc gaatcggctt gctacggctt catgcgacgt 2160ccaccttgat gcactaattt ttgggttgtc gtttgttgcg atcattcctc atggtgatgg 2220tacggtgtcg gttcgtccgc agtcaccaaa gaattgtacg ggcaagtttt cggctgacgg 2280gtctcgtttg gatgcgggtt tggtggttca gcagacgtgt gatcctgagg tggttgaggc 2340tgagcttttg cttcctgatg tgattgttca ggtggagcgg cggggttcgc gtgaatgggt 2400tgaggtggat cgtataccga atgtgttggg tgctgttccg cttgtgccta ttgtgaatcg 2460tcgccgtacg tctaggattg atggccgttc ggagattacg aggtctatta gggcttacac 2520ggatgaggct gttcgcacac tgttggggca gtctgtgaat cgtgattttt atgcgtatcc 2580tcagcgttgg gtgactggtg tgagcgcgga tgagttttca cagcctggct gggtcctgtc 2640gatggcttct gtgtgggctg tggataagga tgatgatggt gacactccga atgtggggtc 2700gtttcctgtc aattcgccta caccgtattc ggatcagatg agactgttag cgcagttaac 2760tgcgggtgag gcggctgttc cggaacgcta tttcgggttt atcacgtcta acccacctag 2820tggggaggct ttggctgccg aggaatctcg gcttgtgaag cgtgctgagc ggcgtcaaac 2880gtcgtttggt cagggctggc tgtcggttgg ttttttggct gccaaggcgt tggattctcg 2940tgttgatgag gccgattttt ttggtgatgt tggtttgcgt tggcgtgatg cttcgacgcc 3000tacccgggcg gctacggctg atgctgtgac gaagcttgtt ggtgccggta ttcttccggc 3060ggattctcgg atggtgttgg agatgttggg tttggatgat gtgcaggttg aggctgtgat 3120gcgtcatcgt gccgagtctt cggatccgtt ggcggcactg gctggggcta tttctcgtca 3180aactaacgag gtatgatagg cgatggcttc gggtgctgtg tcgaggcttg ttgcgactga 3240gtatcagcgt gaggcggtca ggtttgctgg gaagtatgcg gggtattatt cggagcttgg 3300tcgtttgtgg cattccggga agatgacaga tgtgcagtat gtgcgtttgt gtgtggagtt 3360ggagcgtgcc ggccatgatg gttcggcatc gttggctgcc aggtttgtgt cggattttcg 3420ccggttgaat ggtgtggatc cgggtttgat tgtgtatgac gagtttgatg ctgcggcggc 3480tttggctagg tcgttttcga ctatgaagat tcttgagagt gacccggata gggcgaatga 3540cacgattgat gcgatggctg cgggttttga tcgggctgtt atgaatgctg gccgtgacac 3600ggttgagtgg tctgcgggtg cgcagggtag gtcgtggcgc agggtgactg atggtgatcc 3660gtgtgctttt tgtgccatgt tggctacgag gtcggattat acgactaagg aaagggcact 3720cacttccggt catacgcggc gtcataagcg tggtggtaag cgtccgtttg gttcgaagta 3780tcatgatcat tgtggttgta cggtggttga ggttgttggc ccttgggaac caaatagggc 3840tgatgccgag tatcggagga cgtatgagaa ggcccgtgag tgggttgatg atcatgggtt 3900gcagcagtcg cctggcaata ttttgaaggc tatgcgtact gttggtggca tgagataatt 3960tgatgtggtt tccggttgtg cgccgccggt tattggtgca cagggttgtc tcccgcacgg 4020gggtcaacaa tgttgtgttg ttttccgcaa ggagtgtagg gttaggctat ggccgatcag 4080agtgttgagg aacagaatgt tgacaatgat gctgttgagc ccggaaaggg tggagacatt 4140gttgatgttg tgaaggatgg gcaggctgcc ggcgatgatc atgccggtga tgtttccgtg 4200aagggtgagg cttctgggcc gtctgggact gattggaagg cggaggcccg taagtgggag 4260tctcgtgcta aaagtaattt cgccgagttg gagaagcttc gtacatcgag tgacgattct 4320ggatctacta ttgatgagct tcgccgcaag aatgaggaac tcgaagacag gatcaacggg 4380tttgttcttg agggtgtgaa gcgcgaggtg gcttcagagt atggtttgtc cagtgatgcg 4440atcgctttct tgtcgggtgg cgataaggag tcgcttgccg agtctgcgaa agctttgaag 4500ggtttgattg accatagtag tggtggcgcg ggtgtgcgcc gtcttgcggg gagtgccccc 4560gttgatgatg ttaaacgacg tgagggtgtc gcgtttgtgg atgctcttgt caataattct 4620aggagatgat ttctgatggc tgacgatttt ctttctgcag gtaagcttga gcttcctggt 4680tctatgattg gtgcggttcg tgaccgtgct atcgattctg gtgttttggc gaagctttcg 4740ccggagcagc cgactatttt cggcccggtg aagggtgccg tgtttagtgg tgttcctcgc 4800gccaagattg ttggcgaggg cgaggttaag ccttccgcgt ctgttgatgt ttcggcgttt 4860actgcgcagc ctatcaaggt tgtgactcag cagcgtgtct cggacgagtt tatgtgggct 4920gatgctgatt accgtctggg tgttttgcag gatctgattt ccccggctct tggtgcttcg 4980attggtcgcg ccgtggatct gattgctttc cacggtattg atcctgccac tgggaagcct 5040gccgcggctg tcaaggtgtc gctggataag acgaagaaga cggttgatgc caccgattcc 5100gctacggctg atctggtcaa ggctgtcggc cttatcgctg gggctggttt gcaggttcct 5160aacggtgttg ctttggatcc ggcgttctcg tttgctctgt ctactgaggt gtatccgaag 5220gggtctccgc ttgccggtca gccgatgtat cctgccgccg ggtttgctgg tttggataat 5280tggcgtgggc tgaatgttgg tgcttcttcg actgtttcgg gtgccccgga gatgtcgcct 5340gcctctggtg ttaaggctat tgttggtgat ttctctcgtg ttcattgggg gttccagcgt 5400aacttcccga tcgagctgat cgagtatggt gacccggatc agactggccg tgacttgaag 5460ggccataatg aggttatggt tcgtgccgag gctgtgctgt atgtggctat cgagtcgctt 5520gattcgtttg ctgttgtgaa ggagaaggct gccccgaagc ctaatcctcc ggccgagaac 5580tgatttattg ttgcggtgat gtgtcaatgt gcagggggtg gtgttgatgg gtatcatttt 5640gaagcctgag gatattgagc ctttcgccga tattcctaga gagaagcttg aggcgatgat 5700tgccgatgtg gaggctgtgg ctgtcagtgt cgccccctgt atcgctaaac cggatttcaa 5760atacaaggat gccgctaagg ctattctgcg cagggctttg ttgcgctgga atgatactgg 5820cgtttcgggt caggtgcagt atgagtctgc gggtcctttc gctcagacta cacggtctag 5880tactcccacg aatttgttgt ggccttctga gattgccgcg ttgaagaagc tgtgtgaggg 5940tgatggtggg gctggtaaag cgttcactat tacaccgacc atgaggagta gtgtgaatca 6000ttctgaggtg tgttccacgg tgtggggtga gggttgctcg tgcgggtcga atattgacgg 6060ctacgctggc cctttgtggg agatatgata tgaccagttt tccttatggt gaaacggttg 6120tgatgcttca accgactgtt cgtgtcgatg atcttggtga caaggttgag gattgggagc 6180atcctgtaga aaccgtgtac cataacgtgg ccatctatgc ttccgtttcg caggaggatg 6240aggccgcggg gcgtgactct gactatgagc attggtcgat gctgttcaag cagcctgttg 6300tgggcgctga ttatcgttgc aggtggcgta tccggggtgt tgtgtgggag gctgacgggt 6360ctcctatggt gtggcatcat ccgatgtctg gctgggatgc tggtacgcag gttaatgtga 6420agcgtaagaa gggctgatgg gtagtggctc aggatgtgaa tgtgaagctg aacttgccgg 6480gtattcgtga ggtgttgaag tcttctgggg tgcaggctat gttggctgag cgtggcgagc 6540gtgtcaagcg tgcggcctcg gcgaatgtgg gcggtaacgc tttcgataag gcccaatacc 6600gtaatggttt gtcgtcggag gtgcaggttc accgtgttga ggctgtcgct cgtataggca 6660ccacatataa gggtgggaag cgtattgagg cgaagcatgg cacgttggct cgttcgattg 6720gggctgcgtc gtgatcgtct acgatgaccc caggaagtgg gctaaacgcg tgctcaagga 6780tgatggctgg ctgtctggga taccgtgtac ggggacggtg cctgaccggt ttgagggtga 6840ccttatttgg ttggctcttg atggtggccc gcagttgcat gttcgtgagc gagtgttttt 6900gcgggtgaat gtgttttctg atacgccgga tcgtgctatg tcgttggcgc gtcgtgttga 6960ggctgttctg gctgacgggg tggacggtga ccctgtggtg tactgtaaac ggtctactgg 7020tcctgatttg ctggttgatg gtgcacgttt tgatgtgtat tcgctgttcg agctgatatg 7080taggccggca gagtctgaat aagcttattg tttttgtttt aatgtaattg tttgatattt 7140aatgggggtt gtgatggctg caacacgtaa agcgtctaat gttcgctctg ctgttactgg 7200tgacgtgtat attggtgacg cgcacgccgg tgacactatt gatggtgtga agacggttcc 7260ttctgggctt accgcgttag ggtatctgtc ggatgacggg tttaagatta agcctgagcg 7320taaaacggat gatttgaagg cttggcagaa tgcggatgtt gttcgcacgg tggctacaga 7380gtcgtctatc gagatttctt tccagctgat cgaatccaag aaagaagtta ttgaactgtt 7440ttggcagtcg aaggttactg ccggatccga ttcgggttcg ttcgatattt ctcctggtgc 7500caccactggc gtgcacgctt tactgatgga tattgtggat ggcgatcagg ttattcgcta 7560ctatttcccc gaggttgagc tcattgatcg tgacgagatc aagggtaaga atggcgaggt 7620gtatgggtat ggtgtgacgt tgaaggcgta tcctgcccag attaataaga agggtgatgc 7680ggtgtctggt cgggggtgga tgacggcttt aaaagctgat actcctccga ctcctcctcc 7740ggccccggtt cctccgaagc ctgagcctga tccgaatccg ccgtctaata actgatacac 7800atagtttgag ggattgttga tagatgagtg acacaggtta cacgttgaag attggtgacc 7860gtagctgggt gttggcggat gcggaggaga cggctcaggc tgttcctgcc cgtgtgtttc 7920gtcgtgcagc taagattgcc cagtcggggg agtctgcgga tttcgcccag gttgaggtga 7980tgttttctat gctagaagcg gccgccccgg ctgatgcggt ggaggccctg gaggggcttc 8040ctatggttcg tgttgccgag attttccgtc agtggatgga atacaagcct gacggtaagg 8100gtgcctcgct gggggaatag tttggctcca cggcctgatt gatgattatc gtggggccat 8160cgaatacgat ttccgcacca agtttggtgt ttctgtttat agtgttggtg gcccgcagat 8220gtgttggggt gaggctgtcc ggctggctgg cgtgttgtgt accgatacgt ctagccagtt 8280ggcggcccac ctgaatggtt ggcagcgccc gtttgagtgg tgcgagtggg ctgtgctgga 8340catgctggat cattacaggt ctgctaatag tgaggggcag ccggagcctg tggcgaggcc 8400tacggatgag cgtagggccc ggtttacgtc ggggcaggtg gacgatattt tggcgcgtgt 8460tcgtgctggt ggcggggtgt ctcgcgagat taatattatg gggtgaatag tgtatgtctg 8520gtgagattgc ttccgcatat gtgtcgttgt atacgaagat gcctggtttg aaggctgatg 8580ttggtaaaca gttgtcgggt gttatgcctg ctgagggtca gcgttcgggt agtctttttg 8640ctaagggcat gaagttggcg cttggtggcg cggcgatggt gggtgctatc aatgttgcta 8700agaagggcct caagtcgatt tatgatgtga ctattggtgg cggtattgct agggcgatgg 8760ctattgatga ggctcaggct aagttgactg gtttgggtca cacgtcgtct gatacgtctt 8820cgattatgaa ttcggctatt gaggctgtta ctggtacgtc gtatgcgttg ggggatgcgg 8880cgtctacggc tgcggcgttg tctgcttcgg gtgtgaagtc tggcgggcag atgacggatg 8940tgttgaagac tgtcgcggat gtgtcttata tttcgggtaa gtcgtttcag gatacgggcg 9000ctatttttac gtctgtgatg gcccgcggta agttgcaggg cgatgacatg ttgcagctta 9060cgatggcggg tgttcctgta ctgtctttgc ttgccaggca gacgggtaaa acgtcggctg 9120aggtgtcgca gatggtgtcg aaggggcaga ttgattttgc cacgtttgcg gctgcgatga 9180agcttggcat gggtggtgct gcgcaggcgt ctggtaagac gtttgagggc gctatgaaga 9240atgttaaggg cgccctgggt tatcttggtg ctacggctat ggcgccgttt cttaacgggt 9300tgcggcagat ttttgttgcg ttgaatccgg ttatcaagtc tatcacggat tctgtgaagc 9360cgatgtttgc tgccgtcgat gctggtattc agcgtatgat gccgtctatt ttggcgtgga 9420ttaatcgtat gccgggcatg atcacgagaa tgaatgcaca gatgcgcgcc aaggtggagc 9480agttgaaggg catttttgcg agaatgcatt tgcctgtccc taaagtgaat ttgggtgcca 9540tgtttgctgg cggcaccgca gtgttcggta ttgtggctgc cggtgtgggg aagcttgtcg 9600cggggtttgc cccgttggcg gtgtcgttga agaatctgtt gccgtcgttt ggtgctttga 9660ggggtgccgc cggcgggctt ggcggcgtgt ttcgcgccct gggtggcccc gtcgggattg 9720tgatcggctt gtttgctgcc atgtttgcca ctaacgccca gttccgtgcc gctgttatgc 9780agcttgtcgg ggttgttggc caggctttgg gccagattat ggccgctgtg cagccgctgt 9840ttggtttggt ggctggtttg gtggcacggt tggctcccgt ttttggccag attattggtt 9900tggttgccgg tttggctgcg cagcttgtgc ctgtgattag tatgctggtt gctcggctgg 9960ttcctgtgat cacgcagatt attggtgcgg tgacacaggt tgccgcaatg ttgttgccgg 10020tgttgatgcc ggtgttgcag gctgttgttg ctgtgatacg gcaggttgtt ggcgtgatca 10080tgcagttggt gcctgttttg atgcctgtga ttcaacagat tttgggtgcg gtcatgtctg 10140ttctgccgcc tatcatcggt ctgatccggt cgttgatacc agtcatcatg tcgattatgc 10200gtgtggtggt gcaggttgtt tcggttgtgc tgcaggtggt ggcccgcatt attccggttg 10260tgatgccgat tgtgacagct gtgatcgggt ttgttgcccg tattgttggt gctgtcgtgt 10320cggctgttgc ccgtgttatt gctgctgttg cccgtgttat cgggtgggtt gtggcccatt 10380ttgtgtctgg tttggcgcgt atgggttcgg ttattcaggc tggctggaat catattagag 10440cgtttacgtc tgcgtttatt aacggtttca agtcggttat ttctgccggt gttgccgcgg 10500ttgtggggtt ttttgcccgg cttggttctt cggttgcttc tcatgtgagg tctggtttta 10560acgcggctcg tggtgctgtt tcttctgcga tgaatgctat ccggagtgtt gtgtcttcgg 10620tggcgtctgc tgttggcggg tttttcagtt cgatggcgtc tagggttcgt agtggtgctg 10680tgcgcggttt taatggtgcc cggagtgcgg cttcttctgc tatgcatgct atggggtccg 10740ctgtgtctag tggtgtgcat ggtgtgctgg gttttttccg gaatttgcct ggcaatattc 10800ggcgtgcgct tggtaatatg gggtccttgt tggtgtctgc tggccgtgat gtggtgtctg 10860gtttgggtaa tggtatccgg aatgctatga gtggcttgtt ggatactgtg cgtaatatgg 10920gttctcaggt tgctaatgcg gcgaagtcgg tgttgggtat tcattccccg tctcgggtgt 10980ttcgtgacca ggttggtcgc caggttgttg ccggtttggc tgagggtatt actgggaatg 11040ctggtttggc gttggatgcg atgtcgggtg tggctggtcg gcttccggat gctgtggatg 11100cccggtttgg tgtgcgatcg tctgtgggct cgtttacccc gtatggcagg tatcagcgtg 11160ctaagggtga gagtgttgtg gtgaatgtga atggacctac gtatggtgat cctaacgagt 11220ttgcgaagcg gattgagcgg cagcagcgtg acgctttgaa cgcgttggct tacgtgtgat 11280tgggggtgtt gttcatgttt cttcctgacc cgtctgatcg ttctggtttg actgtgacgt 11340ggtttatgga tccgctgttt ggtggggagc gtgtgcttca tttgacggat tatacgggtg 11400cgtctcctgt catgttgttg aatgattcgt tgcgcggttt gggtgttccc gaggtggagc 11460atttttctca aacacatgtt ggggtgcacg gctcggagtg gcgcgggttt aatgtgaagc 11520ctcgcgaggt gacgctaccg gtgttggtgt cgggtgttga cccggatccg gatggcgggt 11580ttcgtgacgg ttttttgaaa gcctatgacg agttgtggtc tgcttttcct cctggcgagg 11640agggggagtt gtcggtgaag accccgtctg gtcgtgagcg tgtgctgcgg tgccggtttg 11700attcggctga tgacacgttt acggtggatc cggtaaatcg tggctatgcg cgctatctgt 11760tgcatttgac agcttatgac ccgttttggt atggggagga gcaaaagttt cgtttcagta 11820acgctaagtt gcaggattgg ctgggtggcg gccctgtcgg caaggatggc acggcttttc 11880ctgtggtgtt gacgcctggt gttggttctg gctgggataa tctgtctaat aagggtgatg 11940tgcctgcgtg gcctgtgatt cgtgttgagg ggcctttgga gtcgtggtct gtgcagattg 12000atggtttgcg tgtgtcttcg gattatcctg tcgaggagtt tgattggatc acgattgata 12060cggatcctcg ccagcagtct gcgttgttga atgggtttga ggatgtgatg gatcgtttga 12120aggagtggga gtttgcgcct atcccgcctg gcggttctaa gagtgtgaat attgagatgg 12180ttggtttggg tgccattgtt gtgtcggtgc agtacaggtt tttgagggct tggtgaatag 12240ttgatggctg gtcttgtccc gcatgtaacg ttgtttacgc cggattatcg ccgtgtggcg 12300cctatcaatt tttatgagtc gttgaagttg tcattgaagt ggaatggttt gtcgacgctg 12360gagttggtgg tgtcggggga tcattccagg cttgacgggt tgactaggcc gggtgcgcgg 12420cttgtggttg attatggtgg tggccagatt ttttctgggc ctgtgcgtaa ggttcatggt 12480gtgggtccgt ggcgttcttc gcgggtgact atcacgtgtg aggatgatat ccggctgttg 12540tggcgtatgt tgatgtggcc tgtgaattat cgtcctggta tggttggtat ggagtggcgt 12600gccgacaggg attatgccca ctattcgggt gcggctgagt cggtggctaa gcaggtgttg 12660ggggataatg cttggcgttt tccgcctggt ttgtttatga ccgatgatga gcgtcgtgga 12720cgctatatta aggattttca ggtgcggttc cacttgtttg cagacaagtt gttgccggtg 12780ttgtcgtggg ctcggatgac tgtcacggtg aaccagtttg agaatgcgca gtttgatcag 12840cggggtttgc tgtttgattg tgtgcctgct gtgacccgga agcatgtgtt gactgccgag 12900tctggttcga ttgtgtcgtg ggagtatgtg agggatgccc ctaaggctac ttcggtggtg 12960gttggtggcc gcggcgaggg taaggatcgg ctgttttgtg aggatgttga ttcgatggcc 13020gagggggatt ggtttgatcg tgtagaggtg tttaaggatg cccgtaacac ggattctgag 13080catgtgcatc tcatcgatga ggctgagcag gtgctgtccg agttaggggc cacgtcgggg 13140tttaagatcg agttggctga gtcggatgtg ttgcggtttg ggccaggcaa tctgatgccg 13200ggtgatctta tctatgtgga tgtgggttct ggccctattg cggagattgt gcggcagatt 13260gatgtggagt gtgattcgcc tggtgatggt tggacgaagg tgactcctgt tgcgggggat 13320tatgaggata atccgtcggc gttgttggct cgccgtgtgg ctggtttggc tgcgggtgtg 13380cgggatttgc aaaagttttg acaagtgatt ggggtttgtt gtgggtattg tgtgtaaagg 13440gtttgatggt gtgttgaccg agtatgattg ggctcaaatg tctggtctga tgggtaatat 13500gccgtccgtg aaagggccgg acgattttcg tgtcggcacg acaattcagg gtgccacagt 13560gttgtgtagt gttttgccgg ggcaggcttg ggctcacgga gtgatgtgca cgtcgaatag 13620tgttgagacg gtgacagggc agctgcctgg cccgggcgag acccgatacg actatgttgt 13680tctgtctcgg gattgggagc agaacacagc caagttggag attgttcccg gtggccgtgc 13740ggagcgtgcc agggatgtgt tgcgtgccga gcctggcgtg tttcatcagc aactgttggc 13800gactttggtg gtgtcgtcta acgggttgca gcagcagctg gataggcgtg ctatagcggc 13860ccgtgtggcg tttggcgagt ctgcggcttg tgatcctacc cctgtggagg gtgaccgggt 13920gatggttcct tcgggggctg tgtgggctaa tcatgctaac gagtggatgt tgttgtctcc 13980gaggattgag acgggttcta agtcgatcat gtttggcggg tctgctgtgt atgcttacac 14040gatcccgttt gagcggccgt ttagtagtgc gcctgttgtg gtggcgtcta tggctacggc 14100ggctgggggc acgcagcaga ttgatgtgaa agcctacaat gtgactgcca aggattttgg 14160tttagcgttt atcacgaatg acgggtctaa accgaatggt gtgcctgcgg tagctaactg 14220gattgctgtc ggcgtgtaat gcgctgcttg tgtgtgcggg atatgttgtg gtggttgtag 14280tggtaggggg ctgtagtgtc atggcttaca cccacactcg tagcctctat ttgtaccgct 14340atcgctactg tccttggttc gattcaggcg gttacttaca ggtcgaagaa gaggcttagg 14400cagttgtctg cacaggttga tgcgatggaa gaatacacat ggaatattcg ccatattgtt

14460catcgctata acgcgaattt gcctgagaat gttgagcctg taaaaatgcc tgatttgccc 14520gagtttttga aggatactgt tgatagtggt ggggggtgaa ttgtgaggga gttggaggaa 14580gagaaacggc agcgccgcaa ttttgagaag gtttcattgg tgttgctgtt tttgtcgctt 14640gtgctactgg tggcgatggc tgggggtgct ttgcggtatg gttctgtggc ttcgcaaagg 14700gattcggagc aggcgagggc ccagtctaat ggtacagccg ctaaagggtt ggccagccgt 14760gtgcggcagg tgtgtgcttc ggatgggcag gagtcggtgc ggcttcatca gtctggtttg 14820tgtgtggatg ctgtgcgtgt tgagcgtagc gtgcagggtg tgccgggccc tgccggtgtg 14880cgcggcccgc aaggaccggc tggtgttgca ggtgttgacg gccgtgacgg tgtgaatggt 14940tcggcgggtg ttgtggggcc tgtgggtccg cagggttctc cgggtttgaa tggtgtggct 15000ggcccggacg ggttgcctgg cgtgaatgga tcggatggcc atgatggtgt tccaggtcgt 15060gcaggtgctg acggtgtgaa cggcgttgac ggtcgggatg gttcggccgg tgagcgcggt 15120gatgtgggcc cttcaggtcc tgccggcccg caaggtgcac agggtgaacg gggtcctatt 15180gggcctcagg gtccgcaggg ttctgccggt gctgacggca cgaatggtaa agacggtaaa 15240gatgggcgct cggttgtgtc tgtgtactgt tccgagggcc gcctggttgt gaaatatagt 15300gacggtgtgg cttctacaat atcgagctcg gtggcctgcc agggtgtgaa accgtcgcct 15360atagtgacta tatcatccca caagtaaaaa agaaaaggga agggtgttac tagtgttgat 15420tgtggtgtta ggtggtgtgt ggtgagatac attcctgcgg cgcatcattc tgccggctcg 15480aatagtccgg tgaatagggt tgtgattcat gcgacgtgcc cggatgtggg gtttccgtct 15540gcctcgcgta aagggcgggc ggtgtctaca gcaaactatt tcgcgtcccc atcgtcgggt 15600ggttcggcgc attatgtttg cgatattagt gagactgtgc agtgcttgtc ggagtctacg 15660attgggtggc atgccccgcc gaatccgcat agtttgggta tcgagatttg cgcggatggg 15720ggttcgcacg cctcgttccg ggtgccgggg catgcttaca ctcgggagca gtggcttgat 15780cctagggtgt ggcctgcggt ggagaaggct gccatcctgt gtagacgttt gtgtgacaaa 15840tataatgttc cgaagaggaa gcttagtgca gccgatttga aggctggtag gcggggtgtg 15900tgcggccatg tggatgtgac ggatgcgtgg catcagtcgg atcatgacga tccggggccg 15960tggtttccgt gggacaggtt tatggccgtt gtcaacggca aagatgagag tggggagtta 16020actgtggctg atgtgaaagc cttgcatgat cagattaaac aattgtctgc tcagcttact 16080ggttcggtga ataagctgca ccatgatgtt ggtgtggttc aggttcagaa tggtgatttg 16140ggtaagcgtg ttgacgcctt gtcgtgggtg aagaatccgg tgacggggaa gctgtggcgc 16200acaaaggatg ctttgtggag tgtctggtat tacgtgctgg agtgtcgtag ccgtattgac 16260aggcttgagt cgactgtcaa cggtttgaaa aagtgatggt ggtttgttgt gggtaaacag 16320ttttggttgg gcttgtttga gcgtgccctg aaaactttta ttcaaacgtt tgttgctgtg 16380cttggtgtga ctgcgggtgt cacgtatacg gcggagtcgt ttcgcggttt gccgtgggag 16440tcggccctga ttacggccgg ggttgctgca atactgtcgg ttgctacctc gtttggtagc 16500ccgtcgtttg tggccggcaa acctaaaacc acggttgtgg atgctggtct tgttccaccg 16560gatgatgggg gcatggttga gccgcactcg gtggatgtgt cggatcctgg catgattgag 16620ccgacagatg atgtggatgg ttttgtcggc tatgtgccga ggcgtgcagc cgagtctgag 16680gttggcacga tagagccgat cgaatgataa gtgaacatag atgtgtgccc cagcggtgct 16740gccacgatcg tgtggtggtt gccgctgggg cactatttct gtttatgcgg tgtggctata 16800attcgttgcg gtcgatggtg tcttcgagca tctgatacag gtggaggcag gtagagatcg 16860tatcgctggc ctggtctaga acgttccggc cgataacgtt tttgtggttg tcgcggtggc 16920ggatgatagc ccacatgatc tcgtcggctg ccgcctgcaa tagttttgcc tggtatgcga 16980ttccggcgag ccagtctagt gcttcctggc ttgcataggg gctctggtcc tcgctgttgt 17040cacgggtgtt gctgttgttt gtggggcgtc ctgcactgtc gcataaccac aggatttcgc 17100tgcactcgtc tagcgtgtcc tggtcgatag cgagatcgtc gaggctgact tcgttgacgg 17160taaggttcac gttgtcgagg gagatgggta caccgtactg gttttcgaca ctgtcaacaa 17220tgttttccag ctgttgcatg ttggtgggct gttgttggac gatacggtgt atcgctgtgt 17280tgagggtggt gtaggtgata ttgtgtgtgt tgttcatggt tttatccaat ccctgtgctt 17340tcgtcgtttt cgtctggata gtatctactg tttgcgtagc ctgttagggt gatcagtgtt 17400tggtctgccc actgtttcac ggtttgtctt gtcactccga gtcgttgggc ggctgtggcg 17460taggtttggt catacccgta tacttccctg aaggctgcga gcctggctag ccgttttcgc 17520tgtttggatg gctggcaggt gagggtgtag tcgtcgatgg ctagctgcaa atcgatcatg 17580gagacgatgt tgttgccgtg gtgttgtggc gcggttggtg gtggtggcat gcctggttcg 17640acactcggtt tccatgggcc tccgttccag atccattggg cggcttggat gatgtcggcg 17700gtggtgtagg ttcggttcac tggtaatcct taaacaagtc gttcatgttg ctggtgttgg 17760tggtgtcgaa tcgtccgacg cagtggcagt agtcgtacat gagtttaata atgtgttggt 17820ggtcgccgag gtaggtgttg ccgctgatac tgtaggtggc tgtgccgtct ttgctgatgg 17880tgtatttggc ggtgatggtt tcgggtgttt cggtgttggt gatgatggct gtggtggtgg 17940cgcctacggt ttgtagtctg gtggtttggg tgccgtcgtc gaggatggtg gtgaccatta 18000tgattctcct tagttgctgg tttggttgtc ggctatggct gtgatttctt gtaccggttt 18060gggtagatct aaatgctgtg tggttttgtt tgctagtcgt tgggctacac ggtagcccat 18120ttgggtccac tggttgcctt ccagctggtg gtattggttg cgtacggcta tgtagaggag 18180tgcgtcttga tagaggtcgt cggggttgat ggccgggtag tggcgcgcaa tgttggtgca 18240ggctttgtgt agctggtgtt ggtggtgtgg ggttgcccat tcccagttgg cggtggtggc 18300ttgttctact ttggttggtc gtctgctcat ggcactatta cctggctatc tggtagttgt 18360tgggtgtttt gttgttgata gtgtagcaca cgagtccggg gtggccggtg gtgcctgtgc 18420ggtgccggta ccagacggat tctccttcca tggatgggca ttggatgaag gtgcgttgtc 18480cttgctctga gatttcgagg tggtgccggt gccctgccat gagaatatta gatacggtgc 18540cgttgtggaa ttcttggccg cgccaccatt cgtagtgttg gttgttgcgc cattggtgtc 18600cgtgggcgtg caggatagta gccccggcta cgtttacggt ggtggtcatt tcgtccctgt 18660cagggaagtg gaagtgtagg ttggggtagt ggttggtgag ttggtaggct tctgcgatgg 18720cgcggcagca gtccacgtcg aaggagtcgt cgtaggtggt gacgcctttg ccgaagcgca 18780cggcttcacc gtggttgccg gggatggatg tgatggtcac atttttgcag tggtcgaaca 18840tgtggacgag ttgcatcatg gccatgcggg tgagcctgat ttgttccgtc aagggtgttt 18900gtgtgcgcca ggcgttgttg ccgccttgtg acacgtatcc ttcgatcatg tcgccgagga 18960atgcgatgtg gactcgttgc ggtttgcctg cttgctgcca gtagtgtttg gcggctgtga 19020gggagcgtaa atagtcgtcg gcgaagtgtg atgtttcccc gccggggatg cctttgccga 19080tttgaaagtc tcccgcccct accacgaacg caacattgct gtagtcggtg tgtgtgtctt 19140ggttgggttt ggggggtgtc cattcggcta gtttatcgac gagttcgtcg accggatagg 19200ggtcggttgc gggttggtgg tcgatgattt tttgtatgga tcggcctgtt tctccgttgg 19260ggagtgtcca ttcggagatg cgtgtgcgcc gtacagtacc attggctaga ttgtcgtcga 19320tggtgtcgat ggcgttgtcg tggttggcta gttgtgtgag gagccggtct atattgtcta 19380tcatcggata tcctcttcct tttgcggggt ggtgttggct tgtttgcggc ggtagtcttt 19440tataacggtg gcggagatgg ggtatcctgc ctgggtgagc tgttttgcta gccatgaggc 19500ggggatggtt ttgtcggcga gcacgtctgc agccttgttg ccgtagcgtt gaataagggt 19560ttcagttttg gttgccatga tgtcccatcg gttgtgtggt gggctgccat cctgtgcggc 19620agtcgccgtc gtgtcctggt ttgcgggtgc accacgatac ggttccgtct gtgtggttga 19680gtgttttgcc gcacatgacg tcacgtaggt gctcgggaaa ctcatcgttg ttgttgtccc 19740cgtgcatgtc gatcaagtgt tgggttttag taaccatcat gcctcctatg tgtgaaagag 19800tgtgcaaata ctatgcaggt gtcatggatg tttatgcggg tatggttttc atcaccttgc 19860tgaacgttac ttggttactg tacatcatct gagtgatttc ctgatcagtc ttatcggggt 19920gctgctttcg caggttcgcc cactggcagg cgttttcggt ctcctgctgt aaacgtgtca 19980ggtgctgctc gttgatgatg tgtttccaca ttgtccatga cacgtcgagc ctgcggagca 20040tgttcatggc tggcacgttg aaggaattga ggaagagtat ttcttcggtg tagtactgtt 20100tttcgtattg gtcccatccg cttcggtgcc tgttgggctg gtttttgggg taggcttccc 20160ggcagatttt gtgtaaccgt ttggccatgt cgtcgggtag tttaatgtcg gggttggcgc 20220ggatcatgga tcgcatcccg tcataggtgg tgccccaggt gtgcatgata tgcagtgggt 20280cttcaccgtc tgcccatttt tctgcacaga tggcgaggcg gatacgcctc ctggctgttt 20340ggctggtgtt gcgccggttg gggatggggc acgtgtcgag gggatccatg atgttttggt 20400gtacctttct ggtttcgtgt tgttgacgtg ttttactgta gcacagtgtc tagtgcttgt 20460gtcaaccctg tttttccggc ctgcaggtag gtgtctgtga catcccccag ggtgaggggc 20520acatgggtgg cttgcggtaa tgcttgggtt agggtttggg ccatctggtc gcctgcgggg 20580tctgggtctg accagatgta gatgtggtcg tagccttcga aaaatttggt ccaaaagttt 20640tgccacgagg ttgcgccggg tatggctacg gctggccatc cgcattgttc gaggatcatg 20700gagtcgaatt cgccttcgca aatgtgcatt tcggctgccg ggttggccat ggcggccatg 20760ttgtagatgg agcctgtgtc tcctgccggg gttaagtatt tggggtggtt gtgggttttg 20820cagtcgtgtg ggagtgagca gcggaaacgc atttttcgta tttcggctgg ccgcccccaa 20880actgggtaca tgtatgggat ggtgatgcac tggttgtagt tttcgtggcc tggtatgggg 20940tcattgttga tgtatccaag gtggtggtag cgggctgttt cttcgctgat gcctcttgcc 21000gagaggaggt cgagtatgtt ttcgaggtgg gtttcgtagc gggctgaggc tttctggatt 21060cggcggcgtt ccgcaatgtt gtatgggcgt atgctgtcgt acattcgggt tttctttctc 21120taattgttgt tgtagcttgg cgagtccgcc tccgataccg catgtgtggc agtaccagac 21180gcccttgtcg aggttgatgc tcatggaggg ctggtggtcg tcgtggaacg gacagaggat 21240gtgttgctcg tttttggatg ggttgtagcg tatctggtgg gtgtcgagga ggcggcgggt 21300gtcagaggtg tgggaggagc tcgttgaggg ttgataccac ataggcttcg ctccagggtt 21360tgttgcgttg tttcatgatg acgagtccga tggtggaatt gttttgtttg tttcggtgtg 21420tttcgtagtt gcgtgcctcc cggctggctt gtttcacgaa ttcggcgagg tgtggctggc 21480cggctttggc ttcgatcaca taggttttgt tgccggttgt gaggataagg tcgccttcgt 21540cttcacggcc gttgaggtgg aggcgttcta tatcatggcc ggtgtcgcgt agttggtgga 21600ggagtcgtgt ttcccattct gcgccggccc tgcggtttct tgattgttgt gtcgacatga 21660tagtcctttg tgtgttgtgg tcatattcca gggctgtttt tcggcgaggg gcccgaagaa 21720ggtgtattcg ggataggctc gtagccgctc gtatcgggtg ccgtcggggc tggatttgcc 21780tgtgcgctgt ttgaggacgg cgatgcgtgc ctctgccggg atcgatagcc cgttgccgtt 21840atcctcgcca ccatacaacg agactccgag gatgagttgt ggtttttcgg agaggccgtt 21900tttgatttct cgccgggcgg gcgggtgttc gatgtcggag ccggttttgt cggttgcgtg 21960gtgtgtgaca ataatggtgg agccagtatc gcggccgagg gctgtgatcc attgcatggc 22020ttcttgctgg gcctgatagt cactctcgca gtcttggatg tccatcaggt tgtcgataac 22080gatgatgggt gggaaggtgt tccacatttc catgtaggct tgcagttcca tggtgatgtc 22140tgtccatgtg atgggtgact ggaatgagaa tgtgatgtgt tggccgtggt ggatgctgtc 22200tcgatagtat tctggcccgt agtcgtcgat gttttgttgt atctgggcgg tggtgtgttg 22260ggtgttgagt gagatgattc gtgtggaggc ctcccagggt gtcatgtccc ctgatatgta 22320gagggctggc tggttgagca tcgctgtgat gaacatggct agccctgatt tttggctgcc 22380ggaccgcccc gcgatcatga cgagatcccc tttgtggatg tgcatatcct ggttgcggta 22440gaggggttct agttgtggta tgcggggcag ctcggctgcg gtttgggagg ccctctcgaa 22500ggatcgttgg agagagagca tcgggacctt atctatctat cggttacgat ttgtatgaat 22560attggcggtt agatggagtc gatgtctaca tcatcactac cagtggtgtt gggctgactg 22620tctcgctggt caacgtaggc tgctacaagg tcgtagatgg cgtcgtccaa tggtttgagc 22680acgaccgcgt tgaagccgtt tttggtgcgc acggtggcga gtttgaaggc ttgctcttcg 22740ccaaggtagg tttcgaggtc gcggatcatg gagtgtgggc ggtcgttgct gccgcgtact 22800ttttcgatga tggcgttggg gatggtttct ggggtgctgt tgttgaggtc gtctagggtg 22860tggaagatgg tgacatcagc gtagatgcga tcggcggtct gtccaccgta gccttcagtg 22920ttgtgctcga cgtcgtggac tttgaaggcg atggcggtgg cgtcctggtt tcgggagggg 22980ttgaagaagg tgctgttgct gttgtttcgg tagtttgcga gtcccattgt tgtttccttt 23040actgttttgt tgatttgtgt cggtttttat cgggtgaggc tgtttcgttt gctgcggaac 23100gcctcggata cgtcagtgtt gctggtgatg atcttcttgt actgtttcag aaggtcggct 23160agctgtgctt tgcttgttgc attgttgatt ttgtcaatga tggtgttgtt tccttcactg 23220gcaatgttgt ctacgtagtc tttggcggcc tggttgtatc ggtcttggag gatgatggat 23280gcggaggcga tcagtgttgc caggtcccag ttccttgccg ccgagctgtt tttgagtccg 23340cctagcaggt cgatgatagt cttctttact tcgtcggcgg tgtctccacg gatgactgtc 23400catggggcgg cgtagtctcc gccgtatttg agtgtgatgg tgatgcgatc atcagtgctg 23460ttggtgttat cgttcactgg tgctccttgc tttcttctgt tggggctgtg atggtggttt 23520ctgtagggta cctgtaggcg tctttcccgt tgacggccca gcaggcgtcc ttgacggggc 23580atcctttgca gagtgctgtg acgtggggta cgaagatgcc ttgactgatt cctttcattg 23640cttgactgta catggatgat acatgctggt aggtgttgtt gtcaaggtcg tacagttcgg 23700tggatgtgcc ttgtgtcggg gacttgtcgt cgttgcggct ggtggctggc gtccaaaaca 23760tgccttttgt cacatcgttg ccgtgttggg cgagcatgta ccggtatgtg tgcagctgca 23820tgctgtctgc tggtaggcgt ccggttttga ggtcgaggat gaaggtttcg ccggtgtcgg 23880tgtcggtgaa aacgcggtcg atgtagccga cgatttgggt gccgtcgggg agggtggttt 23940cgactgggta ttcgatgccg ggctggccgt ctaggactgc tgtgtggtat tgtggattgt 24000ttgtgcgcca gtttttccac cggttgacga aggtttggcc gtagagcatc caccagtcgt 24060agtctttttt gtgtggcccg cccgactcgc acatgttttt gcatattctg ccggagggtt 24120tgatttctgt gccttcggat tcggcgaggg ctacttgggt gtcgaaaatg tttttgaagg 24180atgagagttt gtctggcagt gcagggtatt cggcggggtt gtacaggtgt aggtcgtatt 24240gttcggtgat gtggtgtatg gcgcttccgg cgatggtggc gtaccaggtg tgatatgtgg 24300ctttgtatcc gtgttggagg cgccattttt cgccgcattc ggcccactgt gacagtgatg 24360agtaggagat gtggcctgga tggttgatgg ttttcgggta ttgtgctaga ggcattactt 24420gtcgcttttg ttccatgggt tgcgggtgtc ctggccggcg tggtgttgct gataggcgag 24480gagtgcgagg cagtgccagg cggcgtgtgc caggtggggt agccctgatt catcgtcgag 24540gttgtgtcct tgctgccagg ctagcaggtg cctatagagg gcgtcgacac tgtggctcca 24600cgggtatcct ccggtccagt tgttgtcgcc gtatttggtg gcaccgtagc ctgcaacctc 24660gccgagagcg tgcaaggctg cggggtcgat gagggagagc ctgcagagtt tcaattcttt 24720tttggcaccg ctgttggggt cggtgtacat gcgggttggc ttatccatgg ggtgtgtgct 24780ccttgggggt gggttactgg ttgttgttgt gggctagggc gacggcgaga ataatgatgg 24840cgagggtttc agcgatgagg attggtgttg tgatcatttg ttgtttttgg gctggtaggt 24900gagtgtggag gcacccagga gggtggtgag ggcgcatgcg gcgatgatgg cgagggctgc 24960cttgtgtggg gtgccggttg cgtacatcca tgtgatgatg gcgccttgga tccatgccag 25020tgtggtgaag aacgtttcgt agctgtgtag ctcaatgttg ttgggtgtgt tcatgcttgc 25080tcctggatga tggtgttgat ggttttgtag atgttgtaca ggtcggtttc gatggtttgt 25140agctgtttga tttggtggtc gagatcaatg tttgggttga gggtgttgat gcgggatgcg 25200atgtcggtgg ctgtgcggag tgtgccgccg gtgtggtgaa tgatgtgtgc cgtgtcggcg 25260agtccggtgg tgacagcgta gtgggagagg agaggcatag cggtccttgg cgggttagtg 25320ttgcgggttg atgttgaggt cggtgacgtg gggtgtgttt tctgttccgg tgacgaggca 25380gtggacggtg acgggtagtt tggatgctcc gggctggcgg acggtggcgc cgtagacgat 25440agtaaaggtg tctttgtggg cgcctatgac tttgtggagt tggaggtcga tgtcggggtt 25500gccgttccag ttgacaccgt gtgcggcggc ttgttgttcg gctttgcggt tgcaggtgtg 25560tgcggcggtg atcatggtga gaccttgtga ggtttcttca ccgcgtgttt gggcttgccg 25620gtgggctttc tgctgttcgg ctcgcagtga ctgttctgcg gcggcttgcc gggctttctt 25680ttcggctttg cgctgttgga cggttttggg tgtccattcg gtgttggctg tggtggcctg 25740tggggctggc tgtgaggcga gtggcggatt gtcgccgggg gctggcatga atgaggcggc 25800ggcaatgatg gcggctgtga tgccggcgat ggtgtagcct gttttcttgt tcatgttttg 25860tgtccccttt ccggggtgtt gttcgttgct gacatggtta atactttcag cgactgggcc 25920cactgtcaag gctacgctca acgattgtga gcgattcgtg tgtggctagg ggttttatcg 25980gctgtacagg gtgagtagat ggccaacgtt gatgcgggtc acatgccagt agagttgtgt 26040ggcttcctca ctggtgagtg gcttccactc gttgtggctg aatacggtgc catcagtggc 26100gataaacgtg ttggggcgta gcttgtggag ttcggcttcc acactctgtc ggtaggcttc 26160ggcgaggccc tcaaaatcca tgtggtcgca ggagaggttt tcgaggcgtg tcaggtcgaa 26220gggtgtgggg cagtcgtagc tggcgggggt gtagagctgg gtgaagtggt tggcgatctt 26280ctgcatcatg attccttttc tggtgatggt gtgttgatgg ttttatcggg tggatgcgac 26340caggatggcg tctacatcga tcatgtcgat catgtcgtgg agttcctcgg cctcattctc 26400ggataggtgg cgccagtcac agtctccgta tacggcgccg tcgagggtga cagtccacaa 26460tggccggatg agccgtatgg cttcttgtac tttagcgtgg tacatgcgac gcaccatatc 26520gagatcgatg tcgtctgaat ggtttccggt gaggctgtgg aggctgaggg ggtcgatttc 26580tgtctgcctg tagagggatg tgaaggatgg tgtgacgagc gtgccatcca tagggtgtgt 26640gctcctttcg gtggtgtagg ggttgttgtg gtttctagag tgtgcgggct gttaccccac 26700tgtcaaggct acgctcattt ggattgagcg tttcatgggg gtgtgtcggg tgtgacagat 26760gtcacttaag cctttattga ctctcccagc gtctcaaatc ttctgggggt aggattatgc 26820agggttggcc ctggtagtcg attctaggga ccttctaggg cgtctcaggg gtatgtctga 26880gtgatagcag gtctggtaga tgacccggca gatctacctt gattttcatg gcaggagtcg 26940aggtgccata tatgggcata gaatctaaac cctcatactg tgtgagatgt atcacactcg 27000cctagtatgg tgtgcactct cgggatcact ctgccgatct ggcgtggagg gtgtagccaa 27060gaaatgccgt ttaaagcctt cgcatggcgc ctaggagcgc cttgcggggt gggggctagg 27120tatttatacc cccagcatat tctgatcgat tctagacgta cccaaaagcc tgatatacga 27180tcaaccatct cagcatagac catcagcccc tatcctggtt agctaagcct acactatgtg 27240gacagtgtgg gataccgtgg gggaagaagg acacggtaaa agaaagaggg gggagcatca 27300gccttcccac ctgaggtact tcagttcacc ttaaggtctt agcacttagc accgagcccc 27360tcaaaggctc ggcatcagcc cgaacaggct cagccctgaa aggggtacac gtcatcagag 27420aaggcttgag agtacgagga gccctagcga cgagtactcg aaagcctgag ggaacaccct 27480cagcactgat gggcctagcg tgttcggaaa ggacacaaga gtacagtgtg acagctatcc 27540gggagtgaaa cccgttctga ctaggggttt cagccttaac caccctcaaa ggttacaaga 27600ctttaagaaa atttaaggaa aagtttaggt ttaatttttg gacctttacc accaaaaaca 27660cccgtttaca cccctcaaac ccgcctatag agccaaatcc accagtttga ctcatcccag 27720gtggggtatg ataggctgga caggtagcca gctggacgca aggccgaaat ccgctgacgc 27780ggctttcacc cttacatcca tcagtctacc aaagacttaa agacctaagg gcttagcgct 27840aaggtgctga tagcttagca ccgagcccct caagggctcg gcatcagtct taaagcctta 27900aacacttcaa gtacatataa aactttaaga gcttaacact taaggttatc aataaacatt 27960aaagctttaa agtcttaaag tacatataaa accttaacag ttaaacgtta aaagctttaa 28020accttaacac ctaagttaag tataaaacct taaaggatta gcacttaagg atataaactt 28080aacatcagtg tttaagactt taaaacttaa aataactatt aagacttaaa gacctataag 28140ctttaaacac ttaaagtaac tataagactt taaaaacctt aagtacttaa agttaaccat 28200cagtcttaaa ctttactatt atacctataa gtcttaaagc ttataggtat aataatataa 28260tataagtatt aaagcttata agttataaaa gttttagaag agctaagggg ttaacttctt 28320tacttctctt ctctctttgg ttctttctct cttctcttct tttcttcatc aggggagaag 28380aggaaccttt taccgtcaac gctgatgggc ttttcgccgt gtgtctcgtg taccaccggt 28440cgcacgctcc cggtttgtac actccccaca ctctgacacc cgtgtccctt tcaggtttgg 28500cgtgttcggc tgaaggcgta cggcgtgtca cgccaacacc cttaacacca ggtaagactt 28560aaagtgcata ttatatgtag aagactttaa aaacctgtca ggtgttcctg ctgagcctgt 28620gtcctacacc gctaggcgcc aagcgctaag ctgtgaaacg cgaacacaca ctcaccccct 28680ttttctttcg tgtccttctc ttttgacaca gctggggggc gatgtgatct ttttcacacc 28740cgttgggggt agtggagaaa acaaccaccc cggcacaaac agaacacccc ctcaaacgaa 28800caaaacaggg cctagaatcg atcggcaggg caccggtaga gtattcatac ccccaacggt 28860tcccaagccg ttacaggagc aatgagaggc tcacaggggc cataggagat caggggacgc 28920gatggcacac accaaccgca cagccagcca agcccaccgg cgctggcggg caagactcat 28980cacccaagcc cgacagcaag gccaaaccga atgcccactc tgcggagcca ccatcgcctg 29040ggacacacac gacctgccaa ccagccccga agccgaccac atcacgcccg tcagcagggg 29100aggactcaac accctcgaca acgggcaaat catctgcaga acatgcaaca gaagcaaagg 29160caatcgcagc gaaccaaaca tcaaactcca acaacaaacc acaaaaacat tgattccatg 29220gtgaaaaacc cgccaacccc caccggggac accccctgca caggcggcaa gacct 29275429153DNABacteriophage 103672 4tcccttttgt ggattgtctg tttgtcgact ttttgtgttg gtggtgagtg ttgtgcagcc 60tgagcttcct gatagtcgtg gatggtgtgg ggagacgcgt cgttggtggc gtgtgtgggg 120tgaggatccg cgtgccgggt ttgtgtctga tgaggagtgg ctgtttctca tggatgctgc 180ggtgattcat gattgtgtgt ggcgtgaggg

tcgcgcggat ttggtggctt cgcttcgtgc 240tcatgtgaag gcttttatgg gtatgttgga tcggtattcg gttgatgtgg cgtctggtgg 300ccgtggtggg ggttctgcgg tggcgatgat tgatcggtat aggaagcgta ggggtgcttg 360atgtctcggg tggtgggttc tcaggttcct cgtcaccgtg tggctgcggc gtattcggtg 420tctgctggcg gtgatgctgg ggagttgggt cgtgcgtatg ggttgacgcc tgatccgtgg 480cagcagcagg tgttggatga ttggctggct gtcggtggta atggcaggct tgcttcgggt 540gtgtgtgggg tgtttgtgcc tcgccagaat ggcaagaatg ctattttgga gattgtggag 600ttgtttaagg cgactattca gggtcgccgt attttgcata cggctcacga gttgaagtcg 660gctcgtaagg cgtttatgcg gttgaggtcg ttttttgaga atgagcggca gtttcctgac 720ttgtatcgta tggtgaagtc gattcgggcg acgaatggtc aggaggctat tgtgttgcat 780catccggatt gtgccacgtt tgagaagaag tgtggctgca gcggttgggg ttcggtggag 840tttgtggccc gttctcgggg ttctgctcgc gggtttacgg ttgatgattt ggtgtgtgat 900gaggctcagg agttgtcgga tgagcagttg gaggctttgc ttcctacggt gagtgctgcc 960ccgtctggtg atcctcagca gatttttctt ggcacgccgc ctggtccgtt ggctgatggt 1020tctgtggtgt tgcgtttgcg tgggcaggct ttgtcgggtg gtaaaaggtt tgcgtggacg 1080gagttttcga ttcctgacga gtctgatccg gatgatgtgt cgcggcagtg gcggaagttg 1140gctggggaga cgaatccggc gttggggcgg cgtttgaatt ttgggactgt gtcggatgag 1200catgagtcga tgtctgctgc cgggtttgct cgggagcggc ttggctggtg ggatcgtggc 1260cagtctgctt cgtctgtgat tcctgcggat aagtgggctc agtctgcggt ggatgaggcg 1320gctctggttg gcgggaaagt gtttggtgtc tcgttttctc gttctgggga tcgggttgct 1380ttggcgggtg ccggtaaaac tgatgctggg gttcatgttg aggttattga tgggctgtcg 1440ggaacgattg ttgatggtgt gggccggttg gctgactggt tggcggttcg ttggggtgat 1500actgaccgga ttatggttgc cgggtctggt gcggtgttgt tgcagaaggc gttgacggat 1560cgtggtgttc cgggccgtgg cgtggtggtt gccgatactg gggtgtatgt ggaggcttgt 1620caggcgtttt tggagggtgt caggtcgggt gtgatcagtc atcctcgtgt tgattctcgc 1680cgtgacatgt tggagattgc tgtgaggtcg gctgttcaga agcgtaaggg gtctgcgtgg 1740ggttggggtt cctcgtttaa ggatggttct gaggttcctt tggaggctgt atcgttggcg 1800tttttggggg ctaaacgtgt tcgtcgtggc cgtcgggagc gtagtggtag gaagcgggtg 1860tctgtggtat gaactcggat gagttggctt tgattgaggg tatgtacgat cgtatccaaa 1920ggttgtcttc gtggcattgt tgcattgagg gctactatga gggctctaat cgggtgcgtg 1980atttgggggt ggctattcct ccggagttgc agcgtgtgca gactgtggtg tcgtggcctg 2040ggattgcggt ggatgctttg gaggagcgtc tggattggct tggctggact aatggtgacg 2100gctacggttt ggatggtgtg tatgctgcga atcggcttgc tacggcgtcg tgtgatgtgc 2160atttggatgc gctgattttt gggttgtcgt ttgtggctgt tatcccccag ggggatgggt 2220cggtgttggt tcgtccgcag tcgccgaaga attgtactgg ccggttttcg gctgacgggt 2280ctcgtttgga tgctggtctt gtggtgcagc agacgtgtga tcctgaggtt gttgaggcgg 2340agttgttgct gcctgatgtg attgttcagg tggagcggcg tgggtctcgt gagtgggttg 2400agacgggccg tatcgtgaat agtcttggtg cggttccgtt ggtgccgatt gtgaatcggc 2460gtaggacgtc gcgtattgat ggccgttcgg agatcactcg gtctattagg gcttacacgg 2520atgaggctgt gcgcacactg ttggggcagt ctgtgaatcg tgacttctac gcttatcctc 2580agcgttgggt gactggtgtg agcgcggatg agttttcgca gcctggctgg gtcttgtcga 2640tggcttctgt gtgggctgtg gataaggatg atgatggtga taccccgaat gtggggtcgt 2700ttcctgtcaa ttcgcctaca ccgtattcgg atcagatgag actgttggcg cagttgacgg 2760cgggtgaggc tgcggttccg gaacgctatt tcgggtttat cacgtctaac ccgcctagtg 2820gggaggcttt ggctgccgag gagtctcggc ttgtgaagcg tgctgaacgc aggcagacgt 2880cgtttggtca gggctggctg tcggttggtt tcctggctgc taaggcgttg gattctcgtg 2940ttgatgaggc cgattttttt ggtgatgtgg gtttgcgttg gcgtgacgct tcaacgccga 3000ctcgggcggc tacggctgat gctgtgacga agcttgttgg tgccggtatt ttgcctgctg 3060attctcgtac ggtgttggag atgttggggc ttgatgatgt gcaggttgag gctgtgatgc 3120gtcatcgtgc cgaatcttcg gatccgttgg cggcgctggc tggggctatt tctcgtcaaa 3180ctaacgaggt ttgatgaatg gcttcgggtg ctatgtcgag gcttgctgcg actgagtatc 3240agcgtgaggc ggtcaggttt gctgggaagt atgcgggcta ttattctgag cttggtcgtt 3300tgtggcattc cgggaagatg acagatgcgc agtatgtgcg tttgtgtgtg gagttggagc 3360gtgccggcca tgatggttcg gcatcgttgg ctgccaggtt tgtgcaagat tttcgccggt 3420tgaacggtgt cgatcctggt ttgattgtgt atgacgagtt tgatgctgcg gcggcgttag 3480ctcggtcgtt ttcgactatg aagattcttg agagtgaccc ggatagggtg aatgacacga 3540ttggtgcgat ggctgcgggt gttaatcggg ctgtcatgaa tgctggccgt gacacggttg 3600agtggtcggc gggtgcgcag ggtaggtcgt ggcgtcgggt tactgatggt gatccgtgcg 3660cgttttgtgc catgttggct acgaggtcgg attatacgac tcgggagcgg gcgcttacta 3720cgggtcatac tcggcgtcat aagcgtgccg gtaagcgtcc gcttggttcg aagtatcatg 3780atcattgtgg gtgtacggtg gttgaggttg ttggtccttg ggaaccgaat agggctgatg 3840ccgcatatca gaggacgtat gagaaggctc gtgagtgggt tgatgatcat gggttgcagc 3900agtcgcctgg caatattttg aaggctatgc gtactgttgg cgacatgaga tgatggtttc 3960cggttgtgtg ccgccggtta tcggtgcaca gggttgtctc ccgcacgggg gtcaacaatg 4020ttgtgttgtt ttccgcaagg agtatagggt taggctatgg ccgatcaaaa agttgaagaa 4080cagaatgttg acaatgatgc tgttgagccc ggaaagggtg gagatgttgt tgatgttgtg 4140aaggatgggc aggctgccgg cgatgatcat gccggtgatg tttccgtgaa ggaggagtct 4200tcttctggca cggattggaa ggctgaggcc cgtaagtggg agtctcgtgc taaaagtaat 4260ttcgccgagt tggagaagct tcgcgcctcg gatggtgatg cggggtctgt gattgatgag 4320cttcgccgca agaatgagga actcgaagac cggatcaacg ggtttgttct tgagggtgtg 4380aagcgcgagg tggcttcagg gtatggtttg tccagtgatg cgatcgcttt cttgtcgggt 4440ggcgataagg agtcgcttgc cgagtctgcg aaagctttga agggtttgat cgaccatagt 4500agtggtggcg tgggtgtgcg ccgtcttgcg gggagtgccc ccgttgatga tgttaaacga 4560cgtgagggtg tcgcgtttgt ggatgctctt gtcaataatt ctaggagatg atttgtgatg 4620gctgacgatt ttctttctgc agggaagctt gagcttcctg gttctatgat tggtgcggtt 4680cgtgaccgtg ctatcgattc tggtgttttg gcgaagcttt cgccggagca gccgactatt 4740ttcggtcctg ttaagggtgc cgtgtttagc ggtgttcctc gcgctaagat tgttggtgag 4800ggcgaggtta agccttccgc gtctgttgat gtttcggcgt ttactgcgca gcctatcaag 4860gttgtgactc agcagcgtgt ctcggacgag tttatgtggg ctgacgccga ttaccgcctg 4920ggtgttttgc aggatctgat ttccccggct cttggtgctt cgattggtcg cgccgtggat 4980ctgattgctt tccacggtat tgatccggct acgggtaagc ctgctgcggc tgtcaagtct 5040tcgctggata agacgaagca tattgttgat gcaaccgata gcgctacggc tgatctgatt 5100aaggctgttg ggctgattgc tggtgccggt ttgcaggttc ctaacggggt tgctttggat 5160ccggcgttct cgtttgccct gtctactgag gtgtatccga aggggtctcc gcttgccggc 5220cagcctatgt atcctgccgc cgggttcgcc ggtttggata attggcgtgg cttgaatgtt 5280ggtgcttctt cgactgtttc gggtgtcccg gagatgtcgc ctgcctctgg tgttaaggct 5340attgttggtg atttctcgcg tgttcattgg ggtttccagc gtaacttccc gatcgaactg 5400atcgagtatg gtgacccgga tcagacgggg cgtgacctta agggccataa tgaggttatg 5460gttcgcgccg aggctgtcct gtatgtggct atcgagtcgc ttgactcgtt tgctattgtg 5520aaggagaagg ctgccccgaa gcctaatccg ccggccgaga actgatctat ttgttgctat 5580aatgttcatg ctgtgtgcag ggggtggtat tgatgggtat cattttgaag cctgaggata 5640ttgagccttt cgccgatatt cctagagaga agcttgaggc gatgattgcc gatgtggagg 5700ctgtggctgt cagtgtcgcc ccctgtatcg ctaaaccgga tttcaaatac aaggatgccg 5760ctaaggcgat ccttcgtcgg gctttgttgc gctggaatga taccggggtt tctggccagg 5820tgcagtatga gtctgcgggt cctttcgctc agactacacg gtctaatact cccacgaatt 5880tgttgtggcc ttctgagatt gccgcgttga agaagttgtg tgagggtgat ggtggggctg 5940gtaaggcgtt cactattaca ccgaccatga ggagtagtgt gaatcattct gaggtgtgtt 6000ccacggtgtg gggtgagggt tgctcgtgcg ggtcgaatat taacggctac gctggccctt 6060tgtgggagat atgatatgac cagttttcct tatggtgaaa cggttgtgat gcttcagccg 6120actgttcgtg tcgatgatct tggtgacaag gtggaagact ggtctaagcc tgtcgagact 6180gtgttccata acgtggccat ctatgcttcg ttgtcgcagg aggatgaggc cgcggggcgt 6240gactcggatt atgagcattg gtcgatgctt ttcaagcagt ctgttgtggg tgccggttat 6300cgttgtaggt ggcgtattcg gggtgttgtg tgggaggctg acgggtctcc tatcgtgtgg 6360catcacccca tgtctggctg ggatgcgggc acgcagatca atgtgaagcg taagaagggc 6420tgatgggtag tggctcagga tgtgaatgtg aagctgaact tgccgggtat tcgtgaggtg 6480ttgaagtctt ctggggtgca ggctatgttg gctgagcgtg gcgagcgtgt caagcgtgcg 6540gcctcggcga atgtgggcgg taacgctttc gatagggccc aataccgtaa tggtttgtcg 6600tcggaggtgc aggttcaccg tgttgaggct gtggcgagga ttggcactac ctataagggt 6660gggaagcgta ttgaggcgaa gcatggcacg ttggcgaggt cgattggggc tgcgtcgtga 6720tcgtttacgg tgatccgcgt gtgtgggcta aacgcgtgct caaggatgat ggctggctgt 6780caggtgtgcc ttgtgtgggg acggtgcccg atgattttac gggtgacctg atttggttgg 6840cgttggatgg tggcccgcag ttgcatgtgc gtgagcgtgt ttttttgcgc gtgaatgtgt 6900tttcggatac gccggatcgt gctatgtcgt tggcgcgtcg tgttgaggct gtgctggctg 6960atggtgtgga tggtgaccct gtggtgtatt gtaaacggtc tactggccct gatttgctgg 7020ttgatggtgc acgttttgat gtgtattcgc tgttcgagct gatatgtagg cctgtcgaat 7080ctgaataagc ttattgtttt tgttttaatg taattgtttg atatttaatg ggggttgtga 7140tggctgcaac acgtaaagcg tctaatgttc gctctgctgt tacgggtgac gtttatattg 7200gtgccgcgca cgcgggtgac actattgatg gtgtgaagac ggttcctgac ggtcttaccg 7260ctttagggta cctgtctgat gacgggttta agattaagcc tgagcgtaaa acggatgatt 7320tgaaggcttg gcagaatgcg gatgttgttc gcactgtggc tactgagtcg tctatagaga 7380tttctttcca gctgatcgag tctaagaagg aggttatcga gctgttttgg cagtcgaagg 7440ttactgccgg atccgattcg ggttcgttcg atatttctcc gggtgccacg acgggcgtgc 7500acgctttact gatggatatt gttgatggtg atcaggttat tcgctactat ttccctgagg 7560ttgagttgat cgatcgtgac gagattaagg gtaagaatgg cgaggtttac gggtatggtg 7620tgacgttgaa ggcgtatcct gcccagatta ataagaaggg tgatgcggtg tctggtcggg 7680ggtggatgac ggctttaaaa gctgatactc ctccggttcc gccttctccg aagcctcagc 7740cggatccgaa tccgccgtct aataactgat acacgagttt aagggattgt tgatagatga 7800gtgacactgg tttcacgttg aagattggtg accgtagctg ggtgttggcg gatgcggagg 7860agacggctca ggctgttcct gcccgcgtgt ttcgccgtgc cgccaggatt gcccagtcgg 7920gggagtctgc ggatttcgcc caggttgagg tgatgttttc tatgctagaa gcggccgcct 7980cggctgacgc ggtggaggct ttggaggggc ttcctatggt tcgtgttgcc gagattttcc 8040gtcagtggat ggaatacaag cccgaccaga aagcagcctc cctgggggaa tagtttggct 8100ccacggcctg attgatgatt atcgtggggc catcgaatac gatttccgca ctaaatttgg 8160tgtttctgtt tatagtgttg gtggcccgca gatgtgttgg ggtgaggctg tccggctggc 8220tggcgtgttg tgtaccgata cgtctagcca gttggcggcc cacctgaatg gttggcagcg 8280cccgtttgag tggtgcgagt gggctgtgtt ggacatgctg gatcattaca ggtctgctaa 8340tagtgagggg cagccggagc ctgtggcgag gcctacggat gagcgtaggg cccggtttac 8400gtcggggcag gtggacgata ttttggcgcg tgttcgtgcc ggtggcgggg tgtctcgcga 8460gattaatatt atggggtgaa tagtgtatgt ctggtgagat tgcttccgca tatgtgtctt 8520tgtatacgaa gatgccgggt ttgaaagcgg atgttggtaa acagctttcc ggggtgatgc 8580ctgcggaggg tcagcgttcg ggtagcttgt ttgctaaggg catgaagttg gcgcttggtg 8640gtgccgcaat ggtgggtgct atcaatgttg ctaagaaggg cctcaagtct atctatgatg 8700tgactattgg tggcggtata gcgagggcta tggctattga tgaggctcag gctaaactta 8760ctggtttggg tcacacgtct tctgacacgt cttcgattat gaattcggct attgaggctg 8820tgactggtac gtcgtatgcg ttgggtgatg cggcttctac tgcggcggcg ttgtctgctt 8880cgggtgtgaa gtctggcggg cagatgacgg atgtgttgaa gactgtcgcc gatgtgtctt 8940atatttcggg taagtcgttt caggatacgg gcgctatttt tacgtcggtt atggcgcgcg 9000gtaagttgca gggcgatgac atgttgcagc ttacgatggc gggtgttcct gtactgtctt 9060tgcttgccag gcagacgggt aaaacgtcgg ctgaggtgtc gcagatggtg tcgaaggggc 9120agattgattt tgccacgttt gcggctgcga tgaagcttgg catgggtggt gctgcgcagg 9180cgtctggtaa gacgtttgag ggtgctatga agaatgttaa gggcgccctg ggttatcttg 9240gtgctacggc tatggcgccg tttcttaacg gcctgcggca gatttttgtt gcgttgaatc 9300cggttatcaa gtctatcacg gattctgtga agccgatgtt tgctgccgtc gatgctggta 9360ttcagcgtat gatgccgtct attttggcgt ggattaatcg tatgccgggc atgatcactc 9420gaatgaatgc acagatgcgc gccaaggtgg agcagttgaa gggcattttt gcgagaatgc 9480atttgcctgt tccgaaagtg aatttgggtg ccatgtttgc gggtggcacc gcagtgttcg 9540gtattgttgc tgccggtgtg gggaagcttg tcgtagggtt tgccccgttg gcggtgtcgt 9600tgaagaatct gttgccgtcg tttggtgctt tgaagggtgc cgccgggggg cttggcggcg 9660tgtttcgcgc cttgggtggc cctgtcggta ttgtgatcgg cttgtttgct gccatgtttg 9720ctacgaacgc ccagttccgt gccgctgtta tgcagcttgt ggctgtggtt ggccaggcgt 9780tggggcagat tatggccgct attcagccac tgttcgggat tattgctggc gtggttgcca 9840ggttggcgcc agtgttcggc cagattatcg gtatggttgc tggtttggct gcccaactgg 9900tgcctgttat tggtatgctt attgcccggc tggttcctgt tattacccag attattggta 9960tggtaaccca ggttgctgcg atgattttgc ctatgctgat gccggttatt caggctgttg 10020ttgctgtgat acggcaggtt gttggcgtga tcatgcagtt ggtgcctgtt ttgatgcctg 10080tgattcagca gattttgggt gctgtcatgt ctgttttgcc gccgattgtt ggtttgatac 10140ggtcgctgat accagtcatc atgtcgatta tgcgtgtggt ggtgcaggtt gtttcggttg 10200tgttgcaggt ggtggcccgt attattccgg ttgttatgcc gatttatgtt gcggtgattg 10260gattcattgg caagatttat gctgcggtta tcggttttga ggctaaggtt attggcgcta 10320ttcttcgtac tattacgtgg attgtgaatc atttagtgtc tggcgtcagg tctatgggca 10380cggccatcca gaatggctgg aatcatatca aatcgtttac gtcagcgttt attaacggtt 10440tcaaatctgt tatttctggc ggcgtgaacg ctgttgtggg gtcttttgcc cggcttggtt 10500cttcggttgc ctcccatgtg aggtctggtt ttaacgcggc ccggggtgct gtttcttctg 10560cgatgaattc tatccggggt gttgtgtctt cggtggcgtc tgctgttggt gggtttttca 10620gttcgatggc gtctagggtt cgtagtggtg ctgtgcgcgg gtttaatggt gcccggagtg 10680cggcttcttc tgctatgcat gctatggggt ccgctgtgtc tagcggggtg catggtgtgc 10740tgggtttttt ccggaatttg cctggcaata ttcggcatgc tctcggtaat atggggtcac 10800tgttggtgtc tgctggccgt gatgtggtgg ccggtttggg taacggtatt aagaatgcta 10860tgagtggcct gttggatacg gtgcgtaaca tgggttccca ggttgctaat gcggcgaagt 10920cggtgttggg tattcattcc ccgtctcggg tgtttcgtga ccaggttggc cggcaggttg 10980ttgccggttt ggctgagggg atcaccggga atgcgggttt ggcgttggat gcgatgtcgg 11040gtgtggctgg acggcttccg gatgctgttg atgcccggtt tggtatgcga tcgtctgtgg 11100gctcgtttac accgtacgac cggtatcggc gtgcgagcga gaagagtgtt gtggtgaatg 11160tgaatgggcc tacttatggg gatcctgccg agtttgcgaa gcggattgag cggcagcagc 11220gtgacgcttt gaacgcgttg gcttacgtgt gattgagggg gtgttgtgca tgtttattcc 11280tgacccgtct gatcgttctg gtttgactgt gacgtggttt atggatccgc tgtttggcga 11340cgagcgtgtg cttcatttga cggattatac gggtgcgtct cctgtcatgt tgttgaatga 11400ttcgttgcgc ggtttgggtg ttcccgaggt tgagcatttt tctcaaacac atgttggggt 11460gcacggctcg gagtggcgcg ggtttaatgt gaagcctcgc gaggtgacgc tgccggtttt 11520ggtgtcgggt gttgacccgg atccggatgg cgggtttcgt gacggttttt tgaaagccta 11580tgacgagttg tggtcggcgt ttccctcggg cgaggtgggg gagttgtcgg ttaaaacccc 11640gtctggtcgt gagcgtgtgt tgaagtgccg gtttgattcg gtggatgaca cgtttacagt 11700tgatccggtg aacaggggct atgcgcgcta tctgttgcat ttgacagcgt atgacccgtt 11760ttggtatggg gaggagcaga agtttcgttt tagtaacgcg aagttgcagg attggttggg 11820tggcggccct gtcggcaagg atggcacggc gtttcctgtg gtgttgacgt ctggtgttgg 11880ttctggctgg gataatctgt ctaataaggg tgatgtgcct gcgtggcctg ttattcgtgt 11940tgaggggcct ttggagtcgt ggtctgtgca gattgatggt ttgcgtgtgt cttcggatta 12000tcctgtcgag gagtttgatt ggatcactat tgatacggat cctcgtaaac agtctgcgtt 12060gttgaacggg tttgaggatg tgatggatcg tttgacagag tgggagtttg cccctatccc 12120gcctggcggt tcgaagagtg tgaatattga gatggttggt ttgggtgcca ttgttgtgtc 12180ggtgcagtac aggtttttga aggcttggtg aatagttgat gactgatctg gttccgcatg 12240taacattgtt tacaccggat tatcgccgtg tggcgcctat caattttttt gagtcgttga 12300agttgtcgtt gaagtggaat ggtttgtcga cgctggagtt ggtggtgtct ggtgatcatt 12360ctaggcttga cgggttgact aggccgggtg cacggctggt tgttgattat ggtggtggcc 12420agattttttc tgggcctgtg cgtcgggtgc atggtgtggg tccgtggcgt tcttcgcggg 12480tgactatcac gtgtgaggat gatatccgcc tgttgtggcg tatgttgatg tggcctgtga 12540attatcgtcc tggtatggtt ggtatggagt ggcgtgccga cagggattat gcccactatt 12600cgggtgcggc ggagtcggtt gctaagcagg tgttggggga taatgcttgg cgttttccgc 12660ctggtttgtt tatgaccgat gatgagagtc gtggccgcta tattaaggat tttcaggtgc 12720ggtttcacgt gtttgccgat aagttgttgc cggtgttgtc gtgggctcgg atgactgtca 12780cggtgaacca gtttgagaat gcgaagtttg atcagcgtgg tttggtgttt gattgtgtgc 12840ctgctgtgac ccggaagcat gtgttgactg ccgagtctgg ttcgattgtg tcgtgggagt 12900atgtgcgtga cgcccctaag gctacttcgg tggtggttgg tggccgcggc gagggtaagg 12960atcggctgtt ttgtgaggat gttgattcga tggccgaggg ggattggttt gatcgtgtcg 13020aggtgtttaa ggatgcccgt aacacggatt ctgaacatgt gcatctcatc gatgaggctg 13080agcaggtgct gtccgagtcg ggggccacgt cggggtttaa gatcgagttg gctgagtcgg 13140atgtgttgcg gtttgggccc ggcaatctga tgccgggtga tttgatttat gtggatgtgg 13200gttctggccc tattgcggag attgttcggc agattgatgt ggagtgtgta tcgcctggtg 13260acgggtggac gaaggtgact cctgttgctg gggattatga ggataatccg tcggccctgt 13320tggctcgccg tgttgccggt ttggctgccg gtgtgcggga tttgcaaaag ttctaaaaag 13380attaggggtt tgttgtgggt attgtgtgta aagggtttga tggtgtgttg accgagtatg 13440attgggctca aatgtctggt ctgatgggta atatgccgtc tgtgaagggc ccggacgatt 13500ttcgtgtcgg cacgacgatt cagggtgcca cagtgttgtg tgaggtgttg ccggggcagg 13560cttgggctca cggggtgatg tgcacgtcga atagtgttga gacggtgacg ggccagcttc 13620cgggccctgg tgagacccgc tacgactatg tggtgttgtc tcgggattgg gagcagaaca 13680cggccaagtt ggagattgtt cccggggggc gtgcggagcg tgcccgggat gtgttgcgtg 13740ccgagcctgg cgtgtttcat cagcagttgt tggctacttt ggtgttgtcg tctaacgggt 13800tgcagcagca gctggatcgg cgtgctatag cggctagggt tgcgtttggg gagtctgctg 13860cgtgtgatcc tacccctgtg gagggtgacc gggtgatggt tccttcgggg gctgtgtggg 13920ctaaccattc gggtgagtgg atgttgttgt cacccaggat agagacgggt tctaagtcga 13980tcatgtttgg cgggtcggct gtgtatgctt acatgatccc gtttgagcgg ccgtttagta 14040gtgcgcctgt tgtggtggcg tctatggcta cggcggctgg gggtacgcag cagatcgatg 14100tgaaagccta caatattact aataaggatt ttagtttagc gtttattacg aatgatggtt 14160ctaagccttc tggtgtgcct gcggtggcta actggattgc tgtgggcgtg tgaccgggct 14220gttgttgtgg cggatggtgt gatgttgggg gggctgtggt gtcgtggttt actcctgcac 14280tggtggcctc tatttgtacc gcgttggcca cgattttggg ttctgttcag gcggtcacat 14340cccgttctag gcggcgtttg cggcggctgt cggctcaggt ggatgcgatg gaagagtata 14400cgtggggtgt tcggcgtgag gttcgccggt ttaactcgcg gcttcctgac gaggtggagc 14460ctatgcgtct tcctgatgtg cccgagtttt tgaaagatac tgttgatggt ggaggtgagt 14520agggttgagg gagttggagg aggagaagcg gcagcgccgc tcgtttgaga aggcttccct 14580gatactgttg ttcctgtcgc ttgtactgtt ggcggtggtt gccgggggtg ctttacggta 14640cgggtctgtg gcttcccaaa gggattcaga gcaggctaaa gcccagtcga atggtacagc 14700cgctaaaggt ttggctgccc gtgtgaagca ggcgtgtgcc tctggcgggc aggagtctgt 14760gcggcttcac cagtctggct tgtgtgtgga tgctgtgcgt gttgagcgga gtgtgcatgg 14820tgtgccgggc ccggccggtg agcgcggccc gcaaggccct gcaggtgttg acggccggga 14880tggtgttaat ggttcggctg ggctggttgg ccctgttggt ccgcagggtt ctcccggttt 14940gaatggtgtg aagggtccgc agggttctgc cggtgcgaac ggatcggatg gccatgatgg 15000tgttccaggt cgtgcaggtg ctgacggtgt gaacggcgct gatggtcgag atggtcctgc 15060cggtaagcgc ggtgatgtgg gcccttcagg tccggccggc ccgcaaggtg cacagggtga 15120acggggtcct attgggcctc agggtccgca gggttctgcc ggtgcgaacg gatcggatgg 15180ccatgatggt aaagatgggc gttctgtggt gtctgtgtac tgttccgggg gccgcctggt 15240tgtgaaatat agtgacggta tggtttctac

catatcgggt tctgtggcct gtgagggtgt 15300gaaaccgtcg cctatagtga ctatatcatc ccacaaatag aaaggagtgg ctgtgatggt 15360agtgtttggt ggtggtgtgt ggtgaggttt attcctgctg cgcatcattc tgccggctcg 15420aatagtccgg tgaatagggt tgtgattcat gcgacatgcc cggatgtggg gtttccgtcc 15480gcttcccgta aggggcgggc ggtgtctacg gcgaactatt tcgcgtcccc atcggcgggc 15540ggttctgccc attatgtgtg cgatatttcg gagacggtgc agtgcttgtc ggagtctacg 15600attgggtggc atgccccgcc gaatccgcat agtttgggta tcgagatttg cgcggatggg 15660ggttcgcacg cctcgttccg tgtgccaggg catgcttaca cgagggagca gtggctggat 15720cctagggtgt ggcctgcggt ggagaaggct gccatcctgt gtagacgttt gtgtgacaaa 15780tataatgttc cgaaaaggaa gcttagtgca gccgatttga aggctggcag gcggggtgtt 15840tgcgggcatg tggatgttac ggatgcgtgg catcagtcgg atcatgacga tcctgggccg 15900tggtttccgt gggacaaatt tatggctgtg gtgaatggcc acggcggcgg ttcaagtagt 15960gaggagttaa cggtggctga tgtgaaagcg ttacataatc agattaaaca attgtctgct 16020cagcttactg gttcggtgaa taagctgcat cacgatgttg gtgtggttca ggtgcagaat 16080ggtgacctgg cgcgccgtgt tgatgccttg tcgtgggtga agaatccggt gacggggaag 16140ctgtggcgca ctaaggatgc cctgtggagt gtctggtatt acgtgctgga gtgtcgtagc 16200cgtattgaca ggcttgagtc tgctgttaac ggtttgaaaa agtgatggtg gtttgttgtg 16260ggtaaacagt tttggttagg tttactggag cgggcggcta agacttttgt gcaaacgttt 16320gttgctgtgt tgggggtgac ggcgggtgtc acctatacgg cggagtcgtt tcgcggtttg 16380ccgtgggagt ctgccctgat cacagctacg gtggctgcgg tgttgtcggt tgctacatcg 16440tttggtagcc cgtcgtttgt ggctggcaaa cctaaaacca cgcctgtgga tgcgggtttg 16500gttccaccgg atgatggggg cttggttgag ccgcacatgg ttgatgtgtc ggatcctggc 16560atgatcgagc cgattgatga tgcggatgtt gtcggctatg tgccgaggcg tgccgccgag 16620tcggaggttg acacggtaga gtctactgtt gcataattga atatgtgtgt gccccagcgg 16680tgctgccacg atctgtggtg gttgccgctg gggcactatt tttgtgtcta tagtattcta 16740tgattcgttg ttgttgatgg tttcttcgat cagctggtcc aggtggaggc aggtagagat 16800cgtttcgttg gcctggtgca gaacatcctg gccgataaca tttttgtggt tgtcgcggtg 16860gcagatgatt gactgcatga tatcgtcggc ttccgattgt agtagtttgg tttggtatgc 16920gattcctgcc agccaatcta tggcttcctg gcttgcccgt gtgtcgtctg gaatgccacg 16980ggtgttgctg ttgtttgggt atcctgcact gtcgcagtcc cacaagattt cgctgcactc 17040gtctagcgtg tcctggtcga tagcaaggtt gtcgaggctg acttctttga cggtaaggtt 17100cacgttgtcg agtgagatgg gtacacggta ctggttttcg acaccgtcaa caatgttttg 17160cagctgttgc atgttggttg gctgttgttg gatgattcgg tgtactactg ttttgagggc 17220agtgtagggg atattggttg tgttgttcat ggttttatcc catccctgtg ttgtcgtcgt 17280tgccgtcttg gtagtatcga ctgtttgcgt atcctgtgag ggtgatgagt gtttggtctg 17340cccactgttt caccgtctgc cgggttactc cgagtcgttg ggctgccacc gaataggttt 17400ggtcgtaccc gtatacttca cggaatgcgg ccaggcgtgc caaatgtttt cgctgtttgg 17460atggctggca ggtgagggtg tagtcgtcga tggcgagctg taaatcgatc atggtaacga 17520tgttgttgcc gtggtgttgt ggcgcggttg gtgggggtgg catgcctggt tcgacggagg 17580gtttccatgg gcctccgttc cagatccatt gggcggcttg gatgatgtcg gcggtggtgt 17640aggttcggtt cactggtcat cccctgaata ggttgtcgag gttgtctggg ttgctggtgt 17700tggtggtgtc gaatcgtccc acacagtggc agtagtcgta catgagtttg ataatgtgtt 17760ggtggtcgcc gaggtaggtg tttccgctga tactgtaggt ggctgtgccg tctttactga 17820tggtgtattt ggcggtgatg gtttcgggtg tttctgtgtt ggtgatgatg gcggtggtgg 17880tggcgcctac tgtttgtagc ctggtggttt gggtgccgtc gtcgaggatg gttgtgacca 17940tggtgtgtgt tctcctttta aatgcttgtt tggttgtcgg ctagatgaat gatatcggat 18000aaaggtttcg gctggtctag gtgttgtatg gttttgttgg ctagccgttt ggctaccctg 18060tagcacattt tggtgtagtg tttgttgtct aggttgtggt attgttcccg caccgcaata 18120tatagtaggg agtcttggta gaggtcgtct gcactgattg cggggtagtg tccggctgtt 18180ttggtgcatg cccggtggag tgtgcgtaga tgatggtctg tggcccacac ccacgatgcg 18240gtggtggcta ggtcggcttt tgttggtcgt ctgctcatag catctctttc atctggctat 18300ctggtagttg tttggtgttt tgttgttgat agtgtagcac acgagtccgg ggtttccggt 18360ggtgcctgtg cggtgccgga accatgtgga ttcgccttcc atggatgggc attggatgaa 18420ggtgcgttgt ccttgctcag agatttcgag gtggtgccgg tgcccggcca tgagaatatt 18480agatacggtg ccgttgtgga attcttggcc gcgccaccat tcgtattgtt tgccggtttt 18540ccattggtgt ccgtgggcgt gcaggatttg tgtgcctgcc acatcaacgg tggtggtcat 18600ttcgtctcgg ctggggaagt ggaagtgaag gttggggtat tggttgttga gctggtaggc 18660ttctgcgatg gcgcggcagc agtccacgtc gaaggagtcg tcgtaggtgg tgacgccttt 18720gccgaagcgt acggcttctc cgtggttgcc ggggatggat gtgatggtga cgttggcgca 18780gtggtcgaac atgtggacga gttgcatcat ggccatgcgg gtgagcctga tttgttccgt 18840caagggtgtt tgtgtgcgcc aggcgttgtt gccgccttgt gacacgtatc cttcgatcat 18900gtcgccgagg aaggcgatgt ggactcgttc gggtttgcct gcctgttgcc agtagtgttt 18960tgcgactatg agggagtgca aatagtcgtc ggcgaagtgt gctgtttctc cgccggggat 19020gcctttgccg atttggaagt ctcctgcccc gatgacgaag gccgcagtgc tgtagtcggt 19080gtgggtgttg tcggctggtt ttgggggtgt ccatttggct agtttatcga cgagttcgtc 19140tacagggtag gggttggttg cgggttggtg gtcgatgatt ttttgtatgg atcggccggt 19200ttctccgttc ggtaaggtcc attcggagat gcgtgtgcgg cgtacagtac cattggctag 19260attgtcgtcg atggtgtcga tggcgttgtc gtggttggct agctgtgtga gtagccggtc 19320tatattgtct atcactggtt ttcctcttct gtttgtgggg tggtgttggc ttgtttgcgg 19380cgatagtctt tgatgacggt ggcggagatg gggtatccgg cttgggtgag ctgttttgct 19440agccatgagg cggggatggt tttgtcggcg aggacgtctg cggctttgtt gccgtagcgt 19500tggataaggg tttcagtttt ggttgccatg atgtcctagg ggttgtgtgg tgggctgcca 19560tcctgtgcgg cagtcgccgt cgtgtcctgg tttgcgtgtg caccatgaga cttcgccggc 19620attgtggatg atggcacggc cgcatatgac gtcatgtagg tgttcgggaa acttatcgtt 19680gttgttgtcc ccgtacatgt cgatcaagtg ttgggtttta gtaaccatca tgtctcctat 19740gtgtgaaaga gtgtgcaaat actatgctgg tgtcatggat gtttatgcgg gtatggtttt 19800catcaccttg ctgaacgtta cttggttact gtacatcatc tgggtgattt cctgatccgt 19860tttgtcgggg tgctgttttc gcaggtttgc ccattggcag gcgttgtcgg tttcttgctg 19920gagccgggtg agattgtttt cggtgatgat ttgtttccac attgtccacg agacgtcgag 19980tcgtttgagc atgtcgatgg ctggcacgtt gaaggagttg aggaagagta tttcctccgt 20040gtagtagtct ttttcgtatt ggtcccatcc gcttcggtgt ctgttgggct ggtttttggg 20100gtaggcttcc cggcatactt tgtgcaaacg tttggccatg tctttgggta gcctaatgtc 20160ggggttggcg cggatcatgg atcgcatccc atcataggtg gtgccccagg tgtgcatgat 20220atgtagtggg tcttcaccat cagcccattt ttctgcacag atggcgaggc ggatacgcct 20280cctagtggcc ttactcgtgt cgcggcggcc ggggatgggg catgtgtcga gggggtccat 20340gatgcttttt atgcctttct tggagtgatg ttttgtttgt ctggttttat tgtagcactg 20400tgtctagtgc ttgtgtcaac cctgtttttc cggcctgcag ataggtgtct gtgacatccc 20460ccagggtgag gggtacgtgt atggcttggg ggagtgccgt ctggatggtt tgtgccatct 20520ggtcgcctgc tttgtcgggg tcggaccaga tgtagatgcg gtcgtagcct tcaaaaaatt 20580tggtccaaaa gttttgccac gaggttgcgc cgggtagggc tacggccgac catccgcatt 20640gttcgaggat catggagtcg aattcgcctt cgcaaatgtg catttcggct gccgggttgg 20700ccatggcggc catgttgtag atggagcctg tgtcccctgc cggggttaga tatttggggt 20760ggttgtgggt tttgcaatca tgctggagtg agcagcggaa acgcattttt cgtatttcgg 20820ctggctcccc ccagacgggg tacatgtagg ggatggtgat gcactggttg tagttttcgt 20880ggcctgggat ggggtcattg tcgatgtatc caaggtggtg gtagcgggct gtttcttcgc 20940tgatgcctct tgctgagagg aggtcgagta tgttttcgag gtgggtttcg tagagggctg 21000aggctttctg gattcggcgg cgttccgcaa tgttgtaggg ttgtaggctg tcgtacatta 21060gggttttctt tctctagttg ttgtttcagt tgggcgagtc cgcctccgat accgcatgtg 21120tggcagtacc agacgccctt gtcgaggttg atgctcatgg agggctggtg gtcgtcgtgg 21180aacgggcaga ggatgtgttg ctcgttcctg gaaggattgt accgtatctg gtgggtgtcg 21240aggaggcggc gggtgtcaga ggtgtgggag gagctcgttg agggttgata ccacataggc 21300ttcgctccag ggtttgttgc gctgtttcat gacgacgagt ccgatggtgg aattgttttg 21360tttgtttcgg tgtgtttcgt agttgcgtgc ctcccggctg gcttgtttca cgaattcggc 21420gaggtgtgcc tgtccggctt tcgcctcgat aatgtaggtt ttgttgccgg ttgtgaggat 21480gaggtcgcct tcgtcttcgc ggccgttgag gtggaggcgt tctatatcat ggccggtgtc 21540gcgtagctgg tggaggagtc tggtttccca ttcggctccg gctcggcggt tgcgtgcctg 21600ttgtgtcgac atgatagtcc tttgtggtgt tcggtcatgt tccatggctg tttttctgcg 21660aggggcccga agaatgtgta ttcggggtag gctcgtagtc gttcgtatcg ggttccgtct 21720gggctggatt tgcctgtgcg ctgtttcaac actgcgatgc gtgcctctgc cggtatcgtg 21780agcccgttgc cgttgtcctc gccaccataa agtgagactc cgaggatgag ttgtggtttt 21840tcggagaggc cgtttttgat ttccctgcgt gctggcgggt gttcgatgtc ggttccggtt 21900ttgtcggttg cgtggtgtgt gacaataatg gtggagccag tatccctgcc caatgctgtg 21960atccattgca tggcttcttg ctgtgcctgg tagtcggatt cgcagtcttg gatgtccatc 22020aggttgtcga tgacgatgat gggtgggaag gtgttccaca tttccatgta ggcttgcaat 22080tccatggtga tgtctgtcca tgtgatgggt gactggaatg agaatgtgat gtgttggccg 22140tggtggatgc tgtctcgata gtattctggc ccgtagtcgt cgatgttttg ttgtatctgt 22200gtggtggtgt gttgggtgtt gagtgagatg attcgtgtgg aggcctccca gggtgtcatg 22260tcccctgata tgtagagggc gggctggttg agcatggcgg tgatgaacat ggctagccct 22320gatttttggc tgccggaccg ccccgcaatc atgacgagat cccctttgtg gatgtgcatg 22380tccaggttgc ggtagagggg ttctagttgt ggtatgcggg gcagctcggc tgcggtttgg 22440gaggctctct cgaaggatcg ttgtagagag agcatcggga ccttatctat ctattggttg 22500gatgtgtatt ggtggtcaga tggagtcgat atcgatgtca gtagaggctg tggtgtcgtc 22560tagctggccg ttatcgcgct tgtctacgta ttcggccacc ttatcgtaga tggcgtcgtc 22620taatggtttg agcacaaccg cgttgaagcc gtttttggtg cgtacggtgg cgagtttgaa 22680ggcctgctcc tcgccaaggt aggtttctag atcgcggatc atggagtggg ggcggtcgtt 22740gttgccgcgt gctttctcga taatggcgtt ggggatggtt tctggggtgc cgttgttgag 22800atcgtctagg gtgtggaaga ttgtgacatc agcgtagatg cggtctgcga cctgtccacc 22860gtagccttcg gtgttgtgtt cgacgtcgtg gactttgaag gcgatggcgg tggcgtcctg 22920gtttcgggag gggttgaaga aggtgctgtt actgttgttg tttcggtagt ttgcgagtcc 22980cattgttgtt tcctttactg tttgtgttgt tttgtttgtt ggtttgtgtc ggtttatcgg 23040gtgaggctgt ttcgtttatt ccggaaagct tcggacacgt cactgttact agtgatgatc 23100tttttgtact gtttcagaag gtcggctagc tgtgccttgc ttgtggcatt gttaattttg 23160tctatgacga tgctgttttc gtttgatgcg atattgttta cgtagtcttt ggcggcttgg 23220ttgtatcggt cttggaggat gatggatgct gtggcgatca gtgttgccag gtcccagttc 23280cttgccgcgg agctgttttt gagtccgcct aacaggtcga tgatagtctt ctttacctgg 23340tcggcggtgt ctccgcggat gacggtccat ggggcggcgt agtcgcctcc gtatttgagt 23400gtgacggtga atcggtcttc gtctgtgttg tcggtcactg gtgctccttg tcttcttttg 23460ttggggctgt gatggtggtt tctatagggt acctgtaggc atctttcccg ttgacagccc 23520agcaggcgtc ctggacgggg cagcctttgc agagtgctgt gacgtggggt acgaatatgc 23580cttggctgat tcctttcatt gcttgactgt acatggatga tacatgccgg taggtgttgt 23640tgtcaagatc gtacagttcg gtggccgttc cctgcttggc ggactgtttg tctgttttgg 23700ttgatgcggg tgtccaaaac atgccttttg tcacatcgtt gccgtgttgt tctagcatgt 23760acctgtatgt gtgcagctgc atactgtcgg cgggtagacg gccggttttg aggtcgagga 23820tgaaggtttc gccggtgttg gtgtcggtga aaacgcggtc gatgtagcca acgatctggg 23880tgccgtcctg gagggtggtt tctaccgggt attcgatgcc cggctcgccg tcgataacag 23940cgatagcata ttctgggtgg ttgctcctcc atgttttcca gcggtccaca aaggtggggc 24000cgtaaaccat ccaccagtcg tagtctttct tgtgtggccc gcccgactcg cacatgtttt 24060tgcatattct gccggagggt ttgatttctg tgccttcgga ttcggcgagg gcgacttggg 24120tgtcgaaaat gtttttgaag gatgcaagtt tgtctggcag tgcagggtat tcggcgggat 24180tgtacaggtg taggtcgtat tgttcggtga tgtggtgtat ggcgcttccg gcgatggtgg 24240cataccaggt gtggtgttgg gcatggtagc cgtgggatag gcgccatttt tctccgcatt 24300cggcccactg tgacagtgat gagtaggaga tgtggcctgg atggttgatg gttttcgggt 24360attgtgctag aggcattact ggtcgccttt gtgggtgttc catgggttgc gggtgtcttg 24420gccggcattg tgttgctggt atgcgaggag tgcgaggcag tgccaggcag catgtgccag 24480atgcggcaaa tgtgattcgt ggtcgaggtt gttgccttgc tgccatgata gtaggtgccg 24540gtagagggcg tcaacgctgt ggctccacgg gtatcctccg gtccagttgt tgtcgccgta 24600tttggtggca ccgtatccgg ctacttcgcc tagggcgtga agggatgcgg ggtcgatgag 24660ggagagcctg cagagtttca attcttttcg ggcaccgctg ttggggtcgg tgtacatgcg 24720ggtgggctca tccatgagat gtgtgctcct taagggtggg ttactggttg ttgtgggcga 24780gtgctactgc gagaataatg atggcgaggg tttcagcgat cagtatgggt gttgtgatca 24840tttgctgtct ttgggctggt aggtgagggt tgaggcaccc aggagggtgg cgagggcgca 24900tgcggcgatg atggcgaggg ctgccttgtg tggggtgctg gttgcgtaca tccatgtgat 24960gatgccgcct tggatccagg ctaggctggt gaagaacgtt tcgtaactgt gtagctcaat 25020gttgttgttg ggtgtgttca tgcttgctcc tgaagaatgg tgttgatggt tttataaatg 25080ttgtacaggt cggtttcgat agataacagt tggttgattt ggtggtcgag gttgatgtct 25140gggttgaggg tgttgatgcg ggaggcgata tcggtggctg tgcgtagtgt gccgccggtg 25200tggtgaataa tgtgtgccgt gtcggcgagt ccggtggtga cagcgtagtg ggagaggata 25260ggcatagcgg gggaatgttc cttggcgggt tactgttgcg ggttgatgtt gaggtcggtg 25320acgtgcgggt ggtcttctgt tccggtgacg aggcagtgga cggtgacggg tagtttggat 25380gcgccgggct gtttcatggt ggcgccgtag acgatgctga atgtgtcttt accgatggtt 25440ttgtggagtt ggaggtcgat gtcggggttg ccgttccagt tgacgccttg tgctgcggcc 25500tgttgttcgg ctttgcggtt gcaggtgtgt gctgccgtga tcatggtgag tccggttgcg 25560gtttcttcac cccttgcttg ggcttgcttg tgggttttgg cctgctcggc ttgtagggat 25620cgggtggcgg ctgcctgccg tgccgctttc tcggctttgc gctgttgggt agtcttgggg 25680gtccattcgg tgttggctgt ggtggcctgt ggggcgggtt gtgaggcgag tggcggattg 25740tcgtctgggg ctggcaggaa ggatgcggcg gcaatgatgg cggctgtgat tccggcgatg 25800gtgtagccgt ttttcttgtt catgactgtt gtcccctttc cggggtgttg ttcgttgctg 25860acatgattaa tacttccagt gactggacct catgtcaaga ctgcgctcaa atgttgtgag 25920cgtttcctgt atggttagat gttttatcgg gcacacaggg tgagtagatg gccaacattg 25980atgcaggtca cgttccagta gagttgtgtg gcttcaccgc cggtgagcgg cttccactcg 26040ttgtggctga acacggtgcc atcggatgct atgaatgtgt tggggcgtag cttgtgaagc 26100tcggcttcca cgctctgccg gtaggcttcg gcgaggccct caaaatccat gtggtcgcag 26160gagagatttt cgaggcgtgt caggtcgaag ggtgtggggc agtcgtagct ggcgggggtg 26220tagagctggg tgaagtggtc ggcgatcttc tgcatgatta tttccttttc gttgctgata 26280acgttgttga gggtttatcg ggtggatgcg acaaggatgg cgtctacatc gatcacgtcg 26340atcatgtcgt ggagttcctc cgcttcgttc tcggcgagtg gctgccagtc gtagtcgccg 26400tacacggcgc cgtcaagggt gacagtccac agtggccgga tgagtcgtat ggcttcttgt 26460actttagcgt ggtacatgcg gcgcaccata tcgagatcga tgtcgtctga atggtttccg 26520gtgaggctgt ggaggctaag cgggtcgatt tctgtctgcc tgtagaggga tgtgaaggat 26580ggggtgatga gtgtgccatc catgggtgat gttcctttct ggattgtctt ggttgttgtg 26640gtttctagag tgtgtgggct gcgactcaca gtcaaggctg cgctcaatcc gaatgagcgt 26700ttcatgctgg agtgtcgggt gtgacagatg tcactgaagc ctttatggcc tctcccagcg 26760tctcaaatct tctaggggta ggattatgca gggttgacca tactagtcga ttctagggcc 26820attctagggc gtctgagggg tatatctggg tgatagcagg tgtggcagat gatctagcga 26880gtcaaggtgc cgagcttaga cataagatct atcatctagg tgtgtgagat gtatcacact 26940ctcctggctt ggtgtgcact ctcgaggcca ctctgccgat ctggcgtgga gggtgtagcc 27000cagaaatgcc gtttaaatcc ttcacgcgga gcctaggagc gccttgcagg gtgggggcta 27060ggtatttata cccccagcat attctgatcg attctatacg cccccagaag cctgatacac 27120gattcgctat ccaggcgcag atcatcagcc cctatcctgc ttagctaagc ctcaactatg 27180tggacagtgt tggatgctaa gagggaagaa ggatacggta aaagaaagaa gggggagtat 27240cagccttcac accggaggta cttaagttca ccttagagac ttagcactga gcattgagca 27300ctgagcagga tcagcccaga aaggggtaca cgccatcagg ggaggcttga gagtacgagg 27360agccctagcg acgagtactc gaaagcctga gggaataccc tcagcactga tgggcctagc 27420gtgttcggaa aggacacagg agtacagtgt gacagtcttt ccgggagcta aactccttcc 27480ggctagggca aacacccgtc ctaggctagc ccacaccctc atctgttaac cttccgttca 27540ttaaacgtta aggaaacttt taggtttgat ttttggacct ttactaccaa aaacacccgt 27600ttacacccct caaacccgcc tatagagcca aacgccggtg ttgagggtat ctctacctag 27660tgtgataggc tggacaggta gccagctgga cgcaaggccg aaatccgctg acgcggcttt 27720cacccttaca tccatcagtc taccaaacac tttaaagctt caaggcttag cgctaagccc 27780ttaaaacctt aacgcttagc accgagccct tgaggggctc ggcatcagtc ttaggtactt 27840taagtaactt taaaaccttc aaggcttagc ccttaaggat ctaagttact cttaaagctt 27900taaagtctta aaataaatat ataaccttaa tagttaaacg ttaaaagctt taaaccttaa 27960cacttaagtt aagtataaaa ccttaaaggc ttagcactta aggatataaa ctttacatca 28020gtgtttaaga ctttaaaact taaagtaatt attaaaactt aaaggtttat aagctttaag 28080cacttaaagt aactataaga ctttaaagac cttaagtact taaagttaac catcagtctt 28140aaactttaat attataccta taagtcttaa agcttatagg tataaaagtt ttagaagagc 28200taaggggtta acttctttac ttctctactc tctttggttc tttctctctt ctcttctttt 28260cttcatcagg ggagaagaga aaccttttac cgtcaacgct gatgggcttt tcgccgtgtg 28320actcgtgtgc ttctggtcgc aagctcccat cgcacactcc ccacactctt tcacccgtgt 28380cccctttcag gcttagcatg ttcggctgaa ggcgtacggc gtgtcacgcc aacaccctta 28440acaccaggta agacttaaag tacatattat atgtagaaga ctttaaaacc ttaagggtgt 28500tcccgcttgg cccgtgtcct ttaacgctag gcgctaagcc tgaaacgcga acacccatcc 28560acccccattt tgcttccgtg tccttctctt tttgacaccg ctggggggcg atgtgatctt 28620tctcacatgc caggggttag tggagaaaac aaacacccca ccacaaacag aacaccccct 28680caaacgaaca aaacagggcc tagaatcgaa tagaagggca ccggtagagt attcctaccc 28740ccaacacgtt ccaggctgtt acaggagcaa tgagaggctc acaggggcca taggagatca 28800gggggcgtga tggcacacac caaccgcaca gccagccaag cccaccggcg ctggcgggcg 28860cgactcatca cccaagcacg caagcaaggc caaaccgaat gcccactctg cggagcccag 28920atagcctggg acacacacga cctgccaacc agccccgaag ccgaccacat cacacccgtc 28980agccgcggag gactcaacac cctcgacaac gggcaaatca tctgcagaac atgcaacaga 29040agcaaaggca atcgcagcga accaaacatt agtttccaac aacaaaccac aaaaaccttg 29100atttcatggt gaaaaaaccc acaaacccca cgggaaccac cccctgcaca ccc 29153529109DNABacteriophage 1894 5tcccttttgt ggattgtctg tttgtcgact ttttgtgttg gtggtgagtg ttgtgcagcc 60tgagcttcct gggtctcgtg agtggtgtgg ggagacgcgt cagtggtggc gtgtgtgggg 120tgaggatagt cgcgcgcagt acgtgtctga tgaggagtgg ctgtttctca tggatgctgc 180ggtgattcat gattgtgtgt ggcgtgaggg tcgcgcggat ttggtggctt cgttgcgtgc 240tcatgtgaag gcttttatgg gcatgttgga tcgttattcg gttgatgtgg cgtctggtgg 300ccgtggtggg ggttctgcgg tggcgatgat tgaccggtat aggaagcgta aaggggccta 360atgtcgagtg ttgttggttc tcaggttcct cgtcaccggg tggctgcggc gtattcggtg 420tctgctggcg gtgatgctgg ggagttgggt cgtgcgtatg ggttgacgcc tgatccgtgg 480cagcagcagg tgttggatga ttggctggct gtcggtggta atggcaggct tgcttcgggt 540gtgtgtgggg tgtttgtgcc tcgccagaat ggcaagaatg cgatccttga ggttgtggag 600ttgtttaagg cgactattca gggtcgccgt attttgcata cggctcacga gttgaagtcg 660gctcgtaagg cgtttatgcg gttgaggtcg ttttttgaga atgagcggca gtttcctgac 720ttgtatcgta tggtgaaaac gatcagggcg acgaatggtc aggaggctat tgtgttgcat 780catccggatt gtgccacgtt tgagcgtaag tgtggttgtc cgggttgggg ttcggttgag 840tttgtggccc gttctcgggg ttctgctcgc gggtttacgg ttgatgattt ggtgtgtgat 900gaggctcagg agttgtcgga tgagcagttg gaggctttgc ttcctacggt gtctgcggct 960ccttcgggtg atccgcagca aatttttttg ggtacgccgc ctgggccgtt ggctgatggt 1020tctgtggtgt tgcgtttgcg tgggcaggct ttgtcgggtg gtaagaggat tgcgtggacg 1080gagttttcga ttcctgacga gtctgatccg gatgatgtgt cgcggcagtg gcggaggttg

1140gcgggtgaca ctaatccggc gttgggtcgc cgcctgaatt ttgggactgt cagcgatgag 1200catgagtcga tgtctgctgc cgggtttgct cgggagcggc ttggctggtg ggatcgtggc 1260cagtctgctg cgtctgtgat tccggcggat aagtgggctc agtcggctgt ggatgaggcg 1320agtttgtctg gcggtaaagt gtttggtgtc tcgttttctc gttctgggga tcgggttgct 1380ttggcgggtg ctggccggac tgatgctggt gttcatgttg aggttattga tgggctgtcg 1440ggaacgattg ttgatggtgt gggccggttg gcggactggt tggcggttcg ttggggtgat 1500actgaccgga ttatggttgc cgggtctggt gcggtgttgt tgcagaaggc gttgacggat 1560cgtggtattc cgggccgtgg cgtgattgtg gctgatactg gcacctatgt ggaggcgtgt 1620caggcgtttt tggagggtgt gcgttcgggt gttgtgtctc atccgcgtgc cgattctcgc 1680cgtgacatgt tggatattgc ggtgaggtcg gcggttcaga agaagaaagg ctctgcgtgg 1740ggttggggtt cctcgtttaa ggatggttct gaggtgcctt tggaggctgt gtcgttggcg 1800tttttggggg ctaaacgtgt tcgtcgtggc cgtcgggagc gtagtggtag gaagcgggtg 1860tctgtggtat gaactcggat gagttggctt tgattgaggg catgtacgat cgtatccaaa 1920ggttgtcttc gtggcattgt cgcattgagg gctactatga gggttctagc cgggtgcgtg 1980atttgggggt tgctattcct ccggagttgc agcgggtgca gacggtggtg tcgtggcctg 2040gtatagctgt ggatgctttg gaagagcgtc tggattggct tggctggact aatggtgacg 2100gctacggcct ggatggtgtg tatgctgcga atcggcttgc tacggcgtcg tgtgatgtgc 2160atttggatgc gctgattttt gggttgtcgt ttgtggctgt tatcccccag gatgatgggt 2220cggtgttggt tcgtccgcag tcaccaaaga attgcacagg caagttttcg gctgacgggt 2280ctcgtctgga tgctggcctt gtggtgcagc agacgtgtga tcctgaggtt gttgaggcgg 2340agttgttgct tcctgatgtg attgttcagg ttgagcggcg gggttcgcgt gaatgggttg 2400aggtggatcg tataccgaat gtgttgggtg ctgttccgct tgtgcctatt gtgaatcgtc 2460gccgtacttc taggattgat ggccgttcgg aaattacgag gtctattagg gcttacacgg 2520atgaggctgt gcgcacactg ttggggcagt ctgtgaatcg tgatttttat gcgtatcctc 2580agcgttgggt gactggcgtg agtgcggatg agttttcgca gcctggctgg gtcctgtcta 2640tggcttctgt gtgggctgtg gataaggatg atgatggtga cactccgaat gtggggtcgt 2700ttcctgtcaa ttcgcctaca ccgtattcgg atcagatgag actgttggcg cagttgactg 2760cgggtgaggc ggctgttccg gaacgctatt tcgggtttat cacgtctaac ccacctagtg 2820gggaggcttt ggctgccgag gaatctcggc ttgtgaagcg tgctgagcgg cgtcaaacgt 2880cgtttggtca gggctggctg tcggttggtt ttttggctgc caaggcgttg gattctcgtg 2940ttgatgaggc cgattttttt ggtgatgttg gtttgcgttg gcgtgatgct tcgacgccta 3000cccgggcggc tacggctgat gctgtgacga agcttgtggg tgccggtatt ttgcctgctg 3060attctcgtac ggtgttggag atgttggggc ttgatgatgt gcaggttgag gctgtgatgc 3120ggcatcgtgc tgagtcgtct gacccgttgg cggcactggc tggggctata tcgcgtcaaa 3180ctaacgaggt atgataggcg atggcttcgg gggttgaggc gaggcttgcg gcgactgagt 3240atcagcgtga ggcggtcagg tttgctggga agtatgcggg ctattattct gagcttggtc 3300gtttgtggcg tgccggcagg atgagtgaca cgcagtatgt tcgtttgtgt gtggagttgg 3360agcgtgccgg ccatgatggt tcggcatcgt tggctgccag gtttgtgtcg gattttcgcc 3420gattgaatgg tgtggatcct ggtttgatcg tgtatgacga gtttgatgct gcggcggctt 3480tggctaggtc tatttcgacc acgaagattc ttgagagcga cccggatagg gcgaatgaca 3540caattgatgc gatggcggcg ggttttgatc gggctgttat gaatgctggc cgcgacacgg 3600ttgagtggtc tgcgggtgcg cagggcaggt cgtggcgtcg ggttactgat ggtgatccgt 3660gtgctttttg tgccatgttg gctacgaggt cggattatac gaccaaagaa agggcgctca 3720ctactggaca tacgcggcgt cataagcgtg gcggtaagcg cccgtttggt tcgaaatatc 3780atgatcattg cgggtgtacg gtggttgagg ttgttggccc ttgggaacca aatagggctg 3840atgccgagta tcagaggacg tatgagaagg cccgtgagtg ggttgatgat cacgggttgc 3900agcagtcgcc tggcaatatt ttgaaggcta tgcgtactgt tggcggcatg agataatttg 3960ctgtggtttc cggttgtgcg ccgccggtta ttggtgcaca ttgttgtctc ccgcacgggg 4020gtcaacaatg ttgtgttgtt ttccgcaagg agtgtagggt taggctatgg ccgatcagag 4080tgttgaggaa cagaatgttg acaatgatgt tgtggagtcc ggaaaggata acggcattgt 4140tgatacagta aaagatgatg gcgggcagga ggtagccgac aatcagttga agaatgaagg 4200cgagggtaaa tcgccgggga ctgattggaa ggcggaggcc cgtaagtggg agtctcgtgc 4260taaaagtaat ttcgccgagt tggagaagct tcgtacatcg agtgaagatt ctggatctac 4320tattgatgag cttcgccgca agaatgagga actcgaagac aggatcaacg ggtttgttct 4380tgagggtgtg aagcgcgagg tggcttcaga gtatggtttg tccagtgatg cgatcgcttt 4440cttgtcgggt ggcgataagg agtcgcttgc cgagtctgcg aaagctttga agggtttgat 4500cgaccatagt agtggtggcg cgggtgtgcg ccgtcttgcg gggagtgccc ccgttgatga 4560tgttaaacga cgtgagggtg tcgcgtttgt ggatgctctt gtcaataatt ctaggagatg 4620atttgtgatg gctgacgatt ttctttctgc agggaagctt gagcttcctg gttctatgat 4680tggtgcggtt cgtgaccgtg ctatcgattc tggtgttttg gcgaagctct cgccggagca 4740gccgactatt tttggccctg ttaagggtgc cgtgtttagt ggtgttcctc gcgctaagat 4800tgttggtgag ggcgaggtta agccttccgc ttctgttgat gtttcggcgt ttactgcgca 4860gcctatcaag gttgtgactc agcagcgtgt ctcggatgag tttatgtggg ctgatgctga 4920ttaccgtctg ggtgttttgc aggatctgat ttccccggcg cttggtgctt cgattggtcg 4980cgccgtggat ctgattgctt tccatggtat tgatcctgcc actggtaaag cggctgccgc 5040tgtgcatact tcgctggata agacgaagca tattgttgat gccacggatt ctgctacgac 5100cgatctggtc aaggctgtcg gcctgattgc gggggctggt ttgcaggttc ctaacggggt 5160tgctttggat ccggcgttct cgtttgctct gtctactgag gtgtatccga aggggtctcc 5220gcttgccggt cagccgatgt atcctgctgc cgggtttgcc ggtttggata attggcgcgg 5280ccttaatgtt ggtgcttctt cgactgtttc gggtgccccg gagatgtcgc ctacctctgg 5340tgttaaggct attgttggtg atttctctcg tgttcattgg ggtttccagc gtaacttccc 5400gatcgagctg atcgagtatg gcgatccgga tcagactggt cgtgacctta agggccataa 5460tgaggttatg gttcgcgccg aggctgtcct gtatgtggct atcgagtcgc ttgattcgtt 5520tgctgttgtg aaggagaagg ctgcaccgaa gccgaatcct ccggccgaga actgattcat 5580ttgttgcggt gatatgtaca tgtgcagggg gtggtgttga tgggtatcat tttgaggcct 5640gaggatattg agcctttcgc cgatattcct cgagagaagc ttgaggcgat gattgccgat 5700gtggaggctg tggctgtcag tgtcgccccc tgtatcgcta aaccggattt caaatacaag 5760gatgccgcta aggctattct gcgcagggct ttgttgcgct ggaatgatac tggcgtgtcg 5820ggtcaggtgc agtatgagtc tgcgggtcct ttcgctcaga ctacacggtc taatactccc 5880acgaatttgt tgtggccttc tgagattgcc gcgttgaaga agttgtgtga gggtgatggt 5940ggggctggta aggcgttcac tattacaccg accatgagga gtagtgtgaa tcattctgag 6000gtgtgttcca cggtgtgggg tggcggctgt tcgtgcggtt ctgatattaa cggctgcgat 6060ggtcctttgt gggagatatg atatgactcg ttttccttat ggtgaaacgg ttgtgatgct 6120tcagccgact gttcgtgtcg atgatcttgg cgacaaggtg gaagactggt ctaagcctgt 6180cgagactgtg ttacataacg tggccatcta tgcttccgtt tcgcaggagg atgaggccgc 6240ggggcgtgac tctgactatg agcattggac actgcttttc aagcagcctg ttgaagctgc 6300cggttatcgt tgccggtggc gtatccgggg tgttgtgtgg gaggctgacg ggtctcctat 6360ggtgtggcat catccgatgt ctggctggga tgctggtacg caggttaatg tgaagcgcaa 6420gaagggctga tagattgtgg ctcaggatgt gaatgtgaag ctgaacttgc cgggtattcg 6480tgaggtgttg aagtcttctg gggtgcaggc tatgttggct gagcgtggcg agcgtgtcaa 6540gcgtgcggcc tcggcgaatg tgggcggtaa tgctttcgat aaggcccaat accgtaatgg 6600tttgtcgtcg gaggtgcagg ttcaccgtgt tgaggctgtc gctcgtatag gcaccacata 6660taagggtggg aagcgtattg aggcgaagca tggtacgttg gctcgttcga ttggggctgc 6720gtcgtgatcg tctacgatga ccccaggaag tgggctaaac gcgtgctcaa ggatgatggc 6780tggctgtctg atataccctg tgtggggacg gtgcccgatg attttacggg tgacctgatt 6840tggttggcgt tggatggtgg cccgcagttg catgtgcgtg agcgtgtttt tttgcgcgtg 6900aatgtgtttt ctgatacgcc tgatcgggct atgtctttgg cgcgtcgtgt tgaggctgtt 6960ctggctgacg gggttgatgg tgatccggtg gtgtactgta aacggtctac tggtcctgat 7020ttgctggttg atggtgcacg ttttgatgtg tattcgctgt tcgagctgat atgtaggcct 7080gcggagtctg agtaagctta ttgtttttgt tttaatgtaa ttgtttgata tttaatgggg 7140gttgtgatgg ctgcaacacg taaagcgtct aatgttcgct ctgctgttac gggtgacgtt 7200tatattggta aagctcatgc cggtgatact attgatggtg tgaaaacggt tcctgatggg 7260ctgactgctt taggatattt gtcggatgac gggtttaaga ttaagcctga gcgtaaaacg 7320gatgatttga aggcttggca gaatgcggat gttgttcgca cggttgctac cgagtcgtct 7380atcgagattt ctttccagtt gatcgagtct aagaaggagg ttattgagct gttttggcag 7440tcgaaggtta ctgctggatc cgattcgggt tcgttcgata tttctccggg tgccacgacg 7500ggtgttcacg ccctgttgat ggatattgtg gatggcgatc aggttattcg ctactatttc 7560cctgaggttg agttgatcga tcgtgacgag attaagggta agaatggcga agtgtacggg 7620tatggtgtga cgttgaaggc gtatcctgcc cagattaata ataagggtga tgcggtgtcg 7680ggtcgggggt ggatgacggc tttaaaagct gatactcctc cggttccgcc ttctccgaag 7740cctcagccgg atcctaatcc tccgtccgag aactgataca cgattttagg gattgttgat 7800agatgagtga cacaggttac acgttgaaga ttggtgaccg tagctgggtg ttggcggatg 7860cggaggagac ggctcaagct gtgcctgccc gcgtgtttcg ccgtgcagct aagattgccc 7920agtcggggga gtctgcggat ttcgcccagg ttgaggtgat gttttctatg ttggaggctg 7980ccgccccggc tgacgctgtg gaggccctgg aggggcttcc tatggttcgt gttgccgaga 8040ttttccgtca gtggatggaa tacaagcctg accagaaagc ggcctccttg ggggaatagt 8100ttggctccac ggcctgattg atgattatcg tggggccatc gaatatgatt ggaggacccg 8160gttcggttgc tcggtttatg atgttggtgg cccgcagatg tgttggggtg aggctgtccg 8220gctggctggc gtgttgtgta ccgatacgtc tagccagctg gcggcccacc tgaatggttg 8280gcagcgtccg tttgagtggt gcgagtgggc ggtgttggac atgctggatc attacaggtc 8340tgctaatagt gaggggcagc cggagcctgt ggcgaggccg acggatgagc gtagggcccg 8400gtttacgtct gggcaggtgg acgatatttt ggcgcgtgtt cgtgccggtg gcggggtgtc 8460tcgcgagatt aatattatgg ggtgaatagt gtatgtctgg tgagattgct tccgcatatg 8520tgtcgttgta tacgaagatg ccgggtttga aggcggatgt tggtaaacag ctttctgggg 8580tgatgcctgc ggagggtcag cgttcgggta gcttgtttgc taagggcatg aagttggcgc 8640ttggtggtgc cgcaatggtg ggtgccatca atgttgctaa gaagggcctc aagtctatct 8700atgatgtgac tattggtggc ggtattgctc gcgctatggc tattgatgag gcgcaggcta 8760aactgactgg tttgggtcat acgtcttctg acacgtcttc gattatgaat tcggctattg 8820aggctgtgac tggtacgtcg tatgcgttgg gtgatgcggc ttctactgcg gcggcgttgt 8880ctgcttcggg tgtgaagtct ggcgggcaga tgacggatgt gttgaagact gtcgccgatg 8940tgtcttatat ttcgggtaag tcgtttcagg atacgggcgc tatttttacg tctgtgatgg 9000ctcgcggtaa gttgcagggc gatgacatgt tgcagcttac tatggcgggt gttcctgtgc 9060tgtctttgct tgctaggcag acgggtaaaa cgtctgctga ggtgtcgcag atggtgtcga 9120aggggcagat tgattttgcc acgtttgcgg ctgcgatgaa gcttggcatg ggtggtgctg 9180cgcaggcgtc tggtcagacg tttgagggcg ctatgaagaa tgttaagggc gccctgggtt 9240atcttggtgc tacggctatg gcgccgtttc ttaacgggtt gcggcagatt tttgttgcgt 9300tgaatccggt tatcaagtcg gtgacggatt ctgtgaagcc gatgtttgct accgtcgatg 9360ctggtattca gcgtatgatg ccgtctattt tggcgtggat taaccgtatg ccggctatga 9420tcactcgaat gaatgcacag atgcgcgcca aagtggagca gttgaagggc atttttgcga 9480gaatgcattt acctgtccct aaagtgaatt tgggtgccat gtttgctggc ggcaccgcag 9540tgtttggtat tgttgctgcg ggtgtgggga agcttgttgc agggtttgcc ccgttggcgg 9600tgtcgttgaa gaatctactg ccgtcgtttg gtgctttgaa gggtgccgcc ggcgggcttg 9660gcggcgtgtt tcgcgccctg ggtggccctg ttggtattgt gatcggcttg tttgctgcca 9720tgtttgctac gaacgcccag ttccgtgccg ctgttatgca gcttgtggct gtggttggcc 9780aggcgttggg ccagattatg gccgctattc agccgctgtt tggtttggtt gctgggctgg 9840tggcccagtt ggcgccagtg tttgcccaga ttatcggtat ggttgccggt ttggctgccc 9900agttggtgcc tttgattagt atgcttgtcg cccggctagt tcctgtgatc acgcagacta 9960ttggtgcggt gacgcaggtt gctgccatgt tgttgcctgc gcttatgccg gttattcagg 10020ctgttgtggc tgtgatacgg caggttgttg gcgtgatcat gcagttggtg cctgttttga 10080tgcctgtgat tcaacagatt ttgggtgcgg tcatgtctgt gctgccgcct atcatcggcc 10140tgatccggtc gctgatacca gtcatcatgt cgattatgcg tgtggtgatg caggttgttg 10200gtgtcgtgct acaggtggtg gcccgcatta ttccggttgt gatgccaatt gtgacagctg 10260tgatcgggtt tgttgcacgt attcttggcg ctattgtgtc tgctgcagcc cgcattattg 10320ggactgtcac ccgtgtcatc tcatgggttg tgaatcattt agtgtctggc gtgaggtcta 10380tgggtacggc catcttgaat ggctggaatc atattagagc gtttacgtct gcgtttatta 10440acggtttcaa gtcggtgatt tctggcggcg tgaacgctgt tgtggggttt tttgcccggc 10500tgggttcttc ggttgcttct catgtgaggt ctggttttaa cgcggctcgt ggcgctgttt 10560cttctgcgat gaatgctatt cggagtgttg tgtcttcggt ggcgtctgct gttggcgggt 10620ttttcagttc gatggcgtct agggttcgta gtggtgctgt gcgcgggttt aatggtgccc 10680ggagtgcggc ttcttctgct atgcatgcta tgggttctgc ggtgtctagt ggtgtgcatg 10740gtgtgctggg ttttttccgg aatttgcctg gcaatattcg gcgtgcgctt ggtaatatgg 10800ggtccctgtt ggtgtctgct ggccgtgatg tggtgtctgg tttgggtaat ggtatccgga 10860atgctatgag tggcctgttg gatacggtgc gtaatatggg ttctcaggtt gcgaatgcgg 10920cgaagtcggt gttgggtatt cattccccgt cgagggtgtt tcgtgaccag gttggccggc 10980aggttgttgc cggtttggct gagggtatta ctggtaatgc tggtttggcg ttggatgcga 11040tgtctgatat ggcgggacgg ctgcctgatg cggttgatgc ccggtttggt gtgcgatcgt 11100ctgtgggctc gtttaccccg tatggcaggt atcagcgtgc gaatgataag agtgttgtgg 11160tgaatgtgaa tggacccacg tatggtgatc ctaacgagtt tgcgaagcgg attgagcggc 11220agcagcgtga cgctttgaat gcgttggctt acgcgtgatt gggggtgttg ttcatgtttc 11280ttcctgaccc gtctgatcgt tctggtttga ctgtgacgtg gttgatggat ccgctgtttg 11340gtggggagcg tgtgcttcat ttgacggatt atacgggtgc gtctcctgtc atgttgttga 11400atgattcgtt gcgcggtttg ggtgttcccg aggtggagca tttttctcaa actcatgttg 11460gggtgcacgg ctcggagtgg cgcgggttta atgtgaagcc tcgcgaggtg acgctgcctg 11520tgttggtgtc gggtgttgac ccggatccgg atggcgggtt tcgtgacggt tttttgaaag 11580cctatgacga gttgtggtct gcgtttcccc cgggggagga gggcgagttg tcggtgaaga 11640ctcctgccgg ccgtgagcgt gtgctaaaat gcaggtttga ttcggtggat gacacgttta 11700ctgttgatcc ggtgaatcgc ggctatgccc gctatgtgat tcatttgaca gcttatgacc 11760cgttttggta tggggatgag caaaagtttc gttttagtaa cgcgaagttg caggattggt 11820tgggtggcgg ccctgtcggc aaggatggta ccgcgtttcc tgtggtgttg acgcctggtg 11880ttggttcggg ttgggataat ctgtctaata agggtgatgt gcctgcgtgg cctgtgattc 11940gtgttgaggg cccgttagag tcgtggtctg tgcagattga tggtttgcgt gtgtcttcgg 12000attatcctgt cgaggagtat gattggatca ctattgatac ggatcctcgt aaacagtctg 12060cgttgttgaa tgggtttgag gatgtgatgg atcgtttgaa ggagtgggag tttgcgccta 12120tcccgcctgg cggttctaag agtgtgaata ttgagatggt gggtttgggt gccattgttg 12180tgtcggtgca gtacaggttt ttgagggctt ggtgaatagt tgatggctgg tcttgttccg 12240catgtaacat tgtttacgcc ggattatcgt cgtgtggcgc ctatcaattt ttttgagtcg 12300ttgaagttgt cgttgaagtg gaatggtttg tctacgctgg agttggtggt gtcgggggat 12360cattcaaggc ttgacgggtt gactaagccg ggtgcacggc tggttgttga ttatggtggt 12420ggccagattt tttctgggcc tgtgcgtaag gttcatggtg tgggtccttg gcgttcttcg 12480cgggtgacta tcacgtgtga ggatgatatt cgcctgttgt ggcgtatgct gatgtggcct 12540gtgaattatc gtcctggttt ggtcggtatg gagtggcgtg ccgacaggga ttatgcccac 12600tattcgggtg cggcggagtc ggttgctaag caggtgttgg gggataatgc ttggcgtttt 12660ccgcctggtt tgtttatgac cgatgatgag agtcgtggcc gctatattaa ggattttcag 12720gtgcggtttc acgtgtttgc cgataaattg ttgccggtgt tgtcgtgggc tcggatgact 12780gtcacggtga accagtttga gaatgcgaag tttgatcagc gtggtttagt gtttgattgc 12840gtgcctgctg tgacgcgtag tcacgtgttg actgccgagt ctggttcgat tgtgtcgtgg 12900gagtatgtgc gtgacgcccc gaaggcgaca tctgtggtgg ttggtggccg cggcgagggc 12960aaggatcggc tgttttgcga ggatgttgat tcgatggccg agggggattg gtttgatcgt 13020gtcgaggtgt ttaaggatgc ccgtaacacg gattctgagc atgtgcatct cattgatgag 13080gctgagcagg tgctgtccga gttaggggct acttcggggt ttaagatcga gttggctgag 13140tcggatgtgt tgcggtttgg gccaggcaat ctgatgccgg gtgatttgat ctatgtggat 13200gtgggttctg ggcctattgc ggaaattgtt cggcagattg atgtggagtg tgtatcgcct 13260ggtgatggtt ggacaaaggt gacaccggtt gcgggtgatt atgaggataa tccgtcggcc 13320ctgttggctc gccgtgttgc cggtttggct gcgggtgtgc gggatttgca aaagttttag 13380taagtgattg gggtttgttg tgggtattgt gtgtaaaggg tttgatggtg tgttgaccga 13440gtatgattgg gctcaaatgt ctggtctgat gggtaatatg ccgtctgtga aagggcagga 13500cgattttcgt gtcggcacta cggttcaggg tgccacagtg ttgtgtgagg tgttgcctgg 13560gcaggcttgg gctcacgggg tgatgtgcac gtcgaatagt gttgagacgg tgacggggca 13620gctgcctggt tctggcgaga cccgctacga ctatgtggtg ttgtctcggg attgggagca 13680gaacacagcc aggttggaga ttgttcctgg ggggcgtgcg gagcgtgccc gtgacgtgtt 13740aagggctgag cctggcgtgt ttcatcagca gttgttggct actttggtgg tgtcgtctaa 13800cgggttgcag cagcagttgg ataggcgtgc tatagcggcc cgtgtggcgt ttggggagtc 13860tgctgcgtgt gatcctaccc ctgtggaggg tgaccgggtg atggttcctt ctggtgctgt 13920gtgggctaat catgcgggcg agtggatgtt gttgtctccg cgtatcgaga cgggttctaa 13980gtcgatcatg tttggcggat ctgctgtgta tgcttacacg attccgtttg atcgccagtt 14040tagtagtccg cctgttgtgg tggcgtctat ggctacggcg gctgggggta cgcagcagat 14100cgatgtgaaa gcctacaata ttactaataa ggatttttat ttagcgttta ttacgaatga 14160tagttcgaag ccttctggtg tgcctgcggt ggctaactgg attgctgtcg gcgtgtaatg 14220tgcggcctgc aggtatgtga cgtgttgtgg tggttgtagt ggtagggggc tgtagtgtca 14280tggtttacac ctgcactggt ggcctctatc tgtaccgcgt tggccacggt tttgggttct 14340gttcaggcgg tcacgtctaa atctcggagg cgtttgcggc ggctgtcggc tcaggtggat 14400gcgatggaag agtatacgtg gggtgtgcgg cgcgaggtgc gaaggtttaa cgccgggctt 14460cctgatgatg tggagcctat gcatctccct gatgtgcccg agtttttgaa agatactgtt 14520gatggtggag gtgagtaggg ttgagggagt tggaggagga gaagcggcag cgccgcaatt 14580ttgagaaggc ttcactggtg ttgttgtttt tgtcgcttgt gttgttggcg gtggttgctg 14640cgggtgcttt gcgtttcggt gctgtatcct ctgagcggga ttcggagcag gctagggccc 14700agtcgaatgg tacagcggct cggggtttag ccagccgtgt gaagtgggtg tgtgcttcgg 14760gtggggtgga gtctgcgcgg cttcaccgtt ctggtttgtg tgtggatgct gtgcgtgttg 14820agcagcgtgt tcagggtgtg ccgggcccgg ctggtgagcg cggcccgcaa ggccctgcag 14880gtgctgacgg ccgggatggt gttaatggtt cggctgggct ggtgggccct gttggtccgc 14940agggctctcc cggtttgaat ggtgtgaaag gtcctgacgg gttgcctggc gcgaatggat 15000cggatggcca tgatggtgtt ccaggtcgtg caggtgctga cggtgtgaac ggggttgacg 15060gcgctgatgg tcgggatggt gttaatggtt cggctggtga gcgcggtgat gtgggccctt 15120caggtcctgc cggccctcaa ggtgcacagg gtgaacgggg tcctgctggc cctgttggtc 15180cgcagggttc tgccggtgcc gatggcacga atggtaaaga cggtaaggat gggcgctcgg 15240tggtgtctgt gtactgttcc gggggtcgcc tggttgtgaa atatggtgac ggtgtggctt 15300ctaccatatc gggttcggta gcctgcgaga gtgtgaaacc gtcacctata gtgactatat 15360catcccacaa atagaaagga gtggctgtga tggtagtgtt tggtggtgac atgttgtgag 15420gtttattcct gctgcgcatc actcggccgg ttcgaatagt ccggtgaacc gggttgtgat 15480tcatgcaaca tgcccggatg tggggtttcc gtccgcttcg cgtaaaggac gggcggtgtc 15540tacagcgaac tatttcgcgt ccccatcgtc gggcggttcg gcgcattacg tttgcgatat 15600tggggagacg gtgcagtgcc tgtcagaggg gactattggg tggcatgccc cgccgaatcc 15660gcatagtttg ggtatagaga tttgcgcgga tgggggttcg cacgcctcgt tccgtgtgcc 15720ggggcatgct tacacgaggg agcagtggct tgatcctcgc gtgtggcctg cggtggagcg 15780tgccgccatc ctgtgtagac gtttgtgtga caaatataat gttccaaaga ggaagcttag 15840tgcagccgat ttgaaggctg gcaggcgggg tgtgtgtggc catgtggatg ttacggatgc 15900atggcaccag tcggatcacg atgatccggg gccgtggttt ccgtgggaca ggtttatggc 15960cgtcgtgaac ggcggcagtg gagagagtga ggagttaacg gtggctgatg tacaagcgtt 16020acataatcag attaaacaat tgtctgccca gcttactggt tcggtgaata agctgcacca 16080tgatgttggt gtggtgcagg tgcagaatgg tgatttgggt aaacgtgtgg atgccctgtc 16140gtgggtgaag aacccggtga cggggaagct gtggcgtact aaggatgctt tgtggagtgt

16200ctggtattac gtgctggagt gtcgcagccg aatagacagg ctcgagtcta ctgttaacgg 16260tttgaaaaag tgatggtggt ttgttgtggg taaacagttt tggttgggcc tgctggagcg 16320tgccctgaaa acttttattc aaacgtttgt tgctgtgttg ggtgtgacgg cgggtgtcac 16380gtatactgcg gagtcgtttc gcggtttgcc gtgggagtct gccctgataa cagccacggt 16440tgctgcaata ctgtcgattg ctacatcgtt tggtaatccg tcgtttgtgg ccggcaagtc 16500gaaggtgacg cctgttgatg ctgggcttgt tccacccgcc gatacgggca tggttgagcc 16560gcacatggtt gatgtgttgg atcctggcat gatcgagccg atggatgatg ctgatcttgg 16620tggctatgtg ccgaggcgtg ccgccgagtc ggaggttggc acggtagagt ctactgttgc 16680ataattgaat atgtgtgtgc cccagcggtg ctgccacgat cgtgtggtgg ttgccgctgg 16740ggcacaattt ttgtgttcta cagtattcta tgattcgttg ttgtctatag tttcttcgag 16800catctgatac aggtggaggc aggcggagat agtatcgttg gcctggtcta gaacgttctg 16860gccgataaca tttttgtggt tgtcgcggtg gcagatgata gaccgcatga tatcgtcggc 16920cgccgattgc agtagtttgg tttggtatgc gattccggcg agccaatcta tggcttcctg 16980gcttgcccgt gtgtcgtctg gcatgccacg ggtgttgctg ttgtttgtgg ggtatcctgc 17040actgtcgcag taccacaaga tttcgctgca ctcgtctagc gtgtcctggt cgatagccag 17100atcgtcgagg ctgacttctt tgacggtaag gttcacgttg tcgagtgaga ttggtacacg 17160gtactggttt tcgacaccgc caacaatgtt ttctagctgt tgcatgttgg tgggctgttg 17220ttggatgatt cggtgtaccg ctgttttgag ggcagtgtag ggggtatttt gtgtgttgtt 17280catggtttta tcccatccct gtgctgtcgt cgttgccgtc tggatagtat ctactgtttg 17340cgtagcctgt tagggtgatg agtgtttggt ctgcccactg tttcactgtt tgtcttgtca 17400ccccgagtcg ttgggctgcc accgaatagg tttgatcata cccgtatact tccctgaatg 17460cggcaagccg tgctagccgt tttcgctgtt tggatggctg gcaggtgagg gtgtagtcgt 17520cgatggccag ttgtagatcg atcatggaga cgatgttgtt gccgtggtgt tgtggcgcgg 17580ttggtggggg tggcatgccc ggctctacac tcggtttcca tggtccgccg ttccagatcc 17640attgggcggc ttggatgatg tcggcggtgg tgtaggtttg gttcactggt caccccttga 17700acaggttgtc gaggttgtct gggttgctgg tgttagtggt gtcgaatcgt ccgacgcagt 17760ggcagtagtc gtacatgagt ttgataatgt gttggtggtc tcccaaatag gtgttgccgc 17820tgatgctgta ggtggctgtg ccgtctttac taataatgta ttttgcggtg atggtttcgg 17880gtgtttcggt gttggtgatg atggctgtgg tggtggcgcc tacggtttgt agcctggtgg 17940tttgggttcc gtcgtcgagg atggtagtaa ccatgagggt tgtcctttag atgctggttt 18000ggttgtcggc tagatgaata atatcggata aaggtttcgg ctggtctagg tgttgtatgg 18060ttttgttggc tagccgtttg gctaccctgt aacacatttt ggtatagtgt ttgttgtcta 18120ggttgtggta ttgttcccgc accgcaatat atagtaggga gtcttggtac aggtcgtctg 18180cactgattgc ggggtagtgt ccggctgttt tggtgcatgc ccggttgagt gtgcggagat 18240gatggcctgt ggcccatccc cacgatgcgg tggcggccag gtcggctttt gttggtcgtc 18300tactcatggc actatttcat ctcgctatct ggtagttgtt tggtgttttg ttgttgatag 18360tgtagcacac gagtccgggg tggccggtgg tgcctgtgcg gtgccggaac catgtggatt 18420cgccttccat ggatgggcat tggatgaagg tgcgttgtcc ttgctcggag atttcgaggt 18480ggtgccggtg cccggccatc agaatattag atacggtgcc gttgtggaat tcttggccgc 18540gccaccattc gtagtgttgg ttgttgcgcc attggtgtcc gtgggcgtgc aggatttgtg 18600tgccggccac attgacggtg gtggtcattt cgtccctgtc agggaagtgg aagtgtaggt 18660tggggtagtt gttggtgagc tggtaggctt ctgcgatggc gcggcagcag tccacgtcga 18720aggagtcgtc gtaggtggtg acgcctttac cgaatcttac ggcttcgccg tggttgccgg 18780ggatggatgt gactgtcaca ttttggcagt ggtcgaatat gtggactaac tggagcatgg 18840ccatgcgggt gagcctgatt tgttccgtca agggtgtttg ggtgcgccag gcgttgttgc 18900cgccttgtga cacgtatcct tcgatcatgt cgccaaggaa tgcgatgtgg actcgttgcg 18960gctgtcctgc ttgccaccag tagtgtttgg cggatgtgag ggagtgcaaa tagtcgtcgg 19020cgaagtgtgc tgtttctcct ccggggatgc ctttgccgat ttggaagtct cctgccccga 19080tgacgaaggc tgcagtgctg tagtcggtgt gggtgtcttg ttcgggtttt ggtggctgcc 19140attcggctag tttatcgacg agttcgtcta cagggtaggg gtcggttgta ggctggtggt 19200cgatgatttt ttgtatggat cggccggttt ctccgttcgg taaggtccat tcggagatgc 19260gtgtgcggcg cacggtgccg ttggctatgt tgtcgtcgat ggtgtcgatg gcgttgtcgt 19320ggttggctag ctgggtgagg agccggtcta tgttgtctat catcgggtat cctcctcttg 19380ttgctgggtg gtgttggctt gtttgcggcg atagtctttg atgacggtgg cggagatggg 19440gtatcctgcc tgggtgagtt gttttgctag ccatgaggcg gggatggttt tgtcggcgag 19500gacatctgcg gctttgttgc cgtagcgttg aatgagtgtt tcagttttgg ttgccatgat 19560gtcctagggg ttgtgtggtg ggctgccatc ctgtgcggca gtcgccgtcg tgtcctggtt 19620tgcgtgtgca ccacgatacg gttccgtctg tgtggttgag tgttttgccg cacatgatgt 19680cacgtaggtg ctcgggaaac ttatcgttgt tgttgtcccc gtgcgtgtcg atcaagtgtt 19740gggttttggc gaccatcatg tttcctatgt gtgaaagagt gtgcaaatac tatgcaggtg 19800tcatgggtgt ttatgcgggt atggttttca tcaccttgct gaacgtcacc tggttactgt 19860acatcatctg ggtgatttcc tgatccgttt tgtcggggtg ctgctttcgc aggttcgccc 19920actggcaggc gttgtcggtt tcctgctgta aacgtgtcag gtgctgctct gcgatgatgt 19980gtttccacat ggtccatgat atgtcgagcc gtttgagcat gtcgatggct ggcacgttga 20040acgagttgag gaagagtatt tcttcggtgt agtactgttt ttcgtattgg tcccatccgc 20100ttcggtgcct gttgggctgg tttttggggt aggcttcccg gcagattttg tgtaaccgtt 20160tggccatgtc gtcgggtagc ttgatgtcgg ggttggcgcg gatcatggat cgcatcccgt 20220cgtaggtggt gccccaggtg tgcatgatgt ggagtgggtc ttcaccatca gcccattttt 20280ctgcacagat ggcgaggcgg atgcgcctcc tggcggcctt agaggtgtcg ctgcggccgg 20340ggatggggca ggtgtcgagg ggatccatga tgctttagtg tacctttctt ggtttcgtgt 20400tgttgtctgg ttttattgta gcactgtgtt gagtgcttgt gtcaaccctg ttttgccggt 20460tttcaggtag gtgtctgtga catccccgac agtgaggggc acgtgggtgg cttgggggag 20520tgctacctgg agggtttggg ccatctggtc tcccgctttg tctgggtcgg accagatgta 20580gatgtggtcg tagccttcga agaatttggt ccagaaggtt tgccacgagg tggcgccggg 20640tagtgctacg gccgaccatc cgcattgttc gaggatcatg gagtcgaatt cgccttcgca 20700aatgtgcatt tcggctgccg ggtttgctag ggcggccatg ttgtagatgg agcctgtgtc 20760tcctgccggg gttaggtatt tggggtggtt gtgggttttg cagtcgtgcg ggagtgagca 20820gcggaaacgc atttttcgta tttctgctgg cccttcccat gtggggtaca tgtaggggat 20880ggtgatgcac tggttgtagt tttcgtggcc gggtatgggg tcattgtcga tgtatccaag 20940gtggtggtag cgggctgttt cttcgctgat gcctcttgct gagagcaggt cgagtatgtt 21000ttcgaggtgg gtttcgtaga gggctgaggc tttctggatt cggcggcgtt ccgcaatgtt 21060gtatgggcgt atgctgtcgt acattcgggt tttctttctc taatcgttgt tgtagcttgg 21120cgagtccgcc tccgacaccg catgtgtggc agtaccagac gcccttgtcg aggttgatgc 21180tcatggaggg ctggtggtcg tcgtggaacg ggcagaggat gtgttgctcg ttcctggacg 21240ggttgtaccg tatccggtag gtgtcgagga ggcggcaggt atcagaggtg tgggaggagc 21300tcgttgaggg ttgataccac ataggcttcg ctccatggct tgttgcgctg tttcatcact 21360acgagtccga tagtggactg gctttctcgg ttgcggtgtg tttcgtagtt gcgtgcctcc 21420cggctggctt gtttcacgaa ttgggctagg tgtggctggc cagctttcgc ctcgatcacg 21480tatgtgtggt ttttggtttt gaggatgagg tcgccttcgt cttcgcggcc gttgaggtgg 21540aggcgttcta tatcatgacc ggtgtcgcgt agctggtgga ggagtcgtgt ttcccattct 21600gcgcctgccc tgcggttgcg tgcctgttgt gttggcatga tagtcctttg tgtgttgggg 21660tcatgttcca tggctgtttt tcggcgaggg gtccgaagaa tgtgtattcg gggtaggctc 21720gtagccgttc gtattgggtg ccgtcggggc tggatttgcc tgtgcgctgt ttcaacactg 21780cgatgcgtgc ctctgccggg atcgataggc cgttgccgtt atcctcgcca ccatacaggg 21840agactccgag gatgagttgt ggtttttcgg agaggccgtt tttgatttct cgccgggcgg 21900gcgggtgttc gatgtcggag ccggttttgt cggttgcgtg gtgtgtgaca ataatggtgg 21960agtccgtgtc cctgcccaat gctgtgatcc attgcatggc ttcttgctgg gcctggtagt 22020cactctcgca gtcttgtatg tccatcaggt tgtcgataac aatgagtggt ggaaaggtgt 22080tccacatttc catgtaggct tgcagttcca tggtgatgtc tgtccatgtg atgggtgact 22140ggaatgagaa tgtgatgtgc gcgccgtggt ggatgctgtc tcgatagtat tctggcccgt 22200agtcgtcgat gttttgttgt atctgtgcgg tggtgtgttg ggtgttgagt gagatgattc 22260gtgtggaggc ctcccagggt gtcatgtccc ctgatatgta gagggcgggc tggttgagca 22320tcgctgtgat gaacatggct agcccggatt tttggctgcc ggagcgcccc gcaatcatga 22380cgagatcccc tttgtggatg tgcatgtcca ggttgcggta gaggggttct agttgtggta 22440tgcggggcag ctcggctgcg gtttgggagg ctctctcgaa ggatcgttgt agagagagca 22500tcggagcctt aatctatctg tttgttggat gtgtattggt ggtcagatgg agtcgatgtc 22560tacatcatca ctaccagtgg tgttgggctg gctgtctcgc cggtcaacgt aggctgctac 22620gaggtcgtag atggcgtcgt cgaggggttt gagcacgacc gcgttgaagc cgtttttggt 22680gcgcacggtg gctagtttga aggcctgctc ctcgccaagg tatgcttcta ggtcgcggat 22740catggagtgt gggcggtcgt tgttgccgcg tgctttctca ataatagcgt tggggatggt 22800ttctggggtg ccgttgttga gatcgtctag ggtgtggaag atggtgacat cagcgtagat 22860gcgatcggcg gtctgtccgc cgtagccttc ggtgttgtgc tggacgtcgt ggactttgaa 22920ggcgatggcg gtggcgtcct ggtttcggga ggggttgaag aaggtgctgt tgctgttgtt 22980gcggtagttg gcgagtccca ttgttgtttc ctttactgtt tgtgttgttt tgtttgtcgg 23040ttttatcggg tgaggctgtt tcgtttcgtg cggaaggctt cggatacgtc actgttactg 23100gtgatggtct ttttgtactg tttgagaagg tcggctagct gtgctttgct tgtggcattg 23160ttgattttgt cgatgatggt gttgtttcct tctgatgcga tgttgtctac gtagtctttg 23220gcggcctggt tgtatcggtc ttggaggatg atggatgctg tggcgatcag tgttgccagg 23280tcccagttcc ttgccgccga actgtttttg agtccgccta acaggtcgat gatagtcttc 23340ttcacctggt cggcggtgtc tcccctaatg acggtccatg gggcggcgta gtctccgccg 23400tatttgaggg tgacggtgaa tcggtcgtcg tctgtgttgt cggtcactgg tgctccttgc 23460cttcttctgt tggggctgtg atggtggttt ctatagggta cctgtaggcg tctttcccgt 23520ctacagccca acaggcgtcc ttgacggggc atcctttaca gagtgctgtg acgtggggta 23580cgaagatgcc ttcgctgatt cctttcattg cttgactata catggatgat acatgccggt 23640aggtgttgtt gtcaaggtcg tacagttcgg tggatgtgcc ttgtgtcggg gacttgtcgt 23700cgttgcggct ggtggctggc gtccaaaaca tgcctttcgt gacatggatg tcgtgttggt 23760tgagcatgta ccggtaggtg tgcagctgca tgctgtcggc gggtaggcgt ccggttttga 23820ggtcgaggat gaaggtttcg ccggtgtcgg tgttggtgaa gattcggtcg atgtagccga 23880cgatctgggc gccgtcgggg agggtggttt ctaccgggta ttcgatgcct ggctggccgt 23940ccagaattgc ggtgatgtat tctgggtggt tgcgcctcca gtttttccac cggtccacaa 24000aggtggggcc gtaaaccatc caccaattgt agtctttttt gtgtggcccg cctgactcgc 24060acatgttttt gcatattctg ccggagggtt tgatttctgt gccttcggat tcggcgaggg 24120cgatttgggt gtcgaaaatg tttttgaagg atgagagttt gtcgggcagt gcagggtatt 24180cggcgggatt gtacaggtgt aggtcgtatt gttcggtgat gtggtgtatg gcgcttccgg 24240cgatggtggc ataccaggtg tggtgttggg catggtagcc gtgttggagg cgccattttt 24300ctccgcattc ggcccactgg gtgagtgaac tgtaggagat gtggcctgga tggttgatgg 24360ttttcgggta ttgtgctagg ggcattactt gtcgcttttg ttccatgggt tgcgggtgtc 24420ttggccggcg tggtgttgct ggtatgcgag gagtgcgagg cagtgccagg cggcgtgtgc 24480cagatgcggc aaatgtgatt cgtggtcgag gttgttgcct tgctgccatg atagtaggtg 24540cctgtagagg gcgtcgacac tgtggctcca cgggtatcct ccggtccagt tgttgtcgcc 24600gtatttggtg gcgccgtagc ctgctacttc gcctagggcg tgaagggatg ctgggtcgat 24660gagggatagc ctgcattgtt tgagttcttt tcgggcaccg ctgttcgggt cggtgtacat 24720gcgggtgggc tcatccatgg ggtgtgtgct ccttaagggt gggttactgg ttgttatcgt 24780gggctagggc gacggcgaga ataatgatgg cgagggtttc tgcgatcagt atgggtgttg 24840tgatcattta gtgtctcggg gattgttggt gagggttgag gcgcctagga gggtggcgag 24900ggcgcatgcg gcgatgatgg cgagggctgc cttgtgtggg gtgccggtgg cgtacatcca 24960tgtgatgatg ccgccttgga tccaggctag gctggtgaag aacgtttcgt aactgtgcag 25020ctcaatgttg ttgttgggtg tgttcatgct tgctcctgaa gaatggtgtt gatggtttta 25080taaatgttgt acaggtcggt ttcgatagat aacagttggt tgatttggtg gtcgagatca 25140atgtctgggt tgagggtgtt gatgcgggag gcgatatcgg tggctgtgcg tagtgtgccg 25200ccggtgtggt gaatgatgtg tgccgtgtcg gctagtccgg tggtgacggc gtagtgggag 25260aggagaggca tagcagggat gctccttgac gggttactgt tgcgggttga tgttgaggtc 25320ggtgacgtgc gggtggtctt ctgttccggt gacgaggcag tggacggtga ctgggagttt 25380ggatgcgccg ggctgtttca tggttgcacc gtagacgatg gagaaggtgt ctttaccgat 25440ggttttgtgg agttggaggt cgatgtcggg gttgccgttc cagttgacac cgtgtgcggc 25500ggcctgttgt tcggctttgc ggttgcaggt gtgtgccgcg gtgatcatgg tgagtccggt 25560ggcggtttct tcaccccgtg tttgggcttg cttgtgggtt ttggtctgct cggcttgtag 25620ggagcgggtg gcggctgcct gacgtgccgc tttctcggct ttgcgctgtt ggacggtttt 25680gggggtccat tcggtgttgg ctgttgtggc ctgtggggct ggctgtgagg cgagtggcgg 25740attgtcgtct ggggctggca tgaaggaggc tgcggcgatg atggcggctg tgatgcctgc 25800gatggtgtag cctttcttct tgttcatggc tgttgtcccc tttccggggt gttgttcgtt 25860gctgacatga tcaatacttc cagtgactgg accgcgtgtc aaggctgcgc tcaacgattg 25920tgagcgatcc ttgtgtggct aggggtttta tcgggcacac agggtgagta gatggccaac 25980attgatgcgg ctcacattcc agtagagttg tgtggcttca ccgccggtga gcggcttcca 26040ctcgtcgtgg ctgaacacgg tgccatcggt ggcgatgaat gtgtttgggc gtagtttgtg 26100aagttcggct tccacgctct gccggtaggc ttcggcgagg ccttcaaaat ccatgtggtc 26160gcagtggagg ttttcgaggc gtgtcaggtc gaagggtgtg gggcagtcgt agctggtggg 26220ggtgtagagc tgggtgaagt ggttggcgat cttttgcatc atgattcctt ttctggtgat 26280ggtgtgttga ggatttatcg ggtggatgcg acaaggatgg cgtctatgtc gatcatgtcg 26340atgagatcgt ggagttcctc ggcttcattc tcggtgagcg gctgccagtc gtagtccccg 26400tatagggcgc cgtcgagggt gacagtccac agtggccgga tgagtcgtat ggcttcttgt 26460actttagcgt ggtacatgcg gcgcaccata tcgagatcga tgtcgtctga atggtttccg 26520gtgaggctgt ggaggctgag cgggtctatt tctgtctgcc tgtagaggga tgtgaaggat 26580ggggtgatga gtgtgccatc catgggtgat gttcctttct ggattgtctt ggttggttgt 26640tgtggttttt atggtgtgag ggttgtgatc catagtcaag gctgcgctca ttcggtttga 26700gcgtttcata tgggtgtggc atggggtgtg gcgtatctca cttaagcctt tatggcctct 26760ctcggcgtct caaatcttct aggggtagga ttatataggg ttgaccctgc tgatcgattc 26820tagggccctt ctagggcgtc tcagaggtat gtctgagtga tagcaggtcc ggtagatgac 26880ccggcagatc tgccttggct ttcatcgcgg gggtcgaggt gccagatctg ggcatggaat 26940ctacaccctc ataccgtgtg agataggcca cactcgcctc gtatggtgtg cacccccaag 27000gccactctgc caatctggcg tggagggtgt agcccagaaa tgccgtttaa agcctcaggg 27060atacgcctag gagcgccttg cggggtgggg gctaggtatt tataccccca gcacattctg 27120atcgattcta gacgccccac agagcctgat acacgatcaa ccatcccagc atagatcacc 27180agcccctatc ctgcttagct aagcctcaac tatgtggaca gtgtgggata ctgtggggga 27240agaaggacac ggtaaaaaga aggggggcat cagccttcac acctgaggta cttaagttaa 27300ccttagggtc ttagcgctga gcatttagca ccgagcccct caagggctcg gcataagccc 27360gagcaggctc agccgatcag gcacagccct gaaaggggta cacgccatca gggaaggctt 27420gagagtacga ggagccttag cgacgagtac tcgaaagcct gagggaacac cctcagcact 27480gatgggccta gcgtgttcgg aaaggacaca agagtacagt gtgacagctg tccgggagtg 27540aaacccgttc tgactagggg tttcagcctt aacaaccctc aaaggttaca agactctaag 27600aaaatttaag gaaaagttta ggtttaattt ttggaccttc actaccaaaa acacccgttt 27660acacccatca aacccgccta tagagccaaa tccaccagtt tgactcatcc caggtggggt 27720atgataggct ggacaggtag ccagctggac gcaaggccga aatccgctga cgcggctttc 27780acccttacat ccatcagtct accaaacact ttaaagcttc aagggcttag cgctaagcac 27840cgagcccctc aagggctcgg catcagtctt aaagccttaa acacttaaag tacatataaa 27900accttaacag ttaaacgtta aaagctttaa accttaacac ctaagttaag tataaaacct 27960taaaggctta gcacttaagg atataaactt aacatcagtg tttaagactt taaaacttaa 28020aataactatt aagactttaa aaaccttaag tacttaaagt taaccatcag tcttaaactt 28080taatattata acctataagt cttaaagctt ataggtatta tattataata taagtattaa 28140agcttataag ttataaaagt tttagaagag ctaagaggtt aacttcttta cttctctact 28200ctctttggta ctttctctct tctcttcttt tcttcatcag gggagaagag gaacctttta 28260ccgtgtgact cgtgtgcttc tggtcgcaag ttcccatcgc acactcccca cactctgaca 28320cccgtgtccc tttacggctt ggcgtgttcg gctgaaggcg tacggcgtgt cacgctcaca 28380cccttaacac cagatgagac ttaaagtgta tattatatgt agaagacttt aaaaacctat 28440aaggtgttcc tgctgagcct gtgtccttta acgctaggcg ccaagcgcta agctgtgaaa 28500cgcgaacaca cacccacccc catttttctt ccgtgtcctt ctcttttgac acaaccgggg 28560ggcgatgtga tctttttcac atgccggggg gtatgagtag aaaacaaaca ccccggcaca 28620aacagaacac cccctcaaac aaacaaaaca gggcctagaa tcgatcggca gggcaagggt 28680agagtattta tacccctaga cgatcccaag cccttataga ggcaaataag acccgtacag 28740ggctaggcga ggaacagaca catcatggca cgcaccaacc gcacagccag ccaagcccac 28800cggcgctggc gggcaagact catcacccaa gcccgacaac aaggccaaac cgaatgccca 28860ctctgcggag cccagatcgc ctggggcaca cacgatctac caaccagccc cgaagccgac 28920cacatcacac ccgtcagccg cgggggactc aacaccctcg acaacgggca aatcatctgc 28980agaacatgca acagaagcaa aggcaacaga acacaaccaa acatcaaatt ccaacaacaa 29040accacaaaaa ccttgattcc atggtgaaaa acccgccaac ccccaccggg cacaccccct 29100gcacacccg 291096855DNABacteriophage 103609 6gtgagataca ttcctgcggc gcatcattct gccggctcga atagtccggt gaatagggtt 60gtgattcatg cgacgtgccc ggatgtgggg tttccgtctg cctcgcgtaa agggcgggcg 120gtgtctacag caaactattt cgcgtcccca tcgtcgggtg gttcggcgca ttatgtttgc 180gatattagtg agactgtgca gtgcttgtcg gagtctacga ttgggtggca tgccccgccg 240aatccgcata gtttgggtat cgagatttgc gcggatgggg gttcgcacgc ctcgttccgg 300gtgccggggc atgcttacac tcgggagcag tggcttgatc ctagggtgtg gcctgcggtg 360gagaaggctg ccatcctgtg tagacgtttg tgtgacaaat ataatgttcc gaagaggaag 420cttagtgcag ccgatttgaa ggctggtagg cggggtgtgt gcggccatgt ggatgtgacg 480gatgcgtggc atcagtcgga tcatgacgat ccggggccgt ggtttccgtg ggacaggttt 540atggccgttg tcaacggcaa agatgagagt ggggagttaa ctgtggctga tgtgaaagcc 600ttgcatgatc agattaaaca attgtctgct cagcttactg gttcggtgaa taagctgcac 660catgatgttg gtgtggttca ggttcagaat ggtgatttgg gtaagcgtgt tgacgccttg 720tcgtgggtga agaatccggt gacggggaag ctgtggcgca caaaggatgc tttgtggagt 780gtctggtatt acgtgctgga gtgtcgtagc cgtattgaca ggcttgagtc gactgtcaac 840ggtttgaaaa agtga 8557864DNABateriophage 103672 7gtgaggttta ttcctgctgc gcatcattct gccggctcga atagtccggt gaatagggtt 60gtgattcatg cgacatgccc ggatgtgggg tttccgtccg cttcccgtaa ggggcgggcg 120gtgtctacgg cgaactattt cgcgtcccca tcggcgggcg gttctgccca ttatgtgtgc 180gatatttcgg agacggtgca gtgcttgtcg gagtctacga ttgggtggca tgccccgccg 240aatccgcata gtttgggtat cgagatttgc gcggatgggg gttcgcacgc ctcgttccgt 300gtgccagggc atgcttacac gagggagcag tggctggatc ctagggtgtg gcctgcggtg 360gagaaggctg ccatcctgtg tagacgtttg tgtgacaaat ataatgttcc gaaaaggaag 420cttagtgcag ccgatttgaa ggctggcagg cggggtgttt gcgggcatgt ggatgttacg 480gatgcgtggc atcagtcgga tcatgacgat cctgggccgt ggtttccgtg ggacaaattt 540atggctgtgg tgaatggcca cggcggcggt tcaagtagtg aggagttaac ggtggctgat 600gtgaaagcgt tacataatca gattaaacaa ttgtctgctc agcttactgg ttcggtgaat 660aagctgcatc acgatgttgg tgtggttcag gtgcagaatg gtgacctggc gcgccgtgtt 720gatgccttgt cgtgggtgaa gaatccggtg acggggaagc tgtggcgcac taaggatgcc 780ctgtggagtg tctggtatta cgtgctggag tgtcgtagcc gtattgacag gcttgagtct 840gctgttaacg gtttgaaaaa gtga 8648858DNABacteriophage 1894 8gtgaggttta ttcctgctgc gcatcactcg gccggttcga atagtccggt gaaccgggtt 60gtgattcatg caacatgccc ggatgtgggg tttccgtccg cttcgcgtaa aggacgggcg 120gtgtctacag cgaactattt cgcgtcccca tcgtcgggcg gttcggcgca ttacgtttgc 180gatattgggg agacggtgca gtgcctgtca gaggggacta

ttgggtggca tgccccgccg 240aatccgcata gtttgggtat agagatttgc gcggatgggg gttcgcacgc ctcgttccgt 300gtgccggggc atgcttacac gagggagcag tggcttgatc ctcgcgtgtg gcctgcggtg 360gagcgtgccg ccatcctgtg tagacgtttg tgtgacaaat ataatgttcc aaagaggaag 420cttagtgcag ccgatttgaa ggctggcagg cggggtgtgt gtggccatgt ggatgttacg 480gatgcatggc accagtcgga tcacgatgat ccggggccgt ggtttccgtg ggacaggttt 540atggccgtcg tgaacggcgg cagtggagag agtgaggagt taacggtggc tgatgtacaa 600gcgttacata atcagattaa acaattgtct gcccagctta ctggttcggt gaataagctg 660caccatgatg ttggtgtggt gcaggtgcag aatggtgatt tgggtaaacg tgtggatgcc 720ctgtcgtggg tgaagaaccc ggtgacgggg aagctgtggc gtactaagga tgctttgtgg 780agtgtctggt attacgtgct ggagtgtcgc agccgaatag acaggctcga gtctactgtt 840aacggtttga aaaagtga 858940DNABacteriophage PA6 9cttgtttgat ggttttgtag tagccgacga ggatgcgctg 401026DNABacteriophage PA6 10agtattgtgc cgccacggcg tagcgg 261157DNABacteriophage PA6 11gaaggcgtcc cagcagtatt caataatgtg ttgtagtaca ctatcgggca tgtctcg 571276DNABacteriophage PA6 12ttcgtcgagc cacgcgtcga caatgatgtt gcgtatggcg cgtttgtctt tggtggtggg 60tttgaatgcg atgctc 7613379DNABacteriophage PA6 13gatggcttct ttcgcccaat aggatgtgcc accgctggtc cagtatccga gtttgttgcg 60ctgcatgccc ttggcgtcca tctcgtcgat agtgaggcac ctgcggcgat tggggcctgt 120cttgaccccg tggtcgcctg tccggtgcat gtcgcctgag gtggtactcg tgaatgtttc 180atggcagatg gtacagtgct ctggtcgata tccggtgatt gtgctatcgc acttgtggca 240tgtccattcc atgattgctc ctattttcca ttataagact tcctgtagtg ccattttagc 300gccttgcggg tcttgggggt acaactatat aggtcaggtg tttctaggcg attctaggct 360cattgtgtgt ggctggggt 379

Claims

1. A bacteriophage capable of lysing a P. acnes bacterium and incapable of lysing any bacterium which is not P. acnes, and which is incapable of sustaining lysogeny in a bacterium.

2. A bacteriophage according to claim 1 which lacks the ability to express at least one gene necessary for sustaining lysogeny.

3. A bacteriophage according to claim 2 having a genome which lacks all or part of at least one gene necessary for sustaining lysogeny.

4. A bacteriophage according to claim 1 having a genome which comprises defects in non-coding regions which affect the ability of the phage to sustain lysogeny.

5. An isolated bacteriophage according to claim 1 which is naturally occurring.

6. A bacteriophage according to claim 1 capable of lysing a plurality of strains of the P. acnes bacterium.

7. A bacteriophage according to claim 1 capable of lysing at least 5 strains of the P. acnes bacterium.

8. A bacteriophage according to claim 1 which is isolated and selected from: 103609 (Accession no. NCIMB 41350); 103672 (Accession no. NCIMB 41351); and 1894 (Accession no. NCIMB 41349).

9. A bacteriophage according to claim 1 having a genome having sequence identity of at least 88% with the genome of the bacteriophage deposited under Accession No. NCIMB 41349.

10. A bacteriophage according to claim 1 having a genome which comprises the DNA sequence of SEQ ID NO: 5, a genome having at least 88% sequence identity with the DNA sequence of SEQ ID NO:5, or a genome which comprises a functional fragment of the DNA sequence of SEQ ID NO: 5.

11. A bacteriophage according to claim 10 wherein the functional fragment is selected from within the Open Reading Frames shown in FIG. 4.

12. A bacteriophage according to claim 10 wherein the functional fragment comprises a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:8.

13. A bacteriophage according to claim 10 wherein the functional fragment comprises the DNA sequence of SEQ ID NO:8.

14. An isolated bacteriophage according to claim 1 which is 1894.

15. A bacteriophage according to claim 1 having a genome having sequence identity of at least 87% with the genome of the bacteriophage deposited under Accession No. NCIMB 41350.

16. A bacteriophage according to claim 1 having a genome which comprises the DNA sequence of SEQ ID NO: 3, a genome having at least 87% sequence identity with the DNA sequence of SEQ ID NO:3, or a genome which comprises a functional fragment of the DNA sequence of SEQ ID NO: 3.

17. A bacteriophage according to claim 16 wherein the functional fragment is selected from within the Open Reading Frames shown in FIG. 2.

18. A bacteriophage according to claim 16 wherein the functional fragment comprises a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:6.

19. A bacteriophage according to claim 16 wherein the functional fragment comprises the DNA sequence of SEQ ID NO:6.

20. A bacteriophage according to claim 1 which is 103609.

21. A bacteriophage according to claim 1 having a genome having sequence identity of at least 88% with the genome of the bacteriophage deposited under Accession No. NCIMB 41351.

22. A bacteriophage according to claim 1 having a genome which comprises the DNA sequence of SEQ ID NO: 4, a genome having at least 88% sequence identity with the DNA sequence of SEQ ID NO:4, or a genome which comprises a functional fragment of the DNA sequence of SEQ ID NO: 4.

23. A bacteriophage according to claim 22 wherein the functional fragment is selected from the Open Reading Frames shown in FIG. 3.

24. A bacteriophage according to claim 22 wherein the functional fragment comprises a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:7.

25. A bacteriophage according to claim 22 wherein the functional fragment comprises the DNA sequence of SEQ ID NO:7.

26. A bacteriophage according to claim 1 which is 103672.

27. A bacteriophage according to claim 1 having a genome which does not comprise the DNA sequence of SEQ ID NO:9.

28. A bacteriophage according to claim 1 having a genome which does not comprise the DNA sequence of SEQ ID NO:10.

29. A bacteriophage according to claim 1 having a genome which does not comprise the DNA sequence of SEQ ID NO:11.

30. A bacteriophage according to claim 1 having a genome which does not comprise the DNA sequence of SEQ ID NO:12.

31. A bacteriophage according to claim 1 having a genome which does not comprise the DNA sequence of SEQ ID NO:13.

32. A bacteriophage according to claim 1 modified to comprise a marker molecule.

33. An isolated polynucleotide having the nucleotide sequence of the genome of a bacteriophage according to claim 1.

34. An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:3 or of a functional fragment of the DNA sequence of SEQ ID NO:3, wherein a bacteriophage comprising the polynucleotide is a bacteriophage according to claim 1.

35. An isolated polynucleotide having sequence identity of at least 87% with the DNA sequence of SEQ ID NO:3, wherein a bacteriophage comprising the polynucleotide is a bacteriophage according to claim 1.

36. An isolated polynucleotide according to claim 34 wherein the functional fragment is selected from within the Open Reading Frames shown in FIG. 2.

37. An isolated polynucleotide according to claim 34 wherein the functional fragment comprises a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:6.

38. An isolated polynucleotide according to claim 36 wherein the functional fragment comprises the DNA sequence of SEQ ID NO:6.

39. An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:4 or of a functional fragment of the DNA sequence of SEQ ID NO:4, wherein a bacteriophage comprising the polynucleotide is a bacteriophage according to claim 1.

40. An isolated polynucleotide having sequence identity of at least 88% with the DNA sequence of SEQ ID NO:4, wherein a bacteriophage comprising the polynucleotide is a bacteriophage according to claim 1.

41. An isolated polynucleotide according to claim 39 wherein the functional fragment is selected from within the Open Reading Frames shown in FIG.

42. An isolated polynucleotide according to claim 39 wherein the functional fragment comprises a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:7.

43. An isolated polynucleotide according to claim 41 wherein the functional fragment comprises the DNA sequence of SEQ ID NO:7.

44. An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:5 or of a functional fragment of the DNA sequence of SEQ ID NO:5, wherein a bacteriophage comprising the polynucleotide is a bacteriophage according to claim 1.

45. An isolated polynucleotide having sequence identity of at least 88% with the DNA sequence of SEQ ID NO:5, wherein a bacteriophage comprising the polynucleotide is a bacteriophage according to claim 1.

46. An isolated polynucleotide according to claim 44 wherein the functional fragment is selected from within the Open Reading Frames shown in FIG. 4.

47. An isolated polynucleotide according to claim 44 wherein the functional fragment comprises a DNA sequence having sequence identity of at least 95% with the DNA sequence of SEQ ID NO:8.

48. An isolated polynucleotide according to claim 46 wherein the functional fragment comprises the DNA sequence of SEQ ID NO:8.

49. An isolated polynucleotide according to claim 33 having a nucleic acid sequence which does not comprise that of SEQ ID NO:9.

50. An isolated polynucleotide according to claim 33 having a nucleic acid sequence which does not comprise that of SEQ ID NO:10.

51. An isolated polynucleotide according to claim 33 having a nucleic acid sequence which does not comprise that of SEQ ID NO:11.

52. An isolated polynucleotide according to claim 33 having a nucleic acid sequence which does not comprise that of SEQ ID NO:12.

53. An isolated polynucleotide according to claim 33 having a nucleic acid sequence which does not comprise that of SEQ ID NO:13.

54. An isolated polynucleotide having a nucleic acid sequence which is complementary to that of the polynucleotide defined in claim 33.

55. An isolated polynucleotide comprising the polynucleotide according to claim 33 and a nucleic acid sequence encoding a marker molecule.

56. An isolated polypeptide having an amino acid sequence encoded by the polynucleotide according to claim 33.

57. A composition comprising at least one bacteriophage according to claim 1 and an adjuvant, carrier or vehicle.

58. A composition according to claim 57 comprising two or more different bacteriophage.

59. A composition according to claim 58 wherein each of the two or more bacteriophage is a bacteriophage as defined above.

60. A composition comprising an isolated polynucleotide according to claim 33 and/or an isolated polypeptide as defined above and an adjuvant, carrier or vehicle.

61. A composition according to claim 57 in a form suitable for oral, intravenous or topical administration.

62. A composition according to claim 57 which further comprises at least one further agent selected from antibiotics, anti-comedonals, anti-P. acnes agents, anti-inflammatories and anti-seborrhoeics.

63. A composition according to claim 57 for use in the prevention or treatment of acne and wherein each at least one bacteriophage is present in an effective amount.

64. A composition according to claim 57 for use in the prevention or treatment of acne and wherein the isolated polynucleotide and/or the isolated polypeptide is present in an effective amount.

65. A method of preventing or treating acne comprising administering an effective amount of at least one bacteriophage according to claim 1 to an individual in need of such prevention or treatment.

66. A method of preventing or treating acne comprising administering an effective amount of an isolated polynucleotide according to claim 33 and/or an isolated polypeptide as defined above and/or of a composition as defined above to an individual in need of such prevention or treatment.

67. A method of improving the appearance of an individual comprising administering to the individual an effective amount of at least one bacteriophage according to claim 1.

68. A method of improving the appearance of an individual comprising administering to the individual an effective amount of an isolated polynucleotide according to claim 33 and/or an isolated polypeptide as defined above and/or of a composition as defined above.

69. A method for isolating a bacteriophage capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes and is incapable of sustaining lysogeny in a bacterium, comprising:a) obtaining a sample of bacteria from a skin surface:b) isolating from the sample bacteriophage which lyse propionibacteria;c) testing the bacteriophage to determine if it is capable of lysing at least one P. acnes strain;d) testing the bacteriophage to determine if it is capable of lysing non-P. acnes bacterial strains;e) testing the bacteriophage to determine whether it is capable of sustaining lysogeny in a P. acnes strain;f) isolating a bacteriophage which has been shown in steps (c), (d) and (e) to be capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes, and incapable of sustaining lysogeny in a bacterium.

70. A method for identifying a bacteriophage which is capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium, comprising:a) exposing a P. acnes bacterium to the bacteriophage and determining that the bacterium is lysed;b) exposing at least three different species of bacteria which are not P. acnes bacteria to the bacteriophage and determining that the bacteria are not lysed;c) determining that the bacteriophage is not capable of sustaining lysogeny in a bacteria.

71. A bacteriophage isolated using the method according to claim 69 or identified using the method as defined above.

72. A bacteriophage obtainable using the method according to claim 69 or identifiable using a method as defined above.

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