Patent application title: PROBIOTIC COMPOSITIONS COMPRISING LACTOBACILLUS REUTERI STRAINS AND METHODS OF USE
Inventors:
IPC8 Class:
USPC Class:
1 1
Class name:
Publication date: 2022-03-24
Patent application number: 20220088094
Abstract:
The present invention relates to probiotic compositions and methods for
increasing animal health. The probiotic compositions include one or more
isolated strains of novel Lactobacillus reuteri strains which colonizes
the gastrointestinal tract to increase the health of an animal.Claims:
1.-45. (canceled)
46. A probiotic composition for increasing animal health comprising an isolated first Lactobacillus reuteri strain 3632 (ATCC PTA-126788) and an isolated second Lactobacillus reuteri strain 3630 (ATCC PTA-126787).
47. The composition of claim 46, wherein the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain are present at a ratio of 0.75-1.5:1.
48. The composition of claim 46, wherein the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain are included in an amount of 10.sup.2-10.sup.8 CFU/kg of the composition.
49. The composition of claim 47, wherein the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain are included in an amount of 10.sup.4-10.sup.7 CFU/kg of the composition.
50. The composition of claim 46, formulated as animal feed, feed additive, food ingredient, water additive, water-mixed additive, consumable solution, consumable spray additive, consumable solid, consumable gel or injection.
51. The composition of claim 50, formulated as animal feed.
52. The animal feed composition of claim 51, wherein the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain are present in an amount of 10.sup.2-10.sup.8 CFU/kg of animal feed.
53. The animal feed composition of claim 52, wherein the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain are present in an amount of 10.sup.7 CFU/kg of animal feed.
54. The composition of claim 46, formulated for oral administration, nasal administration, or in ovo administration.
55. The composition of claim 46, wherein each isolated individual strain is free of other living organisms and the composition contains only the individual strains Lactobacillus reuteri strain 3632 (ATCC PTA-126788) and strain 3630 (ATCC PTA-126787).
56. The composition of claim 46, wherein the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain are formulated to be shelf-stable and exist outside the gastrointestinal tract.
57. The composition of claim 46, further comprising a prebiotic, wherein the prebiotic is galacto-oligosaccharides (GOS).
58. The composition of claim 46, wherein the animal is a bird, a human, or a non-human mammal.
59. The composition of claim 58, wherein the bird is poultry.
60. The composition of claim 58, wherein the animal is selected from chickens, turkey, dogs, cats, cattle and swine.
61. The composition of claim 58, wherein the animal is a human.
62. A probiotic composition for increasing animal health comprising an isolated first Lactobacillus reuteri strain 3632 (ATCC PTA-126788) and an isolated second Lactobacillus reuteri strain 3630 (ATCC PTA-126787), wherein the isolated first strain and the isolated second strain are present at a ratio of 0.75-1.5:1.
63. The composition of claim 62, formulated as animal feed, feed additive, food ingredient, water additive, water-mixed additive, consumable solution, consumable spray additive, consumable solid, consumable gel or injection.
64. The composition of claim 62, wherein each isolated individual strain is free of other living organisms and the composition contains only the individual strains Lactobacillus reuteri strain 3632 (ATCC PTA-126788) and strain 3630 (ATCC PTA-126787).
65. A probiotic composition for increasing animal health comprising an isolated first Lactobacillus reuteri strain 3632 (ATCC PTA-126788) and an isolated second Lactobacillus reuteri strain 3630 (ATCC PTA-126787), wherein the isolated first strain and the isolated second strain are present at a ratio of 0.75-1.5:1 and are included in an amount of 10.sup.2-10.sup.8 CFU/kg of the composition.
Description:
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Continuation of U.S. Ser. No. 17/428,510 filed on 4 Aug. 2021, which is a National Stage Application claiming priority from co-pending PCT Application No. PCT/US2020/016668 filed on 4 Feb. 2020, which in turn claims priority to U.S. Provisional Application No. 62/801,307, filed on 5 Feb. 2019, the contents of which are hereby incorporated by reference.
SEQUENCE LISTING
[0002] This application contains a Sequence Listing, which was submitted in ASCII format via EFS-Web, and is hereby incorporated by reference in its entirety. The ASCII copy, created on 4 Feb. 2020, is named "X30027-SeqListing_ST25.txt" and is 121 KB in size.
FIELD OF THE INVENTION
[0003] The present invention relates to probiotic compositions and methods for improving animal health. The probiotic compositions include one or more isolated strains of Lactobacillus sp which colonizes the gastrointestinal tract to increase the health of an animal.
BACKGROUND OF THE INVENTION
[0004] Direct fed microbials (DFMs), often also called probiotics, are microorganisms which colonize the gastrointestinal tract of an animal and provide some beneficial effect to that animal. The microorganisms can be bacterial species, for example those from the genera Bacillus, Lactobacillus, Lactococcus, and Entercoccus. The microorganisms can also be yeast or even molds. The microorganisms can be provided to an animal orally or mucosally or, in the case of birds, provided to a fertilized egg, i.e. in ovo.
[0005] The beneficial activity provided by a DFM can be the synthesis of vitamins or other nutritional molecules needed for a healthy metabolism of the host animal. A DFM can also protect the host animal from disease, disorders, or clinical symptoms caused by other, pathogenic microorganisms. For example, the DFM may naturally produce factors having inhibitory or cytotoxic activity against certain species of pathogens, such as deleterious or disease-causing bacteria.
[0006] There is a need in the art for probiotic compositions and methods that provide improved delivery of beneficial molecules to the gastrointestinal tract of an animal and improve animal health.
SUMMARY OF THE INVENTION
[0007] The present invention provides compositions and methods for improving animal health.
[0008] In one embodiment, the invention provides a composition having at least one of an isolated first Lactobacillus reuteri strain and an isolated second Lactobacillus reuteri strain, wherein said composition increases animal health when an effective amount is administered to an animal, as compared to an animal not administered the composition.
[0009] In one embodiment, the first isolated first Lactobacillus reuteri strain includes at least one of: a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO:26, a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 1, a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 3, and a nucleic acid that encodes for an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 8.
[0010] In one embodiment, the second isolated second Lactobacillus reuteri strain includes at least one of: a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO:25, a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 27, a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 28, and a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 29.
[0011] In one embodiment, the invention provides a method of increasing animal health. The method includes administering an effective amount of the above composition to an animal.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 depicts antimicrobial effect of L. reuteri strain 3630. Pathogenic bacteria, but not nonpathogenic Lactobacillus acidophilus are killed by L. reuteri strain 3630, as evidenced by a clear "halo" surrounding strain 3630. Pathogenic bacteria shown are gram-positive pathogens Clostridium perfringes, Staphylococcus aureus, Streptococcus uberis, Streptococcus suis; gram negative pathogens are Escherichia coli, Salmonella Typhimurium, and Campylobacter jejuni.
[0013] FIG. 2 depicts antimicrobial effect of L. reuteri strain 3632. Pathogenic bacteria, but not nonpathogenic Lactobacillus acidophilus are killed by L. reuteri strain 3632, as evidenced by a clear "halo" surrounding strain 3632. Pathogenic bacteria shown are Clostridium perfringes, Staphylococcus aureus, Streptococcus uberis, Streptococcus suis, Escherichia coli, Salmonella Typhimurium, F. necrophorum, and Campylobacter jejuni.
[0014] FIG. 3 depicts colonization of L. reuteri strain 3632 in chickens, via oral administration route. Left shows the experimental timeline. Right shows colony formation and PCR & sequence confirmation.
[0015] FIG. 4 depicts experimental timeline to determine colonization of L. reuteri strain 3632 in chickens, via in ovo administration route. Chicks were harvested at day 3 and day 7, and the strain is characterized.
[0016] FIG. 5 depicts colonies from chicks sacrificed at day 3. Strain 3632 is found in the tissues of chicks at 3 days post hatching, while colonization of a control strain declines after day 3.
[0017] FIG. 6 depicts colonies from chicks sacrificed at day 7. Strain 3632 is found in the tissues of chicks at 7 days post hatching, while colonization of a control strain declines after day 7.
[0018] FIG. 7 depicts characterization of L. reuteri strain 3630 and 3632 colonization in chicks via on ovo(spray) and in ovo administration route. Left shows the experimental timeline. Right shows CFU of L. reuteri strains 3630 and 3632 of chicks sacrificed at 3 days and 7 days.
[0019] FIG. 8 depicts data from birds vaccinated with coccidiosis vaccine on day 0 and fed with L. reuteri in feed from day 0 to day 42 @ 10{circumflex over ( )}7 CFUs/Kg of feed or with BMD_55. Top Feed conversion Ratio (FCR) of chickens administered L. reuteri 3632, as compared to chickens administered BMD_55 (bacitracin methylene disalicylate).
[0020] FIG. 9 depicts quantification of in vitro kill effect of L. reuteri strain 3632 on Clostridium perfringens. In a co-culture experiment, L. reuteri appears to inhabit C. perfringens growth almost by 4 logs. CFU counts were determined 24 hours after coculture in BHI broth. L. reuteri were enumerated on MRS agar plates and C. perfringens was enumerated on OPSP plates. This data is from one representative experiment of 3 replicates. Co-culture-L. reuteri, L. reuteri recovered from co-cultured sample using L. reuteri-specific media. Co-culture-C. perfringens, C. perfringens recovered from co-culture sample using C. perfringens-specific media.
[0021] FIG. 10 depicts the effect of prebiotics on the growth of Lactobacillus reuteri strains 3630 & 3632. The prebiotics tested include fructooligosaccharides (FOS), arabinoxylan oligosaccharides (AXOS), mannan-oligosaccharides (MOS), or galacto-oligosaccharides (GOS). Increased growth is observed with GOS.
[0022] FIGS. 11A-11B depict biochemical metabolic profile of two Lactobacillus reuteri strains. The figure represents metabolic data obtained by principal component analysis (PCA) of two strains of Lactobacillus reuteri that were cultured individually and together. FIG. 11A represents the cell pellet of the culture, 1_P-30 is the pellet from strain 3630, 2_P-32 is the pellet from strain 3632, and 3_P-30-32 is the pellet from a co-culture of strain 3630 and strain 3632. FIG. 11B represents the supernatant of the culture, 1_S-30 is the supernatant from strain 3630, 2_S-32 is the supernatant from strain 3632, and 3_S-30-32 is the supernatant from a co-culture of strain 3630 and strain 3632. 4_Medial is AOF-MRS media control with no glucose but 0.5% GOS.
[0023] For FIGS. 12-19, data represents subject molecule that is secreted into the supernatant. 1) Lactobacillus reuteri strain 3630, 2) Lactobacillus reuteri strain 3632, 3) co-culture of Lactobacillus reuteri strain 3630 and Lactobacillus reuteri strain 3632, and 4) media control. Data are scaled such that the median value measured across all samples was set to 1.0.
[0024] FIG. 12 depicts levels of dimethylglycine, allo-threonine, and 1-methyl-4-imidazoleacetate secreted by Lactobacillus reuteri strains.
[0025] FIG. 13 depicts levels of 4-imidazoleacetate, lysine, and N6-methyllysine secreted by Lactobacillus reuteri strains.
[0026] FIG. 14 depicts levels of N6, N6-dimethyllysine, 5-aminovalerate, and tyrosine secreted by Lactobacillus reuteri strains.
[0027] FIG. 15 depicts levels of 4-hydroxyphenylpyruvate, indolacetate, and gamma-glutamylglutamine secreted by Lactobacillus reuteri strains.
[0028] FIG. 16 depicts levels of glucose 6-phosphate, 4-hydroxyl-2-oxoglutaric acid, and myo-inositol secreted by Lactobacillus reuteri strains.
[0029] FIG. 17 depicts levels of Uridine 5'-monophosphate (UMP), Cytidine 5'-monophosphate (5'-CMP), and 3'-5'-uridylyluridine secreted by Lactobacillus reuteri strains.
[0030] FIG. 18 depicts levels of O-sulfo-L-tyrosine, indole 3 acetamide, and indolin-2-one secreted by Lactobacillus reuteri strains.
[0031] FIG. 19 depicts levels of daidzein secreted by Lactobacillus reuteri strains.
DETAILED DESCRIPTION OF THE INVENTION
[0032] The present invention provides compositions and methods for increasing animal health.
[0033] In one embodiment, the invention provides a composition having at least one of an isolated first Lactobacillus reuteri strain and an isolated second Lactobacillus reuteri strain.
[0034] In one embodiment, the isolated first Lactobacillus reuteri strain is strain 3632. As disclosed herein, strain 3632 has a nucleic acid or amino acid sequence including at least one of SEQ ID NOs: 1-24 and 26, sequences having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with at least one of SEQ ID NOs: 1-24 and 26. Lactobacillus reuteri strain 3632 was deposited on 19 Jun. 2020 according to the Budapest Treaty in the American Type Culture Collection (ATCC), ATCC Patent Depository, 10801 University Boulevard, Manassas, Va., 20110, USA. The deposit has been assigned ATCC Patent Deposit Number PTA-126788.
[0035] In one embodiment, the isolated second Lactobacillus reuteri strain is strain 3630. As disclosed herein, strain 3630 has a nucleic acid sequence including at least one of SEQ ID NOs: 25 and 27-43, sequences having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with at least one of SEQ ID NOs: 25 and 27-43. Lactobacillus reuteri strain 3630 was deposited on 19 Jun. 2020 according to the Budapest Treaty in the American Type Culture Collection (ATCC), ATCC Patent Depository, 10801 University Boulevard, Manassas, Va., 20110, USA. The deposit has been assigned ATCC Patent Deposit Number PTA-126787.
[0036] The isolated strains of the present disclosure are not genetically modified by recombinant or genetically engineered means.
[0037] In some embodiments, the composition disclosed herein includes an isolated first Lactobacillus reuteri strain and an isolated second Lactobacillus reuteri strain at a ratio of approximately 0.75-1.5:1. In a preferred embodiment, the composition includes about equal amounts of the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain.
[0038] The compositions disclosed herein can be formulated as animal feed, feed additive, food ingredient, water additive, water-mixed additive, consumable solution, consumable spray additive, consumable solid, consumable gel, injection, or combinations thereof. In one embodiment, the composition includes water.
[0039] The compositions disclosed herein includes the isolated first Lactobacillus reuteri strain in an amount of about 10{circumflex over ( )}2-10{circumflex over ( )}8 CFU/kg of the composition, about 10{circumflex over ( )}4-10{circumflex over ( )}7 CFU/kg of the composition, about 10{circumflex over ( )}3-10{circumflex over ( )}5 CFU/kg of the composition, about 10{circumflex over ( )}2 CFU/kg of the composition, about 10{circumflex over ( )}3 CFU/kg of the composition, or about 10{circumflex over ( )}7 CFU/kg of the composition.
[0040] The compositions of the disclosure exhibit markedly different functional and/or structural characteristics/properties, as compared to their closest naturally occurring counterpart. For instance, the Lactobacillus reuteri strain of the disclosure are structurally different from a Lactobacillus reuteri strain as it naturally exists in a gastrointestinal tract. To elaborate, the Lactobacillus reuteri strain can be isolated and purified, such that it is not found in the milieu of the gastrointestinal tract, the Lactobacillus reuteri strain can be present at concentrations that do not occur in the gastrointestinal tract, the Lactobacillus reuteri strain can be associated with acceptable carriers that do not occur in the gastrointestinal tract, the Lactobacillus reuteri strain can be formulated to be shelf-stable and exist outside the gastrointestinal tract, and said microbe can be combined with other microbes at concentrations that do not exist in the gastrointestinal tract. Further, the Lactobacillus reuteri strain of the disclosure are functionally different from a Lactobacillus reuteri strain as it naturally exists in a gastrointestinal tract. To elaborate, the Lactobacillus reuteri strain when applied in an isolated and purified form can lead to modulation of the gastrointestinal microbiome, increased weight gain, increased feed utilization, decreased amounts of microbial pathogens, and decreased pathogen-associated gastro-intestinal lesions.
[0041] Method
[0042] The present disclosure also provides methods of increasing animal health, wherein the method includes administering an effective amount of the composition to an animal.
[0043] The composition disclosed herein and above increases animal health by providing positive health benefits when administered to an animal, as compared to an animal that has not been administered the composition. As used herein, "animal" includes bird, poultry, a human, or a non-human mammal. Specific examples include chickens, turkey, dogs, cats, cattle and swine. The chicken may be a broiler chicken or egg-laying or egg-producing chicken.
[0044] Positive health benefits include decreasing feed conversion ratio, increasing weight, increasing lean body mass, decreasing pathogen-associated lesion formation in the gastrointestinal tract, decreasing colonization of pathogens, reducing inflammation, and decreasing mortality rate.
[0045] In some embodiments, the compositions disclosed herein decreases feed conversion ratio by at least 1%, at least 5%, at least 25%, or at least 50%. In some embodiments, the compositions disclosed herein increases poultry weight by at least 1%, at least 5%, at least 25%, or at least 50%. In some embodiments, the compositions disclosed herein decrease pathogen-associated lesion formation in the gastrointestinal tract by at least 1%, at least 5%, at least 25%, or at least 50%. In some embodiments, the compositions disclosed herein decrease pathogen colonization by at least 1%, at least 5%, at least 25%, or at least 50%. In some embodiments, the compositions disclosed herein reduce inflammation by at least 1%, at least 5%, at least 25%, or at least 50%. In some embodiments, the compositions disclosed herein decrease mortality rate by at least 1%, at least 5%, at least 25%, or at least 50%.
[0046] In some embodiments, following values may be combined in any manner to create a minima, a maxima, or a range for decreasing feed conversion ratio, increasing poultry weight, increasing lean body mass, decreasing pathogen-associated lesion formation in the gastrointestinal tract, decreasing colonization of pathogens, and decreasing mortality rate, 1%, 5%, 25%, 50%, and 75%.
[0047] For example, the decrease in pathogen-associated lesion formation may be decreased by approximately 1% to 5%, and more preferably between approximately 5% to 50%.
[0048] As used herein, pathogen includes Salmonella, Clostridium, Campylobacter, Staphylococcus, Streptococcus, and E. coli bacterium. Further examples of pathogens include Salmonella typhimurium, Salmonella infantis, Salmonella Hadar, Salmonella enteritidis, Salmonella Newport, Salmonella Kentucky, Clostridium perfringens, Staphylococcus aureus, Streptoccus uberis, Streptococcus suis, Escherichia coli, Campylobacter jejuni, and Fusobacterium necrophorum.
[0049] The compositions may be administered orally, parentally, nasally, or mucosally.
[0050] In some aspects, administration includes feeding the poultry, or spraying onto the poultry. In other aspects, administration includes on ovo administration or in ovo administration,
[0051] In some aspects the animal is vaccinated in conjunction with administration. The animal may be vaccinated prior to administration of the compositions disclosed herein. The animal may be vaccinated with an coccidiosis vaccine. Coccidiosis vaccines are known in the art, for example, COCCIVAC.
[0052] In some embodiments, administration is by way of injection or infusion. In one embodiment, the composition is administered to a cow by way of intra-mammary infusion.
[0053] The strains disclosed herein demonstrate certain phenotypic properties. Without wishing to be bound by theory, it is believed that these phenotypic properties at least contribute to increasing animal health.
[0054] In some embodiments, the isolated strains secrete at least one of cyclic dipeptides (cyclo(his-phe) and cyclo (phe-pro), short chain fatty acids (2-hydroxy-3-methylvalerate and alpha-hydroxyisocaproate), betaine, dimethylglycine, essential amino acids (e.g., allo-threonine, phosphothreonine, histidine, lysine, phenylalanine, tryptophan, leucine, isoleucine, and cysteine s-sulfate), nucleotides (e.g., adenosine 5'-monophosphate (AMP), uridine 5'-monophosphate (UMP), cytidine 5'-monophosphate (5'-CMP), and cytidine 2'3'-cyclicmonophosphate), myo-inositol, and indolin-2-one. Some of the aforementioned molecules provide beneficial characteristics to the host, including increased weight, pro-inflammatory effects, and antibiotic effects.
[0055] In some embodiments, the composition including the isolated first Lactobacillus reuteri strain (strain 3632) and the isolated second Lactobacillus reuteri strain (strain 3630) in combination, will secrete certain beneficial molecules in larger quantities than when individually cultured. See for example, FIGS. 12-19.
[0056] In some embodiments, the animal administered the composition exhibits a shift in the microbiome content of the gastrointestinal tract. For example, there may be an increase in the amount of bacteroidaceae bacteria in the gut of an animal that has been administered the composition described herein, as compared to an animal that was not administered the composition.
[0057] In some embodiments, the invention provides a method of treating, ameliorating the effects of, or preventing necrotic enteritis in an animal by administering a composition disclosed herein to an animal in need thereof.
[0058] In some embodiments, the invention provides a method of treating, ameliorating the effects of or preventing bovine mastitis. The method includes administering a composition disclosed herein to an animal in need thereof.
[0059] As used herein, "isolated" means that the subject isolate has been separated from at least one of the materials with which it is associated in a particular environment. Thus, an "isolate" does not exist in its naturally occurring environment; rather, it is through the various techniques described herein that the microbe has been removed from its natural setting and placed into a non-naturally occurring state of existence. Thus, the isolated strain or isolated microbe may exist as, for example, a biologically pure culture in association with an acceptable carrier.
[0060] As used herein, "individual isolates" should be taken to mean a composition, or culture, comprising a predominance of a single genera, species, or strain, of microorganism, following separation from one or more other microorganisms. The phrase should not be taken to indicate the extent to which the microorganism has been isolated or purified. However, "individual isolates" can comprise substantially only one genus, species, or strain, of microorganism.
[0061] In certain aspects of the disclosure, the isolated Lactobacillus reuteri strain exist as isolated and biologically pure cultures. It will be appreciated by one of skill in the art, that an isolated and biologically pure culture of a particular Lactobacillus reuteri strain, denotes that said culture is substantially free (within scientific reason) of other living organisms and contains only the individual Lactobacillus reuteri strain in question. The culture can contain varying concentrations of said isolated Lactobacillus reuteri strain. The present disclosure notes that isolated and biologically pure microbes often necessarily differ from less pure or impure materials.
[0062] In embodiments of the present invention, the composition includes a combination of two isolated Lactobacillus reuteri strains.
[0063] As used herein, "carrier", "acceptable carrier", or "pharmaceutical carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the compound is administered. Such carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin; such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. Water or aqueous solution saline solutions and aqueous dextrose and glycerol solutions are preferably employed as carriers, in some embodiments as injectable solutions. Alternatively, the carrier can be a solid dosage form carrier, including but not limited to one or more of a binder (for compressed pills), a glidant, an encapsulating agent, a flavorant, and a colorant. The choice of carrier can be selected with regard to the intended route of administration and standard pharmaceutical practice. See Hardee and Baggo (1998. Development and Formulation of Veterinary Dosage Forms. 2nd Ed. CRC Press. 504 pg.); and E. W. Martin (1970. Remington's Pharmaceutical Sciences. 17th Ed. Mack Pub. Co.).
[0064] As used herein, "delivery" or "administration" means the act of providing a beneficial activity to a host. The delivery may be direct or indirect. An administration could be by an oral, nasal, or mucosal route. For example without limitation, an oral route may be an administration through drinking water, a nasal route of administration may be through a spray or vapor, and a mucosal route of administration may be through direct contact with mucosal tissue. Mucosal tissue is a membrane rich in mucous glands such as those that line the inside surface of the nose, mouth, esophagus, trachea, lungs, stomach, gut, intestines, and anus. In the case of birds, administration may be in ovo, i.e. administration to a fertilized egg. In ovo administration can be via a liquid which is sprayed onto the egg shell surface, or an injected through the shell.
[0065] As used herein, the terms "treating", "to treat", or "treatment", include restraining, slowing, stopping, reducing, ameliorating, or reversing the progression or severity of an existing symptom, disorder, condition, or disease. A treatment may also be applied prophylactically to prevent or reduce the incidence, occurrence, risk, or severity of a clinical symptom, disorder, condition, or disease.
[0066] Unless expressly stated to the contrary, "or" refers to an inclusive "or" and not to an exclusive "or". For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
[0067] Any examples or illustrations given herein are not to be regarded in any way as restrictions on, limits to, or express definitions of any term or terms with which they are utilized. Instead, these examples or illustrations are to be regarded as being described with respect to one particular embodiment and as being illustrative only. Those of ordinary skill in the art will appreciate that any term or terms with which these examples or illustrations are utilized will encompass other embodiments which may or may not be given therewith or elsewhere in the specification and all such embodiments are intended to be included within the scope of that term or terms. Language designating such nonlimiting examples and illustrations includes, but is not limited to: "for example," "for instance," "e.g.," and "in one embodiment." In this specification, groups of various parameters containing multiple members are described. Within a group of parameters, each member may be combined with any one or more of the other members to make additional sub-groups. For example, if the members of a group are a, b, c, d, and e, additional sub-groups specifically contemplated include any one, two, three, or four of the members, e.g., a and c; a, d, and e; b, c, d, and e; etc.
[0068] Throughout this specification, quantities are defined by ranges, and by lower and upper boundaries of ranges. Each lower boundary can be combined with each upper boundary to define a range. The lower and upper boundaries should each be taken as a separate element. Two lower boundaries or two upper boundaries may be combined to define a range.
TABLE-US-00001 SEQUENCE LISTING mersacidin-E1 cDNA SEQ ID NO: 1 1 atggacaaag aagaattaga aaaaattgta ggtaataact ttgaggaaat gagtttacaa 61 aaaatgacag aaattcaagg tatgggtgaa taccaagtgg attcaacacc agcagcttct 121 gcgatttcac gggcaacaat tcaagtatca cgtgcatctt ctggaaaatg tctaagttgg 181 ggtagtggtg cagcatttag tgcttatttt actcataaaa gatggtgcta g mersacidin-E1 amino acid (natural) SEQ ID NO: 2 1 MDKEELEKIV GNNFEEMSLQ KMTEIQGMGE YQVDSTPAAS AISRATIQVS RASSGKCLSW 61 GSGAAFSAYF THKRWC mersacidin-E2 cDNA SEQ ID NO: 3 1 atggaagaaa aagaattaga aggtgtaata gggaattcgt ttgaaagtat gactgtagag 61 gaaatgacaa aaattcaagg tatgggtgaa tatcaagtag attcgacgcc tggatatttt 121 atggaaagtg ctgccttttc agctcttaca gccaatataa caagacatgc tatgcatcat 181 cattaa mersacidin-E2 amino acid (natural) SEQ ID NO: 4 1 MEEKELEGVI GNSFESMTVE EMTKIQGMGE YQVDSTPGYF MESAAFSALT ANITRHAMHH 61 H Capreomycidine synthase (natural). SEQ ID NO: 5 1 MVEIAHFGVE AWLNKWEKSA TYDISQSTIA SLSMHDLLNL DGNNGEEFYE MLDKQQMNYG 61 WIEGSPEFKE EVAKLYHHVD PENILQTNGA TGANILALYA LINPGDHVIA EYPSYQQLYD 121 IPKSLGADVD YWHIHEEDNW YPRIDDLKAM VKPNTKMICL NNANNPTGTV LDKEFLEQVV 181 EIAKSVDAYV LVDEVYLPLD HPEKFAQIID LYDKGISTNS LSKTYSVPGV RIGWTATNAE 241 VADIFRKFRD YTMICGGVFN DQLATYVLRH RDQVLARNRK LVLGNLAIYK DWIDHEDRAS 301 VIMPQAVSTS FPKLDVPVDI HTFCENLLHD EGVLLVPGDA FDTPGHVRLG YCAPEATLKE 361 GLKRLSKYMH QYD Colicin V production protein (natural). SEQ ID NO: 6 1 MILTTFIILI LMGCFINGHR RGLLTMTLML GTYIVAWIVA RQGAQLIGGW LKSLLPSIGT 61 PATFSESLLA NVNSNLFFYN GIAFMIIFTI VSILCHWGIR QLNWIKRIPV VGTVDKIAGG 121 LISFLIGYLI IYVVLLIMQL FPAGWWQMQI ANSELARFMI NQTPGIAHLV IDTLVQGG Agglutinin receptor precursor-1 (ARP-1) (natural) SEQ ID NO: 7 1 MNEYNAEMAK LNQGANAPVI TTNSVNQALS LKPENNATVD IEALNPRITF KRVEEGTKYA 61 GYQIFDKNNA YVNNIDGEFL RVTYTNLKNS TYKGSKISKI VVTYSDSTPT GNRITQSGLN 121 AVTEGANDNF LVVFEDPVRG DMHSTTVTAT YQYYDANGNL IDFSGTNNAW LSVGSLNFDQ 181 GNDYQGGKNE GNPTSGISEG VKLISGAQIK QLAGSSISVH DDGWAYAGFN NYSGTGMNNG 241 INTDNGGSGW DMDGSPNAYY GAIVFQLTGS SVSLRQGLVS WGGADIASQY NNQFLNNAWF 301 TAGTTLPETQ IKQPIRKTSE THYHYNPSVI RL Agglutinin receptor precursor-2 (ARP-2) (natural) SEQ ID NO: 8 1 MAQKLMSANS TDKNFKMYKS KKSWVFAYST TLALAAVAGI TLSTTNVHAD TTNGGDNQVN 61 ATAVTQNTTS NTVDQIAANT AQTDNTSTSI NIRSLMDDLA SGDDTSSSQN GQEQSQNYAS 121 SNQNSQTQQE NGTTGQSTAS QNGTTSDQTN SDQSDKNYYV ISTRDLDKNG NVNYLTQKNY 181 TSIKGQEVAD GTVVTWPLSV SALPANRAQD LKSHVISETL DPHLEYLHYR AYLTNTDGTV 241 TDVTNHVNLN RSGQTLIFTD DNYLLSIYNN NRYRVQNLPV IKLVTKANGN GYIIPNAFKS 301 SYVFNDGSHD VSFTTTSNNV QIKTFNPGNS KDVEIGGNVQ GDPSGTINGQ VVADGSVVTW 361 PMSVGDLPAN RAQDVLSHIE TDTLYNGLNY EGYHAYLPQA DGSFQDVSSH INVQQNGQDL 421 TFIADDYLIG LYNQDKSTAF KMPIIDLITS VHGTSIIAPN KFNSQLAFKD GNGQTVINNT 481 SNQVQISTYH PTNTKDVELG GNVQGDTPNS INDKVVANGA IVTWPMASSE LPANRVQDLQ 541 SRVISETLDS HLQYQGYKAW LQNADGKYTD VTSHVKLTQD GQNLTFADDE YLLNLYNSNK 601 GTAYKLPIID LVTKVNGAGI TAPNSYTTKY VYSDGDGNTT INVTSNTVKI STFNPTTNKD 661 VELGDNIHGD TESSIAGKLV SEGTIVTWPL STSDLPANRA QDVVSHTAVD ALEPTLQYIS 721 YTAWLPDSNG QLQDVTSHVK MTRDGQKLTF TDDDYLIGLY NQNKDIALKM PIIDLVTKAT 781 GNTKLLPNSF DSQFVYNDVD GNTIINVSSN KPTVETFDPT VHKDVELGGN NVQGDTPNSI 841 DGKIVAQGTV VTWPMSTSDL PANRTQDVVS HSTSETLNQN LQYVGYHAYM PDANGKLQDV 901 TSHVQLQQNG QNLVFTDDSY LINLYNQDKS IAFKMPIIDL MTKAISDSAT IPNTFESQYV 961 FNDGNGNTTF KSTSNTVQII TYKPKTTKDV ELGDNIHGDT NASIAGQMIT DGTVVTWPMS 1021 TSDLPANRTQ DLQQHVVTDN LNDNLIFQGY TAWLPTANGL VDVTNHIELT RDGQNLTFTD 1081 DAYLLNLYNQ NKDTAYKLPI IDLVTKANGN TKLIPNNFDS MFVYNDGDQQ TTVNVTSNTV 1141 NISTYDPTAT KDVELGDDIE GDTADTINNL MVQIGTKMTY PLTVSDLPAN RADEITAHQS 1201 VDTLSDYLEY QGYKAYLPDA DGKLQDITEH VNLKREGQKL SFNDDDYLIN LYNNSKATKQ 1261 ALPVIDLVAK VTGSNDGKKV HIIPNHFDST ITTKDGKINT TSNTVVINSN DPEAVKDVEL 1321 GDNVVGDTPN SVTGTTVADG TIVTWPMSVG SLGANRAQNV IKHTETENLD SGLTYLSFKA 1381 YLPDADGKMQ DITEHINIQQ DGQKLVFTDD DYLISLYNKD KSQRFALPVI DLVTRVNGDN 1441 KIIPNTFVSQ FTFNDGKGNT ITSVTSNQVN VSTFKSNPEK HVTLGTDIEG DDAENADGTV 1501 VAQGSEVTWP LSDKSPLPAN RSQDVKSHTL VDKLDDNLQY NSYKAYLKGT DGKLQDVTDH 1561 IKLTRDGQNL TFIDDDYLLD LYNKDKSTAF NLPIIDLVTT VVGNDKLIPN KFDSNFVFSD 1621 GNKDTSMKTT SNEVSISTYT PVTNKDAELG DNVVGDTSDS IANETVPDGT IVTWPLSVSS 1681 LPANRSQDVF KHVIEDILDG NLTYNSFKAY LKDAAGNLQE VTDHVKLAQE GQHLTFTDDD 1741 YLINLYNSSK NKEQSLPIID LVTTVHGDSK LIPNEFDNVF VFKDGKGQTT VKTTSNKVTI 1801 KTASLPTPTK EETDDQGNNI NGNEVKAGEH VNYTLNWDLS NDKDVKATPE MIKKGFFFID 1861 PIDSRALSVD DLSKAKVVDQ NGNKVDGISF HLYNSLSEVP EFIQEQVKAN NLQDKITGPF 1921 VVAQADDLQA FFDKYVKTGA KLKVTIPTIV KSGFTGEFSN TAYQFGFGKA TPTNTVTNYV 1981 KPMHKPASPE TPAAIAPQVI SATAQPMTSD APVTPSEKTA KLPQTGNADE GALLGLAAVS 2041 LVGSLGLAAL GLKQNRNDD Xylulose-5-phosphate phosphoketolase promoter (natural) SEQ ID NO: 9 1 TTAAAGTATT AAAATAGATG TAAAATTTAT TTTTTTCAAA AGAAATTTTA ATTGTACACT 61 GTTGGTATTG AACGGGGTTA AACAAAGGTA AATTAGCATT TCTGCGGATT AAGATAAATA 121 GAAAAATGTT AAAGAACACC TTAAAAAGAT TAATTTTTTA TAATTGGACC GTATCAATTT 181 GTAAAAAGGT TGACTTTTTG AAAAAAAAGT TTATCATTAA CATTGTAAAT TTAATGATTT 241 ACGTTATGTT GTTATAGAGC ACAGGACGTA TTGATTTATA TAGAAGGAGT GTTTATTAGA Elongation factor TU promoter (natural) SEQ ID NO: 10 1 ATGAATGGAC AGATGTTTTA ATCGCTAGAA TAGAAGGAAA GAAAGTCGCA ACAAATACGG 61 TTTCTAGTAC GTGGCAGGAA CGACTAGGTA AGCAGATTGA CGAATTAATA GAAAAACATT 121 AGTCAAATAC ATTTACAAAT GAACAGATAG TTGATATTAT ATTTAAGAAT TCTTCTTCAG 181 AGCCTAAGAT TAAAGCTTTC AATTGGCGAA AAGAAGTTGT ACAATATGTA TAAAGGTATG 241 TCAGTCACCG AATCAGATGA TCTGGCATTA TACTTGTAAA TTATCAGGAG GTTTTCATTA Glyceraldehyde-3-phosphate dehydrogenase promoter (natural) SEQ ID NO: 11 1 ATCTCACGTG CGATCCATTA CACTAAGGGC GCGTCAACAA ATATTATACT ATCTTAAATA 61 AGAATGAATT GCAAGCATTA TTTGAAAATT TTAATTAAAA TAACGCTTAC ATCAGAAAAA 121 TGTTGTGATT GAATAGACAA TTTTTTTGAA GATGGTATCA TAAGTATCGT AGGAGTTGTA 181 TTATTGCTTA GACCTTACCA CTGCGTCACT TACAATGGTT GAGAGTTGCG ATGCTGATGT 241 AATGTGATAA ACTAAGCAAG TACACTAATT ATGTTTTTTC CTAAAGGAGG AATTTGCAGT Glucose-6-phosphate dehydrogenase promoter (natural) SEQ ID NO: 12 1 TTGTTTAAGA TATCTTTCAA AGCTGCGGAA TTTTTCCCAG CTTTTTTAGT TAGTTTTGTT 61 TTCATAAGCT ATAATTTTAA CCGATTCCAA ATTTCTTTTA AAAGTTTTTT TGATCTAGAC 121 CATTAATTGA TAAACGCTTA CCAAAGACTA ATCAACAAGC CATTTAGCGG TAGTGGTCCA 181 TTTTAACTTT CTAAGACATC TTCTCAGAAA ACGTTTCCTT TGATAGTGCA GATTGTGCTT 241 TAAGAGTATA TAATTGTCAC GGTATAAGAA TTTTCTGAAA TTTCAGAAGG AGTGAACATT L-lactate dehydrogenase promoter (natural) SEQ ID NO: 13 1 CTCCTCTATT ATTATTCCTG ATCAATTTTA AATTAATCTC CCTAGATAGG TATATTTTAG 61 CACAGGTCAC CAACGTTCCA AAGTTTAATC TATGTTTAAA CTTTAATTTT CAAAAAAATG 121 CTATACTATG TTCACGATAC TTTAAGGAAA GGTGATTACA ATAGTGAGTC TCTTAATTGC 181 TATTCTTATC TGCTGGTTGC TATGGAAGAT TGGGGGTTTA ACGGTTAAGT TCATTGGTCT 241 AATCCTTCTT ATTCTATTAA TCGGGACATT AATTCATGTT TTACTTTGGC CAGCGATCCT 301 TTTAGCAGTT ATTATCTTAG GAGCAGGTTT ATTCACTAAC TAATTTATCT ATAAAATCTT 361 ATAGTAATTT TTCTGCGGAA TGTTATAATC ATTACTGTGA GAGAAATCTC AAATAATGTA 421 TACATAAGAT GAAAGGGAGA CTGTTTATT tuf promoter (natural) SEQ ID NO: 14 1 ACAAATACGG TTTCTAGTAC GTGGCAGGAA CGACTAGGTA AGCAGATTGA CGAATTAATA 61 GAAAAACATT AGTCAAATAC ATTTACAAAT GAACAGATAG TTGATATTAT ATTTAAGAAT 121 TCTTCTTCAG AGCCTAAGAT TAAAGCTTTC AATTGGCGAA AAGAAGTTGT ACAATATGTA 181 TAAAGGTATG TCAGTCACCG AATCAGATGA TCTGGCATTA TACTTGTAAA TTATCAGGAG 241 GTTTTCATTA C protein alpha-antigen precursor (natural) SEQ ID NO: 15 1 MVSKNNHQFY QQKHAERKQR WGIRKLSVGV ASVLLGTTFM LYGNHAVLAD TVTSPSDDVT 61 RSTTTQGGNK DKVTEGTTEG TTSTPQTSGD STDKQANGQN VNQQVPTTDT EEATNHQDTP 121 QGQDTTQNTT NVDKKDTEVT PANDATTPTT QKITAKFTTA KFTTAKFTAA KFKVLAARPV 181 MKVAGTASLP ISNQDIKLDS QPMLTEIINK PTDNWVYNNL KWYQDTSTEK IKEILQNHTA 241 NDESGRYYFA GVANYNEHYH AIYLLARSNN LNDNSLYVTI LHTGLGKNIQ EAVVAPGESK 301 KVEYSGTTHT PIFTNYDGTS ASIDLDGIEK GDNIYGMVVG FAYGHNTGIK GDPASMGNGF 361 VMTPIPTKMT TTIHYIDQAT GDEIAVPKSF EGVAYQKYTI TGEAPTIDGY TLKKSPETTG 421 YISPYKVGES YDFRLDKHVV IKQTVIDAQG LVRVTAYYDG EVLNNTTRYL GNKLNVNDRM 481 SFISHGKWYT YINQITSTND GIVYYYAKDG SEDKSEVRVH YIDVTGSKNS IFVPGDGEEV 541 ATDKISGKLG ENYNYDVNLP TDYNLATNQA NTVNGTYTID HHDEYVYVVK KTSAELDPTV 601 PAKTKVDNPT SLTADEKKTI EDKIVEANKD KFPEGTGVTV ANDGKATITY PDKSVDTIEG 661 NQLVEEKTSA EKLDPTVPAK TKVDNPTSLT ADEKKTIEDK IVEANKDKFP EGTGVTVAND
721 GKATITYPDK SVDTIEGNQL VEEKTSAEKL DPTVPAKTKV DNPTSLTADE KKTIEDKIVE 781 ANKDKFPEGT GVTVANDGKA TITYPDKSVD TIEGNQLVEE KTSAEKLDPT VPAKTKVDNP 841 TSLTADEKKT IEDKIVEANK DKFPEGTGVT VANDGKATIT YPDKSVDTIE GNQLVEEKTS 901 AEKLDPTVPA KTKVDNPTSL TADEKKTIED KIVEANKDKF PEGTGVTVAN DGKATITYPD 961 KSVDTIEGNQ LVEEKTSAEK LDPTVPAKTK VDNPTSLTAD EKKTIEDKIV EANKDKFPEG 1021 TGVTVANDGK ATITYPDKSV DTIEGNQLVE EKTSAEKLDP TVPAKTKVDN PTSLTADEKK 1081 TIEDKIVEAN KDKFPEGTGV TVANDGKATI TYPDKSVDTI EGNQLVEEKT SAEKLDPTVP 1141 AKTKVDNPTS LTADEKKTIE DKIVEANKDK FPEGTGVTVA NDGKATITYP DKSVDTIEGN 1201 QLVEEKTSAE KLDPTVPAKT KVDNPTSLTA DEKKTIEDKI VEANKDKFPE GTGVTVANDG 1261 KATITYPDKS VDTIEGNQLV EEKTSAEKLD PTVPAKTKVD NPTSLTADEK KTIEDKIVEA 1321 NKDKFPEGTG VTVANDGKAT ITYPDKSVDT IEGNQLVEEK TSAEKLDPTV PAKTKVDNPT 1381 SLTADEKKTI EDKIVEANKD KFPEGTGVTV ANDGKATITY PDKSVDTIEG NQLVEEKTSA 1441 EKLDPTVPAK TKVDNPTSLT ADEKKTIEDK IVEANKDKFP EGTGVTVAND GKATITYPDK 1501 SVDTIEGNQL VEEKTSAEKL DPTVPAKTKV DNPTSLTADE KKTIEDKIVE ANKDKFPEGT 1561 GVTVANDGKA TITYPDKSVD TIEGNQLVEE KTSAEKLDPT VPAKTKVDNP TSLTADEKKT 1621 IEDKIVEANK DKFPEGTGVT VANDGKATIT YPDKSVDTIE GNQLVEEKTS AEKLDPTVPA 1681 KTKVDNPTSL TADEKKTIED KIVEANKDKF PEGTGVTVAN DGKATITYPD KSVDTIEGNQ 1741 LVEEKTSAEK LDPTVPAKTK VDNPTSLTAD EKKTIEDKIV EANKDKFPEG TGVTVANDGK 1801 ATITYPDKSV DTIEGNQLVE EKTSAEKLDP TVPAKTKVDN PTSLTADEKK TIEDKIVEAN 1861 KDKFPEGTGV TVANDGKATI TYPDKSVDTI EGNQLVEEKT SAEKLDPTVP AKTKVDNPTS 1921 LTADEKKTIE DKIVEANKDK FPEGTGVTVA NDGKATITYP DKSVDTIEGN QLVEEKTSAE 1981 KLDPTVPAKT KVDNPTSLTA DEKKTIEDKI VEANKDKFPE GTGVTVANDG KATITYPDKS 2041 VDTIEGNQLV EEKTSAEKLD PTVPAKTKVD NPTSLTADEK KTIEDKIVEA NKDKFPEGTG 2101 VTVANDGKAT ITYPDKSVDT IEGNQLVEEK TSAEKLDPTV PAKTKVDNPT SLTADEKKTI 2161 EDKIVEANKD KFPEGTGVTV ANDGKATITY PDKSVDTIEG NQLVEEKTSA EKLDPTVPAK 2221 TKVDDPTKLT NDEKKEVEDN IRDHNTGLPE GTKIAVGDNG DTTITYPDKS VDTIEGNQLV 2281 EEKTSAEKLD PTVPAKTKVD DPTKLTNDEK KEVEDNIRDH NTGLPEGTKI AVGDNGDTTI 2341 TYPDNSVDTI PGDKVVEGKS DAAKNEPKVP GDKVKVDDPN KLTEDEKSEV VKAVEDANKD 2401 ENGKSTLPEG SKVTVGDNGD VTVTYPDGSK DTIPGDKVVE GKGTEGQTDA DKNEPKVPGD 2461 KVKVDDPNKL TEDEKSEVVK AVEDANKDEN GKSTLPEGSK VTVGDNGDVT VTYPDGSKDT 2521 IPGDKVVEGK GTEGQTDADK NEPKVPGDKV KVDDPNKLTE DEKSEVVKAV EDANKDENGK 2581 STLPEGSKVT VGDNGDVTVT YPDGSKDTIP GDKVVEGRGT EGQTDADKNE PKVPGDKVKV 2641 DDPTKLTEDE KSDVEQAIKD ANKDENGKST LPEGSKVTVG DNDDVTVTYP DGSKDTIPGD 2701 KVVEGKGTEG QTDADKNEPK VPGDKVKVDD PNKLMEDEKS DVEQAIKDAN KDENGKSTLP 2761 EGSKVTVSDN GDVTITYPDG SKDTIPGDQV IEGKSDADKN TPNVPGGDKV KVDDPTKLTD 2821 NEKNAVKDKV DEANSNLPDG TKVTVGDDGT TTITYPDGST NTISGHDLVT GKTDADKYPL 2881 NPGQAVNVVD PNHLTQAEQD QVKEAIQTTN PTAPIATITV DTAGNVQVTF ADGSTTTLQA 2941 NLHKHVTEAT TGSAIKPGVG TNGGQTKGAT STNQTATKQQ AQQHLPQTGD QPATWAMLSG 3001 LGVAFLGLLG LKKKRED Arabinogalactan endo-1, 4-beta-galactosidase (natural) SEQ ID NO: 16 1 MEIKKHFKLY KDGKKWCCAA IATTVLGIGL AIGSPSVLAD ADTITSTSDA NNSLVKNDNT 61 SDTDSNSEST FTDTNKNSTN EKEINENKNI DSSQQINQEQ TKSNNSEEQT TPVNVKAENT 121 DIKDSIPEKS TPNSFKEING STYYYGENGD LYRNQFYNNW GRTYYFQANG ARLDNGFYNN 181 WGRTYYFGSD GARWDNRFYN NWGRTYYFQN DGSRLDNSFY NNWGRTYYFG VDGARWDNRY 241 MVKWGRAYYF GNDGALLQNQ LKSINGINYW INNEGIIPLK NQFLTANENQ LFYFDGNGSL 301 VVNKFYHNWG HTYYFGSDGA RYTDQFLNRD GKVYYFDNQG IMYQDQYYKN WGHTYYFGSD 361 GARYTDQFLN RDGKVYYFDN QGIMYQDQYY KNWGHTYYFG SDGARYTDQF LNRDGKVYYF 421 DNQGIMYQDQ YYKNWGHTYY FGSDGARYTD QFLNRDGKVY YFDNQGIMVT NQVRVIDGKG 481 YEFNDNGEAT ETSDMGQTRD TVAKEVAQAL TNQGIKGVKY DWRNTNNDYQ ELALHDIAQE 541 VAQGDTNPDK NVIEKKLQAN NLLSGKVLVV YSTDFTNDDP QKITNTFMNS YDFTNADNSV 601 LGVGADLNKN KLVIILFKPG EKAEQPQATS TISASISDIF KKAGVNVDVD NGLTKGSVVN 661 SADLGNALTN GTAELLKGDK GTIISQEVLK AIFAAFAGNT SAVEGTKNYY NGNDAYHYEF 721 WLEGQSADDK LNNFLALNKG AKYGDQLKVN YTATLVFGQE TGTNSNESKV PASERTDEQL 781 DLAYKTGTDT GLRYDSVKVE KIPGMTDDMV RGVDVSSYQA LINAGVKFYD FNGQESNLFK 841 ILKDSGVNWV RLRVWNDPYN AQGQPYAGGD NNEENLIKMA KEASDNGLKL LIDFQYSDFW 901 TDPAQQILPK AWRNLSHGEM SQEVYLYTSK ILNDLQKAGA SVKMVQIGNE ITNGAFGLYT 961 GRNGGGNWAS LWETSDGDQV AKYIQAGSSA VRRIDPTIKV AIQLETPEIN KYRGIMNVLK 1021 KNNVDYDYLG TSYYPFWSTT QGNGWYDNVD LGYGANTPVN LEAIEKMAWN EFGKRTVILE 1081 SGWLNNTNDA DGTHNSVGEN NETTNIDRYS ADPQGQVDEI EDMYNAIIAQ KGLGAFYWEP 1141 AWIPVKAGWN NWQYNKLMSN IYGSGWASQY AKGYAPDSVL YYDGKEAWGG SSWDNISLFD 1201 DHGHPLQSLN VYNGMLNGYE SPKNVKSSLS TQLVKIWNET DVIPNDGLTE GTKLSTDLFG 1261 TTQLSGNDGQ SIGNAELTKL AGRLKDGISS KVYTAANGAR YHYIYWLEGG NNKVNTFVSA 1321 NKDAKYGQPL IANYSATVVV DSEPGTQVAT SPLQIKISQV WNTVNNEEIK IDNPLKQGDL 1381 ITDKSDNAFS GILNSKDIKE ALTGEKGKDV SESTVNDVKS LLPKEVKGSK TYTTADGNQY 1441 YYDFWLASVE TSNVNYGEPI IVNYTASLKW LG Chromosome segregation protein (natural) SEQ ID NO: 17 1 MEKTMKKKAL VATTAVAGIT LVGEVTTVHA ADNVQQPVNE QNVNQSSQEE KQAAQNLQNA 61 QSDVNTATEA NSNAQDNLAS ANNNLSNAKK AVSDQAAKVA DATKAQSDAS TKVDNDNKVV 121 ADAQQKADQA TPANIENAKQ AIEGQNKVID QDNENIKYSN TDQDKAQNTL NNAQSNEDKA 181 NATLSNKKSS QASAQNNVKQ AEDALNGTHL VEAQNAFNQA QSNVENAQSK YDQANNQLSD 241 AQKKVTTNQN DLTAKNKALD NINNQVDTDQ NNVNSNQATA DSASSATQVA QNAVDQTKQS 301 LDKVIEELNG FSENTIKVPA GAQEAYEAFI DAVDNNADQS QLDSLAKKMY DTLHQGQGTN 361 GINHFNSSKY DQNQLVDVDH LTTDQLNELT QFAADMINSA RKAWGSDKNA GTLIPTQGVS 421 EMAQQIAKGY VSDNWHISQG HDVKRVTAAA GLIGLNDAGQ FYEDASEGYV HAWPWEKDSY 481 TMDNLKEAVY DSILGMLFAD DNSGNGHMTD LLGLHVNRKE DHQYFGLSTN MCPGSYMGQL 541 HFIIVENDPA YIKDPQTFNA KGGTTKIEYI DPKVQLNQQK DILTTTLSTQ QADLATKQDA 601 LNKANQNLAN AKKQLSEDQD LQTVAQQNRD SAQKALNDAT AKVSNLQATV NSLSQDLNSA 661 KATLDQAKKT LESYTADHKA KLDNYNNAKA ALDDANKAVA EAQSAVDTAV NETKIAQNNL 721 DQKKQAVTDA QNKLANDQEY LATLKQNLAD LQNAPQNLQK AKDQLAKDQI ALDNANKDLQ 781 NQKDSLDELN KKLEDAQVKV NEAQSAANVT KATLDQAQAK LSDAEATWKE LHNDAHRYGN 841 VVKVTPITME AGTSLPDPVI ENGFTVNTGT NQLFVSLAAI DSSNNNIPQG TKASWANRSK 901 ALTDSQNAGS YSEDILITFP DNSTVTVPVD LTVTAKKITE DQKATEGGYH IVNGSVVDKQ 961 NNLVSGWTVK NGQMVDPEGN VIKTTMSTAQ GVTIEKNNSK SGNTKTNMIQ TSLTIANNKA 1021 TTNKDNQLPQ TGNYNNNTKV LGLAGIALAS ALTMFGYKKR QHN D-gamma-glutamyl-meso-diaminopimelic acid endopeptidase Cwls (natural) SEQ ID NO: 18 1 MKSTTKKILA SSLGVAGAMA MGTVTAKADT TVTVNAGDSL NGIAQKYNVS ADDIATANHL 61 QNKELIFVGQ KLTIPTKDKN ETPANNAEKK DQASKNSQSL QDSVNKAMSY LGTPYVWGGN 121 KPGGFDCSGL VQYCYGIPQR TTYEQQALGP HIHDNVLNAP YGALVFYGSD DAPYHVAISL 181 GDGRIIQAPN ENETVKITDQ QYFPGNYYVV MH N-acetylmuramoyl-L-alanine amidase sle1 precursor (natural) SEQ ID NO: 19 1 ATGCGTAATC AATTCATCGA TGTTTCAAGT TATCAACCAG ATACTGTTGC CTTTTTCCAA 61 GCTGCTAAAG CTCAGGGTGC ATTAGGGGTC GTTGTTAAGT TAACGGAAGG GTCCGAAGAT 121 GGTTCGGCTT ATGTTAATCC ACGTGCGGCC GCTCAAATTC GTAATGCCTT AGCGGTTGGC 181 TTGCGCGTTT CCTGTTACCA CTTTGCTCGT TATACATCAG TGACTGATGC ACAAAATGAA 241 GCTCGATTCT TCGTTAAAAT CGCTAAGCAA TTTGGTATGT ATGACGATAC TTTGATGATT 301 GATGATGCGG AAGTTCATTC AACTGCAGAT TATCAATCAG TATCCTTAGC CTTTCTTCAA 361 GAAGTAGAAG CTCTTGGTTA CAAGAATACT GGGATTTACT CCATGAAGTC CTTCTTCACT 421 GGCGGTATTC TTAATTCACA TGGCTTTGAT TCCCGGAAGA TTTGGATTGC TGGCTATGGT 481 GTGACTGAAC TGGGGATTGA TAATGCAAGT GCTTGGCAAT ATTCTGATCA TAGCATCATG 541 GGAATTGATA CTAGTTATGA CTTTGACGGT GCCTTTACGA CTGGTTTAGT ATCAGGCAAT 601 GTTCCGCAAG CTGTTATTCC AGCACCACAG CCGGTTCAAC ATATTGGTCA CCCAGCTACT 661 GGAACCTACA TTGTTCAGCC GGGCGATACA TTGAGTGGAA TTGCAGAAAA ATACGGGACT 721 ACTTATCAGA ACCTAGCAGC AATCAATGGT ATTGGTAATC CAAACCAGAT CAATGTCGGC 781 CAAGTCCTCA AAGTCACCGG AAAAGTATCA AACGAAAATA CTTACTTTGT TCAATCAGGC 841 GATACGTTAT CCGGAATTGC CACCAAATTC GGCACCACTG TCTCAGACCT CGTAAGCCGT 901 AATCACATTA CTAACCCGAA TGTGATCTAC GTTGGGCAAA AACTCTACTT AGCCGGCAAC 961 GGACAATCCA ATGCTTATAC TGTCCAAGCA GGGGACACAC TAAGCGGAAT TGCGGCTAAG 1021 TTTGGCAAGA CCTGGCAAGC ATTAGCTCAA AAGAATGGCA TCGCAAATCC TAATATGATT 1081 TTCATTGGTC AAACAATTCA GATTTAA Peptidase family M23 (natural) SEQ ID NO: 20 1 GTGTACCGAA TTATTGGTTA TAATGAACCA ACAGATAAAG CAGGATTTAT TGTACTGGAT 61 CCCCGAGTTA ATCGTCATAT TAGTTCGGGA AAACTCACGC TTAAAGAATC TAATATTGAT 121 GATTTGACTA TTACGGTTAA TCAAGCAAGT CCATTATGGG ACAACGTAAG GCCTTATCAT 181 ACTCATGTTA ACGTTTATGA TGATAATGAA CTTATTTTTC GTGGACGAGC TATCAAACCT 241 AAAAAGTCGA TGGAAGAAAG CGGACAATTC ATTCGTGAAT ATGTTTTTGA AGATATTGAA 301 GCATATCTCA TGGATAGCAC CCAAAGATTT TATGAAGGTG TTGGTCAAAC GCCCAAAGAA 361 TTTTTACAAA CTTTAATCGA TGTTCATAAT TCACAGGTTC CTGACTATAA AAAGTTTCAA 421 GTCCGGAATG TAAATGTCAC TAATAATAAG GATGACCAAT ATCGACAAAT TGATTATCCC 481 AAAACTAGCG ATGCTATTAA TGATAAATTA GTTAAATCTC TTGGTGGTTA TATTGTGACT 541 ACTTACAACG CTAACGGAAT AAACTACATT GACTACTTAA CGGATATTGG GGTTGATCAT 601 AAAGATGATA CTCCTATTCA GTTAGCTAAA AATATGAAGT CTGCAAGTAT GCAAATTGAT 661 CCTACTAAGG TGATTACAAG ACTGATTCCA CTGGGAAAGA CACTAGAACC ATCAAAAGTT 721 GATGTAAGTG ATGATGATGG AGAGGGCGGT TCTGGATCAT TAGATAGCCC TGAAGAATTT 781 TGTAAATCAG AAATTAATGC TACTTGGGGT AGTGATATTA ATAATATGAA ACAAGATTTT 841 GCCGCTCGTT CTTCGAGAGT TCGGGCTTGG GGAGTGGACG TTAATCGTTT ATATGATGTG 901 GTGAAAAATG CTGGAGTAAG TCCTGAATGG TTCTTTGCTT ATGAACTTCA AGAACAAGGA
961 ACTTACTATG GATGGCTTAA CCATACTTAT CGACACGGTG ATGCGTATAG TGATGCGCAA 1021 TCTGTTTGTG AGTGGATTAA AAATTGTTCA AATAGTAATT CCATTAATCC AGCATGGAGC 1081 GCACCGGAAG GATCAATGGC GCCGAATCAA GCATTAGCGG ATAAATGGAA TCAAGAGTTT 1141 GGAAAAGGTA CTATTGGCCG CGTTTATTTA CAAGGGACTG CCGCTGCTGT TTGGGATTTA 1201 GCTGGTCAAA CGCCTAATCC AGCTATTGGA AAGCCAATTA GTGGATGCAT TTCTTGTATT 1261 AAACGTTGGG GTGGTCATTC TAATGCAGCT GGTGGTACAT GGGGATGGCC TTTTCCTGAT 1321 GTTGGGGAAG GTCATTTTTC TCAAGTTCAG AGTTTCGGAA ATGATGGCGG ATATCGTCAA 1381 AATAGTTATC ACGATGGTGT GGATTTTGGA TCAATAGATC ATCCTGGTAG AGAAGTGCAT 1441 TGTATTCATG GTGGAACGGT AACTATCAAA TCAGCTATGG GTGGCTTAGG TAATTTTGTG 1501 GTTATTCATA CGCCGGAAGG ATTCAATATC GTTTATCAAG AAGCTTTTAG TTCTCCCTCT 1561 AATATTATTG TTAGTGTTGG GCAAAAAGTA AAAACTGGTG ATGTAATTGG ATATCGTGAT 1621 ACAGACCATG TTCATATTGG CGTAACTAAG CAAGATTTTT ATCAAGCAGT TCGAAATTCT 1681 TTTTCTCCTG CAGGTGGTTG GCTAGATCCA GTAAAACTAA TTAAAGAAGG TGGCGATGGG 1741 TCTAAACCAC AAGAAGGAAA GAAAGATCAA ACTGTTGATA ATAGTAATGC TGCACGTCCT 1801 AAATTAACCA TTACTACTGT CAATAACGGT AGAGACTATA TTGATATTCC TGATTTACAA 1861 AAAGAATTCG GTATTATTGA GGGAACTGTT GAATTTGATA ATGTAGATGA TCCGAATGTT 1921 TTAATGCAAC AAGCTCAAAC ATGGATAAAG GCTCAAAGAA TACCTCAAAG TTGGGAAGTT 1981 ACAGCTTTAG AATTACATAT GACAAACTTC AAATCTTTTA AGGTTGCTGA TAGGTACATG 2041 TTTATTAATC CAAATGTTGC AAAACCCCAA TTATTACGAA TTACTCAAAA AGAAATTGAT 2101 TTACTAAAGC CCCATGCGTC TTCATTAACG ATTGGTGATA AGACGATGGG GCTTACTGAT 2161 TATCAGTTAG AAAATCAAGT CAATTTTCAA CAATTTAAGG AAATTCGAGT GATGGTTAAT 2221 CAGGTTGTCC AAACCCAAGA GCAATCTGCT AATAACAATA ATAAGGTTAT GCAAAATTTT 2281 GCTAGTAGTG CTGATCTTGC ACAAATGAGA CAGGATCTAA GAAATCTTCA AGATGATAAC 2341 GATCGTGCTC GCAAAGGAAT GGTTTCCTTA GAAGAATTCA ATAAACTAAA GGAACAAGTA 2401 GAAAAACTAA CAACAGGAGG CGATGATAAT GGCAAGTGA Chromosome Partition Protein Smc (natural) SEQ ID NO: 21 1 MNKANQKVAD DTTAVNNKQT DVNNAAEAKK NADEALKNAN DAQTSAQKNK DAKQAIADEA 61 SVALADANTA VKDAQAKVDA INDKLANFNT ITLPAGYKDD LIAYYNYFGN SNYNQDEANN 121 LAQDLLKYRD QAMSQNKFKD NLSDDRVVDI DNLNSTDRAE LSQFVASLIN QVRTQMGTNL 181 VISSPAADDY AEQVSQNYNK DNWNSADNGK HDQSALNNAT DQLNISWNGE NMGLDQSIFT 241 TDYTVLTDGT KLPTGNKQTI NDLKHLIYDD FISMMFDDAD SAWGHATNFA GIDNFAAEKQ 301 AVGFSLDKFY NTHYDLVEAN QKVEENSYTL PSINALTQKL ADAKDDLSIK QTDQASKQKA 361 NDDAQNALSS ANQVLVAAQN DVKDKTATAQ EANDNLTTAQ NDLATLQNQL SADQANQKQA 421 QTTFDSFDAD LATKQANLQK ATDSLKAEQG RLAIAQADLD NANKALSDAN NNLAQKKQVV 481 ENDNETLKVD NDKLVQLQNN LSDLQNAPKL LAAAKEQVAT AQKALADAQE AYNVANDKLT 541 SLKQTAAGTT TNVSKAQQAL AEAKNNEDAA KEVLDQAQQA LTELRQKEAL AKQVAEEQAK 601 LAAEKEAKDN GYHIENNQVV DAKGNSVNGW TVKGNQIVSP TNATVDPAVS VTTNVNVDSK 661 GQVQPQTSVT ANSVKTVAAT ESANPVATTT VQTREQYKQQ LKSNNQLPQT GNNDSAVLSL 721 AGVALAAMLS LFGIKKREY Cwls endopeptidase promoter (natural) SEQ ID NO: 22 1 AAATTAAAAG GCTGGATTTT TTCGGCCTTT TTTTAGTGCA AATAATTATT TTTTACGTAT 61 TTATATTATA GGGCTAATCA CTAAACTAAT AATTAGTGGT TGAAGCGCTG AAAATTTTCT 121 GCTATTTTAT TAATAGTTTG ATAATAAAAT AATGATATTT AATATAAAGA GGGATAAACG 181 AAATA chromosome segregation protein promoter (natural) SEQ ID NO: 23 1 GAAGTACAAA GTTACTTTAA CTATAATGAA AAACAAGACA ATATAAAGAA AACAACATAT 61 AAGGTTCAGT TCATAACTGA TTAGATTTAT AATAAATATT GTAAATCGGA CAAAAATAAA 121 TTAATTTTCA ATTAATTCAA AAAAACCATA TTTTTTTCGT TTTGGCATAT TTGGATTTGC 181 TACACTAAAG ATGATCAAGA AAGGGGAAAA GATAATCTTC AATCTTGTGT ACTTAGTTTG 241 TTAATTAATT TATAAATTTA GGGAGGAAAC CTATC Chromosome Partition Protein Smc promoter (natural) SEQ ID NO: 24 1 GCAATGCACA AGATGCTGAA ACAAAGGCAC AACAAAATGC AGATCAAGCT TCACCAGCTA 61 ATATTCAAAA GGCACAAGAT GCTATTGCTA ATCAAGAAAC TCAAATTAGT AAAGACACCG 121 ATGCTATTAA TGACGCTAAC AAAGCCGTTA GCGATGCACA AAGCACAGTT GATGCAGCGC 181 AAAAAAAGTT AATGATGCAA CTACTGCTCG TGACAATCAA CAAAAGAATG TTGATACTGC 241 TAGTGATGCA GTTAAGAATG CTCAAGCTAT TCTTGACAAC AGTGATCAGG CTAAAAAGGA 301 AGCCCAAGAT GCT Lactobacillus reuteri 3630 F1 16S SEQ ID NO: 25 1 GCCGCGGGTG CCTATACATG CAGTCGTACG CACTGGCCCA ACTGATTGAT GGTGCTTGCA 61 CCTGATTGAC GATGGATCAC CAGTGAGTGG CGGACGGGTG AGTAACACGT AGGTAACCTG 121 CCCCGGAGCG GGGGATAACA TTTGGAAACA GATGCTAATA CCGCATAACA ACAAAAGCCA 181 CATGGCTTTT GTTTGAAAGA TGGCTTTGGC TATCACTCTG GGATGGACCT GCGGTGCATT 241 AGCTAGTTGG TAAGGTAACG GCTTACCAAG GCGATGATGC ATAGCCGAGT TGAGAGACTG 301 ATCGGCCACA ATGGAACTGA GACACGGTCC ATACTCCTAC GGGAGGCAGC AGTAGGGAAT 361 CTTCCACAAT GGGCGCAAGC CTGATGGAGC AACACCGCGT GAGTGAAGAA GGGTTTCGGC 421 TCGTAAAGCT CTGTTGTTGG AGAAGAACGT GCGTGAGAGT AACTGTTCAC GCAGTGACGG 481 TATCCAACCA GAAAGTCACG GCTAACTACG CCCCCCACCA GCCCCAA Lactobacillus reuteri 3632 F1 16S SEQ ID NO: 26 1 TGCTGGGGTT TGCCTATACA TGCAGTCGTA CGCACTGGCC CAACTGATTG ATGGTGCTTG 61 CACCTGATTG ACGATGGATC ACCAGTGAGT GGCGGACGGG TGAGTAACAC GTAGGTAACC 121 TGCCCCGGAG CGGGGGATAA CATTTGGAAA CAGATGCTAA TACCGCATAA CAACAAAAGC 181 CACATGGCTT TTGTTTGAAA GATGGCTTTG GCTATCACTC TGGGATGGAC CTGCGGTGCA 241 TTAGCTAGTT GGTAAGGTAA CGGCTTACCA AGGCGATGAT GCATAGCCGA GTTGAGAGAC 301 TGATCGGCCA CAATGGAACT GAGACACGGT CCATACTCCT ACGGGAGGCA GCAGTAGGGA 361 ATCTTCCACA ATGGGCGCAA GCCTGATGGA GCAACACCGC GTGAGTGAAG AAGGGTTTCG 421 GCTCGTAAAG CTCTGTTGTT GGAGAAGAAC GTGCGTGAGA GTAACTGTTC ACGCAGTGAC 481 GGTATCCAAC CAGAAAGTCA CGACTAACTA CGCCCCACAC CCCAGCCGCA A Lactobacillus reuteri 3630_00184 SEQ ID NO: 27 1 ATGGATATGA AAATAAAAAA AGAACCACCA CAACAAGTAA AATTAGTTGA AGTAATTCAG 61 GTTATAACCT CTCGTGGAGC TGGAACAAAG GAGGATCCGA TAAGAAAGAT TATTCAGTAT 121 TGGAGCAAAG AAGGCACATT ATTAGCAGAA AGTTTTGGAA ACTAA Lactobacillus reuteri 3630_00491 SEQ ID NO: 28 1 ATGGCTGGTA TCAAAAGTAT CGCAAAAGCG GTAATGACCC AGAATCACTT CGTGATCGCC 61 GAGGCAAAGC TAAGCCAGAA GAGAAGTGGA CGGAAGTTGA CCGACTCAAG GCAGAAAATC 121 GCTTATTAA Lactobacillus reuteri 3630_00497 SEQ ID NO: 29 1 ATGGCTAAAT ACACTGTTGA ATTAAGTGAA GAAGATATCC AAATGATCAA GGATTGTCAT 61 TCAAAGAATC CTTCTATCAT GAAGGCAATG AACGACGCTA AAAAAGTTGA AGATTAA Lactobacillusreuteri 3630_00533 SEQ ID NO: 30 1 GTGGATGCGG ATTCGCTGGC ACTCGTTGAT GCACTTTCAC TTGCGCTCGT TGATGCCGAT 61 TCACTGGCAC TCGTTGATGC ACTTTCGCTA GCACTAGTAG AAGCTGACTC ACTTGCACTT 121 GTCGATGCCG ATTCGCTTGC ACTTGTCGAT GCTGATTCGC TTGCGCTCGT TGAGGCTGAT 181 TCGCTAGCAC TAGTAGAAGC TGATTCACTG GCACTCGTTG AGGCACTTTC ACTTGCGCTT 241 GTTGAAGCCG ACTCACTTGC GCTCGTTGAT GCACTTTCGC TGGCACTTGT CGATGCCGAT 301 TCACTTACGC TCGTTGAGGC CGATTCGCTG ACACTCGTTG ATGCACTTTC ACTTACGCTC 361 GTTGAGGCCG ATTCGCTGAC ACTCGTTGAT GCACTTTCAC TTACGCTCGT TGAGGCCGAT 421 TCGCTGACAC TCGTTGATGC ACTTTCGCTG GCACTTGTCG AGGCACTTTC ACTTACGCTC 481 GTTGAGGCCG ATTCACTTAC GCTCGTTGAG GCCGATTCAC TTGCGCTTGT GGATGCGGAC 541 TCACTTGCAC TCGTTGAGGC ACTTTCACTT GCACTTGTCG ATGCAGATTC GCTGGCACTC 601 GTTGATGCAC TTTCACTTGC ACTCGTTGAT GCACTTTCAC TTGCACTTGT CGATGCGGAT 661 TCACTTGCAC TTGTTGAAGC GGATTCGCTA GCACTTGTCG ATGCGGATTC ACTTGCGCTT 721 GTTGAAGCGG ATTCGCTGGC GCTTGTTGAA GCCGACTCAC TTGCACTCGT TGAGGCTGAT 781 TCACTTGCAC TCGTTGAGGC ACTTTCGCTG GCGCTCGTTG ATGCAGATTC GCTGGCACTC 841 GTTGAGGCCG ATTCGCTGGC GCTTGTTGAG GCCGATTCGC TTGCACTTGT CGATGCTGAT 901 TCACTTGCAC TGGTTGAAGC AGATTCGCTG GCACTCGTTG AGGCACTTTC GCTGGCACTC 961 GTTGAGGCCG ATTCACTTGC GCTTGTTGAA GCTGATTCAC TTGCACTTGT CGATGCTGAT 1021 TCACTTGCGC TAGTAGATGC CGATTCGCTG GCACTCGTTG AAGCAGATTC ACTTGCGCTT 1081 GTTGAAGCCG ATTCACTTGC GCTTGTTGAA GCCGACTCAC TTGCACTCGT TGAGGCACTT 1141 TCGCTGGCGC TCGTTGAAGC AGATTCGCTG GCACTCGTTG AAGCAGATTC GCTGGCGCTT 1201 GTTGAGGCCG ATTCGCTTGC ACTTGTCGAT GCTGATTCAC TTGCACTGGT TGAAGCAGAT 1261 TCGCTGGCAC TCGTTGAGGC ACTTTCGCTG GCACTCGTTG AGGCCGATTC ACTTGCGCTT 1321 GTTGAAGCTG ATTCACTTGC ACTTGTCGAT GCTGATTCAC TTGCGCTAGT AGATGCCGAT 1381 TCGCTGGCAC TAGTAGAAGC AGATTCACTT GCGCTTGTTG AAGCCGATTC ACTTGCGCTT 1441 GTTGAAGCCG ACTCACTTGC ACTCGTTGAT GCCGATTCAC TTGCACTTGT GGATGCGGAC 1501 TCACTTGCAC TCGTTGATGC ACTTTCACTT GCACTTGTGG ATGCGGATTC GCTGGCACTC 1561 GTTGATGCAC TTTCACTTGC GCTCGTTGAT GCCGATTCAC TGGCACTCGT TGATGCACTT 1621 TCGCTAGCAC TAGTAGAAGC TGACTCACTT GCACTTGTCG ATGCCGATTC GCTTGCACTT 1681 GTCGATGCTG ATTCGCTTGC GCTCGTTGAG GCTGATTCGC TAGCACTAGT AGAAGCTGAT 1741 TCACTGGCAC TCGTTGAGGC ACTTTCACTT GCGCTTGTTG AAGCCGACTC ACTTGCGCTC 1801 GTTGATGCCG ATTCACTGGC ACTCGTTGAG GCACTTTCAC TTGCGCTTGT TGAAGCCGAC 1861 TCACTTGCGC TCGTTGATGC ACTTTCGCTG GCACTTGTCG ATGCCGATTC ACTTGCGCTT 1921 GTGGATGCGG ACTCACTTGC ACTCGTTGAA GCCGATTGGC TTGCACTAGT AGAAGCTGAT 1981 TCACTGGCGC TCGTTGAGGC TGATTCGCTG GCGCTCGTTG AGGCTGATTC ACTGGCACTC 2041 GTTGAGGCCG ATTCGCTGGC GCTCGTTGAT GCAGATTCGC TGGCACTAGT AGAAGCTGAT 2101 TCACTGGCGC TCGTTGATGC CGATTCACTT GCACTTGTCG ATGCGGACTC ACTTGCACTC
2161 GTTGATGCAC TTTCGCTTGC ACTTGTGGAT GCGGATTCGC TGGCACTCGT TGATGCACTT 2221 TCGCTAGCAC TTGTCGATGC CGATTCACTT GCACTCGTTG ATGCACTTTC GCTAGCACTC 2281 GTTGATGCAC TTTCACTTGC ACTTGTGGAT GCGGATTCGC TGGCACTTGT TGATGCGGAC 2341 TCACTTGCAC TTGTTGAAGC CGATTCACTG GCGCTCGTTG ATGCCGATTC ACTTGCACTT 2401 GTCGATGCCG ATTCACTGGC GCTTGTTGAT GCGGACTCAC TTGCACTCGT TGATGCACTT 2461 TCACTTGCAC TTGTGGATGC GGATTCGCTG GCACTAGTAG AAGCTGACTC ACTTGCACTT 2521 GTCGATGCCG ATTCACTGGC ACTCGTTGAA GCACTTTCAC TTGCGCTTGT TGATGCGGAC 2581 TCACTTGCAC TCGTTGAAGC CGATTCGCTA GCACTTGTCG AAGCTGATTC ACTGGCGCTC 2641 GTTGATGCTG ATTCACTGGC GCTTGTTGAA GCCGACTCAC TTGCGCTCGT TGATGCACTT 2701 TCACTTGCGC TCGTTGATGC CGATTCACTA GCACTAGTAG AAGCTGATTC ACTGGCGCTT 2761 GTTGATGCAG ATTCGCTGGC ACTTGTCGAT GCCGATTCGC TAGCACTAGT AGAAGCTGAT 2821 TCACTGGCGC TTGTTGATGC AGATTCGCTG GCACTTGTCG ATGCCGATTC GCTAGCACTA 2881 GTAGAAGCTG ATTCACTTGC ACTTGTCGAT GCCGATTCAC TGGCGCTCGT TGATGCCGAT 2941 TCGCTGGCAC TAGTAGAAGC TGACTCACTT GCACTTGTCG ATGCCGATTC ACTGGCACTC 3001 GTTGATGCAC TTTCGCTAGC ACTTGTAGAT GCGGATTCAC TTGCACTCGT TGATGCACTT 3061 TCACTGGCAC TCGTTGATGC ACTTTCGCTA GCACTCGTTG AAGCACTTTC ACTTGCGCTT 3121 GTTGATGCGG ATTCGCTGGC ACTCGTTGAT GCACTTTCAC TTGCGCTCGT TGATGCCGAT 3181 TCACTTGCGC TTGTGGATGC GGACTCACTT GCACTCGTTG ATGCACTTTC GCTTGCACTT 3241 GTGGATGCGG ATTCGCTGGC ACTAGTAGAA GCAGATTCAC TTGCGCTCGT TGATGCCGAT 3301 TCACTTGCGC TTGTGGATGC GGACTCACTT GCACTCGTTG ATGCACTTTC ACTTGCACTT 3361 GTGGATGCGG ATTCGCTGGC ACTAGTAGAA GCTGACTCAC TTGCACTCGT TGAAGCACTT 3421 TCACTTGCGC TTGTGGATGC GGACTCACTT GCACTTGTCG ATGCTGATTC GCTAGCACTA 3481 GTAGAAGCTG ATTCACTTGC ACTCGTTGAT GCACTTTCAC TTGCGCTTGT TGAAGCCGAC 3541 TCACTTGCGC TCGTTGATGC CGATTCACTT GCACTCGTTG AGGCACTTTC ACTTGCGCTT 3601 GTTGAAGCCG ACTCACTTGC GCTCGTTGAT GCACTTTCGC TGGCACTTGT CGATGCCGAT 3661 TCGCTGGCAC TAGTAGATGC GGACTCACTT GCGCTCGTTG AAGCCGATTG GCTTGCACTA 3721 GTAGAAGCTG ATTCACTGGC GCTCGTTGAG GCTGATTCAC TGGTACTCGT TGATGCACTT 3781 TCGCTAGCAC TCGTTGAAGC ACTTTCACTT GCGCTTGTGG ATGCGGACTC ACTTGCACTA 3841 GTAGAAGCAG ATTCACTTGC GCTCGTTGAT GCCGATTCAC TTGCACTTGT CGATGCCGAT 3901 TCACTTGCGC TTGTGGATGC GGACTCACTT GCACTCGTTG ATGCACTTTC GCTTGCACTT 3961 GTGGATGCGG ATTCGCTGGC ACTAGTAGAA GCAGATTCAC TGGCGCTCGT TGATGCCGAT 4021 TCACTTGCAC TTGTCGATGC CGATTCACTT GCACTCGTTG ATGCACTTTC ACTGGCACTC 4081 GTTGATGCAC TTTCGCTAGC ACTCGTTGAA GCACTTTCAC TTGCGCTTGT TGATGCGGAC 4141 TCACTTGCAC TTGTTGAAGC CGATTCACTG GCGCTCGTTG ATGCACTTTC ACTTGTGCTT 4201 GTTGAAGCCG ACTCACTTGC GCTCGTTGAT GCACTTTCAC TTGCGCTCGT TGATGCCGAT 4261 TCACTAGCAC TAGTAGAAGC TGATTCACTG GCGCTTGTTG ATGCCGATTC GCTGGCACTT 4321 GTCGATGCCG ATTCGCTAGC ACTAGTAGAA GCTGATTCAC TGGCACTTGT CGATGCCGAT 4381 TCACTGGCGC TCGTTGATGC CGATTCGCTG GCACTAGTAG AAGCTGACTC ACTTGCACTT 4441 GTCGATGCCG ATTCACTGGC ACTCGTTGAT GCACTTTCGC TAGCACTCGT TGATGCACTT 4501 TCGCTAGCAC TCGTTGATGC ACTTTCACTT GCGCTCGTTG ATGCAGATTC GCTAGCACTA 4561 GTAGAAGCTG ACTCACTTGC ACTTGTCGAT GCCGATTCAC TGGCACTCGT TGATGCACTT 4621 TCGCTAGCAC TCGTTGATGC ACTTTCACTT GCGCTTGTTG AAGCCGACTC ACTTGCGCTC 4681 GTTGATGCAG ATTCGCTAGC ACTAGTAGAA GCAGATTCAC TTGCGCTCGT TGATGCCGAT 4741 TCACTTGCGC TTGTGGATGC GGACTCACTT GCACTCGTTG ATGCACTTTC ACTTGCACTT 4801 GTGGATGCGG ATTCGCTGGC ACTAGTAGAA GCTGACTCAC TTGCACTCGT TGAAGCACTT 4861 TCACTTGCGC TTGTGGATGC GGACTCACTT GCACTTGTCG ATGCTGATTC GCTAGCACTA 4921 GTAGAAGCTG ATTCACTTGC ACTCGTTGAT GCACTTTCAC TTGCGCTTGT TGAAGCCGAC 4981 TCACTTGCGC TCGTTGATGC CGATTCACTT GCACTCGTTG AGGCACTTTC ACTTGCGCTT 5041 GTTGAAGCCG ACTCACTTGC GCTCGTTGAT GCACTTTCGC TGGCACTTGT CGATGCCGAT 5101 TCGCTGGCAC TAGTAGATGC GGACTCACTT GCGCTCGTTG AAGCCGATTG GCTTGCACTA 5161 GTAGAAGCTG ATTCACTGGC GCTCGTTGAG GCTGATTCAC TGGTACTCGT TGATGCACTT 5221 TCGCTAGCAC TCGTTGAAGC ACTTTCACTT GCGCTTGTGG ATGCGGACTC ACTTGCACTA 5281 GTAGAAGCAG ATTCACTTGC GCTCGTTGAT GCCGATTCAC TTGCACTTGT CGATGCCGAT 5341 TCACTTGCGC TTGTGGATGC GGACTCACTT GCACTCGTTG ATGCACTTTC GCTTGCACTT 5401 GTGGATGCGG ATTCGCTGGC ACTAGTAGAA GCAGATTCAC TTGCGCTCGT TGATGCCGAT 5461 TCACTTGCAC TTGTCGATGC CGATTCACTT GCACTTGTTG AAGCAGATTC ACTTGCGCTC 5521 GTTGAGGCCG ATTCGCTGGC ACTCGTTGAT GCCGATTCGC TAGCACTAGT AGAAGCTGAT 5581 TCACTTGCGC TCGTTGATGC CGATTCACTT GCACTTGTCG ATGCCGATTC ACTGGCGCTT 5641 GTGGATGCGG ACTCACTTGC ACTCGTTGAT GCACTTTCAC TTGCACTTGT GGATGCGGAT 5701 TCGCTGGCAC TTGTCGATGC CGATTCACTG GCGCTTGTTG ATGCGGACTC ACTTGCACTC 5761 GTTGATGCAC TTTCACTTGC ACTTGTGGAT GCGGATTCGC TGGCACTAGT AGAAGCTGAC 5821 TCACTTGCAC TTGTTGAAGC CGATTCACTG GCGCTCGTTG ATGCACTTTC ACTTGTGCTT 5881 GTTGAAGCCG ACTCACTTGC GCTCGTTGAT GCACTTTCAC TTGCGCTCGT TGATGCCGAT 5941 TCACTAGCAC TAGTAGAAGC TGATTCACTG GCGCTTGTTG ATGCAGATTC GCTGGCACTT 6001 GTCGATGCCG ATTCGCTAGC ACTAGTAGAA GCTGATTCAC TTGCGCTCGT TGATGCCGAT 6061 TCGCTAGCAC TTGTCGAAGC TGATTCACTG GCACTCGTTG ATGCACTTTC ACTTGCACTC 6121 GTTGATGCCG ATTCGCTAGC ACTTGTCGAA GCTGATTCAC TTGCGCTCGT TGATGCTGAT 6181 TCACTGGCGC TTGTTGAAGC CGACTCACTT GCGCTCGTTG ATGCACTTTC ACTTGCGCTC 6241 GTTGATGCCG ATTCACTAGC ACTAGTAGAA GCTGATTCAC TGGCGCTTGT CGATGCCGAT 6301 TCGCTAGCAC TTGTCGAAGC TGATTCACTT GCACTCGTTG ATGCTGATTC ACTTGCACTT 6361 GTCGATGCTG ATTCACTTGC GCTCGTTGAT GCTGATTCGC TGGCACTTGT CGATGCCGAT 6421 TCACTTGCGC TTGTTGAAGC TGATTCACTT GCGCTTGTTG ATGCGGATTC GCTTGCACTC 6481 GTTGATGCAC TTTCACTTGC GCTCGTTGAT GCCGATTCGC TGGCGCTCGT TGATGCACTT 6541 TCACTTACGC TCGTTGATGC ACTTTCACTT ACGCTCGTTG ATGCACTTTC ACTTACGCTC 6601 GTTGATGCAC TTTCACTTAC GCTCGTTGAT GCACTTTCAC TTACGCTTTT TGATGCCGAT 6661 TCGCTGGCAC TCCTCGTTGA AGCGGATTCG CTGGCACTCC TCGTTGAAGC GGATTCACTT 6721 ACGCTCGTTG ATGCGCTAGT CGAAGTACTC GTCGAGGTGG ATTCCTGTTC ACTCTTACTC 6781 GTCAATTGA Lactobacillus reuteri 3630_00804 SEQ ID NO: 31 1 ATGGAGATAT TGGTAACGTT ATTTGATTTG GTGTTTTTTA TTACGTTTAT AGTCGCAATT 61 GTCTATGGTA TTAGGTGGTT TAAAGGAAGA AAAGATAAAG AAAATGAATC TCTTAAGAAA 121 CGCCGTTTGT AA Lactobacillus reuteri 3630_00827 SEQ ID NO: 32 1 ATGATTAACT TAAACTTAGC AGGCTTAGAT TTTGTAATGA CGGCACTTTT TATTGTGTTG 61 TTTACAGAAC AGTTGAAAAA TGCCCGAACT CAGCGTGATG CTCTGATTGG TTTAGCATTT 121 GCAATTATTT GTTTACTATT TTGCAACAAG AATGTTTTTC TATTAGTGAC ATTAGTAACA 181 CTTGTCGCAC TGTTTTCATT AAATTACTTA ATCACGAGGA GAAAAAATGA CATTAACTGA Lactobacillus reuteri 3630_00947 SEQ ID NO: 33 1 ATGTCAGAGA TGAAAAATCG CGTAATTAAT TTTCGGAATG ATAACTTAGC CAAACTTATA 61 GTCAATTATT ATGGAAATAG TCAATTAAGT GTGCATATTA CTAATAATAT GTTTTTTGAA 121 TGA Lactobacillus reuteri 3630_01261 SEQ ID NO: 34 1 ATGAAACGCA AAATTGCATT AGCTCAACTT GATATTCAAT TAGGAAATCC TGCCGAAAAT 61 TATCAAAAAG CTAAACAAGC GATTGAAGAA GCTGCTAGTC ACCATGCAGA TATCGTTGTC 121 TTGCCGGAGA TGTGGAATGC TGGCTATGCC TTAGATCAAT TAGCAGAATT GGCAGATGAA 181 AACGGTCAAA AGACACAAAA ATTTCTTAGT GAGTTAGCGT TAGAAAATCA AATTAACATT 241 GTCGGTGGTT CAGTAGCGGT GAGATGTGGA CAATCTTTTT TCAATACAAC CTATGTTTAT 301 GATCAAAAGG GAAATCTAAT TAGCAGTTAC GAGAAGGTGC ATTTATTTGG ACTAATGAAT 361 GAAGACCGAT ATCTAAAAGC CGGGCAAAAA GAAAATCACT TTGAATTAGC TGGGGTTCCG 421 AGTGCAAGTT TTATTTGTTA TGATTTGCGA TTCCCTGAAT GGATTAGAAC AGTCACTCGT 481 TATGGAACTG ATATCTTATA TTTTTCGGCA GAATGGCCAA GCAAACGGAT TAAACAATGG 541 AAAATAATGC TTCAGTCACG GGCAATTGAA AATCAAGCCT TTGTAGTCGC GGTCAATCGT 601 GTTGGGACGG ATTTAGAGAA TAGCTTTAAT GGTCATTCGT TAGTAATAGA TCCGCTTGGG 661 CAGATTATCC ATGATGCAGG AGAAGTTGAA CAAGTAAGTT ATGCAGAAAT TGACTTAGCG 721 CAGTTAGCAC AGGTTCGGGG GCCGATTCCG GTGTTTAAGG ATCGCCGACC AAGTCTTTAT 781 CATTAA Lactobacillus reuteri 3630_01695 SEQ ID NO: 35 1 ATGCAAAATA AAGATGCTTG TACATCAATT ATGGTCGGTA AAAAGGCTTC TCTCGACGGT 61 GCTAATTATA TTGCTCGTAA TGAAGATCGC GTAAAAGCAA TTGAACCCAA GCGATTTTTA 121 GTAAAACCGG CAGTAAAAGG ACGCCACGAA ACCTACGTAT CACCTTACAA TAAAGTAACT 181 GTAGCTTTGC CGGAAGAGAG AATGCGTTAT ACTTCTACGC CTACCCTTGA TCAAACAGCC 241 GGACCTAATG AAGAAGATGG AATTAATGAA GCAAATGTGG CAGCTTCCTT TACTGAGAGT 301 GTTTATGCAA ATGATCGGGT GTTAGCATAT GATCCATACG TAAAAAATGG CCTGGCAGAA 361 GACTCACTTT GTACTTTAGT ATTACCGTAT ATTCATTCTG CCCGTGAAGG AGTTGAATAT 421 ACTGGAAAAT TAATTGCTGA ATTGGGCTCT GCTGAGGGAA ATGGAATGCA ATTTGCAGAT 481 GCAGATGATA TTTGGTATAT GTAA Lactobacillus reuteri 3630_01889 SEQ ID NO: 36 1 ATGAATTATT TTATCGGTGT TGATGTTGGA ACTACTTCTA CAAAGGCAGT TCTATATGAC 61 CAAAATGCAA CTGTGTTAGA TCAATTTAGC CAAGGTTATT CCCTTTACCG CGATGCTAGT 121 GGAATGGCTG AACAAAACCC AACTGCAATT GTCGAAGCAG TCGAAAAAGT TATTCATGAT 181 GCAGCACAAA AAGCAGATTT AACAAATGGA AAATTGTTAG CGGTATCATT TTCTAGTGCT 241 AACCAAAGTG TGATTATGCT CGACAAGAAT TTCAATCCCC TTTCACGGGT CATCACTTGG 301 GCTGATACCC GTGCACGTGA TGTCGCCAAC GAATTAAAGA ATAGTCCTGC TGGTCAGCAA 361 ATCTATGCTA AAACAGGTAC ACCTATTCAT CCAATGTCCC CATTGACCAA GATTATGTGG 421 CTCAATAAGA CACAAGCAGA TAAGGTTGCT CAAACTGCAT ATTTTGGCGA TATCAAATCC 481 TACCTCTTCC ACCAGTTTTT CAATACATTT AAGGTTGATG TTTCCATCGC TTCATGTACC
541 GGAATGATGA ATGTCAATAC GTGTGACTGG GACGATCAAG CATTGGAACT CGCTAACGTC 601 GACTGTTCCC AATTACCAGA AATCGTGAAC GGAACAACCC AAGCGATTGG CCTAACAGCA 661 GCGGCGCAAG CAAAAATGGG TATCCCCGCT GACACGCCAT TTGTCTATGG TGCCTTTGAC 721 GGTGCTTTAT CTAATTTAGG TGTGGGGGCA ATTAAGCAAA ATACTGTTGC CATTACGATT 781 GGAACTTCGG CTGGTGTTCG GGTAGTAACT GACCATCCAG TGATCGATCC TCAGCAACGA 841 CTCTTCTGTT ACGCCGTGGA TAAAGGTTTA TGGGTCATCG GCGGTCCGCT TAATAATGGT 901 GGCGATGTCT ATCAGTGGGC CGTTGAACAC TTAGTTGACG CTAGTGCAGT TAAAAATGAA 961 AATATTGATC CCTACACTCT TGCTAACCGA GTTATTGAAG GTGTTCCCGC CGGAGCTCAC 1021 GGTTTGCTCT TCCACCCATT CCTTGGCGGT GAACGGGCAC CATTATGGGA CGCTAATGCG 1081 CGCGGTAGTT TCTTTGGACT TTCCCACATT CATACTCGTG CCGATATGCT GCGCTCAGTA 1141 ATGGAAGGAA TTTGTATGAA TATTGCAACT GTTTTCCAAG CGGTTCGTGA TCTTGTTGGT 1201 AATCCTGCAA GCGTAACTGC AACTGGCGGT TTTGCGCGAG CTGAAGTTTG GCGGCAAATG 1261 TTAGCAGATG TCTTGAACTG TCCGGTCAAT ATCCCGAACT CATTTGAATC TGGTTGTCTC 1321 GGTGCAATCA CCATGGCAAT GAAGAGTTTA GGAATGATTG AAAACTATGA AATCATTAAA 1381 ACATTAGTTG GTGATATCAG TTCTTATCAG CCAAATCAAG ATGCGGTTAA TGTTTATCAA 1441 AATTACTTAC CACTTTTTAA GCAGGTCGAA GGATTATTAA CACCAGCCTA TTCGACCATC 1501 GCTAAATTAC AACAACAATC TACTACTCAT TAG Lactobacillus reuteri 3630_01932 SEQ ID NO: 37 1 ATGACAACAT CAATGATCCA CAGTAGAAGT ATGTTGGCGA AAGTGATTGC AGAATCACCT 61 TCACCTTTTA TTATACCAAT TTTTTGTCCT AATGTAATAA AGATTATCTT TTTATCTATA 121 AATTATTTTA TGAAAAGAGT GGAAAAGGCA AGAAGAGCAA TCAAAAAGCC AATTTTAACA 181 ATTTTATTAA GTTGA Lactobacillus reuteri 3630_02243 SEQ ID NO: 38 1 ATGAGCAAAC TATTACTTGA TGAAAGACCG TTACAAGTTC AGGCATCGTT AGCTGGAGCG 61 TTGAAAAGCT TAGACGAAGC TGTTATTCTC CAGCAGCTTC ACTATTGGCT TCAACGTTCT 121 AATACAGTAA GAGACAATCA CAAATGGGTC TATAACAGCA TGGCTGATTG GAATAAACAG 181 TTCCCTTGGC TTTCTAGAAA GGCTCTATCG AACCACTTTA AGAAATTAGA AAAACGAGGA 241 CTAATTATTA CAGGCAACTA TAATAAATTA TCTTTTGACA AAACAAAGTG GTATCGAATT 301 GACTATGACG CATTTTCCCA TTTGGAACAA CGATTGGGTA GAAACTACCC AACGAATGGG 361 AAGAATCTAC CCAATGGAGA CGGTAAAAAC TGCCCAATCG GAGAGGAAGA ATCTACCCAA 421 CCAATACCAA TAGACTACCA AGAGACTACA CAAAAGACTA CTACAAGAGA TAAAGGGCAG 481 GCACAGCCAG CCCAACCTTC CATTGCTGCA CAGCGGCGAG AAGTTGTTGA ATATCTCAAT 541 CAAAAAAACT GGCAAGCACT TCAAGCCTGA Lactobacillus reuteri 3630_02365 SEQ ID NO: 39 1 TTGAATAATT TTCAAAAGGC AATTTTCTTG TTGCAGAATA TCGACAAGCT TAAACAGCTT 61 AATGGTAAAG CGATGACTCT TACTGAGTTC TCTAAAATAA CTGATGTTTC ACGGCCAACG 121 TTGTATAAAT ACATTCAGCA TCCAGAAACA ATGAGTAGTT CGTTTGTAAA TAAAGCGGCC 181 ATGCTCTACG ACAAGGTTGT TAAATTTCAA GATATTCTTG ATACAGTTCA GCGTGAAGAT 241 AAACAATTTA AGACTACCAG GCAGGAATTG ATTAAGCTTT TAGAGTCTAA TGTAGCTAAT 301 ATTGAAGTTA CAGATTATAC AAAAGCAATC GCGACAGTAA TTATTAGTGA CTTAAAAGAA 361 GAAAATTCAA GTCTGCTAAA AGCGTTAAGT AAGCAATTAC CATTTAAACC AAATTTAAAT 421 GATAATTTGT CAAAATAG Lactobacillus reuteri 3630_02435 SEQ ID NO: 40 1 GTGAAGATGA ATAGTATGAC AAACAACCAA AAAGAAAGTT GGAACGTTGG CAACTATAAA 61 ATCAATGTAT TACCAGATGA TGAGTTCCAG CAATTGTTAA AGAACCAACG CCAACTTCAA 121 CAGATCATTG AAAGTATGCC ACTACCAACC GACCCCAATG TTGATCTAGT TAAAAAGATT 181 CATTCCCAAC TCCCTATTAC AAACTGGGCT TGGGAATTAA CTAAACAACG AGAACATGAG 241 GAAAAGTTAA AGAAACAAAA GCAGCGAATT GCACAGCAAT CGCTTAACTA TCCAACAAAC 301 CTCAAGAAAC CGGATAATGG CCTTTCCCTA TAA Lactobacillus reuteri 3630_02436 SEQ ID NO: 41 1 ATGAATTCTA ATTTGAAAAA GAATTTGATT ATCGCAAATG GATTTCTACT ACTAATAATA 61 ATATTTTATG TTTTATTACA TATGGGTCCA TTAAATATGA AAGTCTTATT AGTAGGATTG 121 GTATTAATGA ATCTGACAGT AATATTTAAA TAA Lactobacillus reuteri 3630_02437 SEQ ID NO: 42 1 ATGGATAAAT TAACATTGAA AAAACTAATT ATTATTACAT TAGGCATGCT AATGGTATTT 61 CTTTTAGGTA TGCACCTTCA TCAAAAGACA CACTTTAACA AAAACGTGAA GATTAATAAT 121 ATTCCAGTCG GAGGTCTTAC TGTTCAACAG GCATATAATA AAGTAAGTAA TACTAAAAGA 181 AAATCAAAAA TCTACATTAA CAAAAAGTTA GTTTATTCAG GTAAAAGTAC TGACTCAGGT 241 TTTAAGTTAT CTGATAAAGA AAGATTTAGT AAGGCGTTAC ATTACCAATA CACTTTTTTT 301 CCCTCACGAA AACATGAAAA TTTGCTAGTT GAGCCAGCTG ATTTAGATAA GTCAGCGTTA 361 AATAATATTG ATTCGGCAAT AGTAGCTAGG ATTCATCAGC TCAATATAGG CAGAAAGGCC 421 CCACGTGATG CATACGCCGT TTACCAGAAT AATAAAGTTT CAGTTATTCC AGCAATTGAT 481 GGGACACGAT ATAGTGAACA AGGACTTTGT AATATTGCTA ATAAGGAATT TGTTAATGGG 541 ACAATTCATT TAACTCCTAA GGTTATTACT CCTTTATCGG CAAACAGTAA AGTAGTTCAA 601 GATGAAAAGA AACACCTGAG TAAACTACAA AATCGATCGG TTGTTTATCA GGTTCAGAAA 661 ACAAAATATA ATTTTAAAGC GTCTAATGTC ATTTCTAAAG CAACTTATCA GCATGGGAAA 721 TACCATTTTG AAACTGACAA CGTTAAATCC AAGATTGCCA ATATAAATAA TAAGCAAGCA 781 ACATTAGGAA AGAGCTTTAA ATTTAGAACT GATTCTGGAA AAGTTATTTC TACATCTAAT 841 CAGGGAACAT ATGGTTGGAA AATAAGTAGC AAGCAGGCAG GACAAACACT CTCTAAAGCG 901 TTAGCTAATA ATGTTAAGAG CGTTAATGCC GAAAATGATA TTTACGGTAA AGGCTATAGT 961 CATCTTGGTA CTGGATATTC GGCTGTGAAT AATCATGGGC TTGGTAATAC TTATGTGGCT 1021 GTATCATTAG CTAAACAGCA TGCTTGGTTT TATAAAAATG GAAAATGTGT ACTGAGTACA 1081 GATATTGTTA GTGGATCAGA TGACGCTAAT AATAGGACTC CTAAAGGTGT TTGGTATATC 1141 ATGTATCAAC AAACGCCATC AGTTTTACGT GGGACTAATG ATGATGGTTC CAAGTATAGT 1201 AGTCCTGTTC AGTATTGGTC TCCGTTTACT TTATCAGGGT GTGGCTTTCA TGATGCTAGT 1261 TGGAGGCATA ATTGGTCTAA AACAGCTTAT AAACAGACTC ATGGTGGCTC ACATGGCTGT 1321 ATTAACATGC ATCCGGAAAA TGCAGGAGAC GGTTTCCATG CCCTTACTAA AGGAGAACCG 1381 GTAATAATTT ATTAG Lactobacillus reuteri 3630_02438 SEQ ID NO: 43 1 ATGCAATTAA ACCATAAATT AGGAGTTTTC TTGGCAGCGC CATTTGCTCT ACTGGTTTTA 61 TCAGCTACAA ACGTGCATGC CGATAACATT CAAAGTAATA GTAACCAGAC AATCAGTAAT 121 ATGAGTTTGC AAACTAATGA CACAAAGACT CAACAAAATG TTGTAATGTC AAACGATGCA 181 AAAGCTCAAA TTACTGTAAA TCCTAGTTCT AATGCTAATT CTAGTTCTGT AGCAAAGATA 241 AATGAAAAGA ATAATGTAAA ATCGGATACT GACAATACTA ATGTCGAATC AAATGCTGAT 301 AATATTGGGA ACATTGCTTC TAGCGATTCC ACGGCAGTGG CTAATTCTGC TAGTTCCGAT 361 AATATTCAGT CATTTAACGT AAATACGCAG GAACAGCCTG CAATAAATGT ATCTGAACTA 421 ACAACCGAAG AGTATGTTAC GAATTACACT CAACAACAGA TCAATAATGC GACGACTATT 481 CATGATTACT TTATAAATCA AGGATGGACA CCAAATGCTA TTGCTGGAAT GCTTGGTAAC 541 TTTGTTTCAG AGTCAGGTTT AATCCCAGAC TTACATCAAT ATGGTGGTGG GCCTGGTTAT 601 GGGTTAGCTC AATGGCCATT TAATAGTGTA GTAAATTGGT GTCGTAATAA TGGATATGAT 661 TATCGTACTT TGCAAGGACA ATGTGCATAT ATTGAATATC AAATGACTCA TGGACAGCAG 721 TATTATCCAT CAGCTTACTC TAGAATGACC GCTAATGAAT ATATGCATAG TTATGCTTCA 781 GCATATACTT TAGGTATGAT TTGGCTTAAT AACTTTGAGC GACCTGCAAA TAGGAATCAG 841 CCAGCTCGTG GTCAACAGGC TCAATACTGG TATCAGTATT TCCAAAGTCA TGGTTCTACA 901 TCAGCACCGG TACAACAAAA TCCTAGTACA CCAGCAACAA CTCCTAGCTC AAGTCGAATG 961 AGTCAACACG GGACATTCAA AGTTGCTTAT GGATTAAATG TACGCCAAGC ACCAAGTACA 1021 TCGGCAGCTA TTGTAACGTA TTACAATGGT GGTCAAAGCT TTACATATGA TTCAAAGATT 1081 GAAGCTAACG GGTATCTTTG GGTATCATAC ATGAGTTATA GTGGCGTACG TCGTTATGTT 1141 GCAATTAAGA ATTTGAATAA TGGAACGACT TACGGTTATG ATTCGAATAA CTTCTCATAC 1201 AGTGCTCCTG CATCTTCAAC ACCATCTACT AATGTGCCAA GTACGCCAGC ACCAAGTACA 1261 TCTACTTCAT CAACTGAGAA GCAATATGGA ACATTCAAAG TTGCTTATGG ATTAAATGTA 1321 CGCCAAGCAC CAAGTACATC GGCAGCTATT GTAACGTATT ACAATGGTGG TCAAAGCTTT 1381 ACATATGATT CAAAGATTGA AGCTAATGGG TATCTTTGGG TATCATACAT GAGTTATAGT 1441 GGCGTACGTC GTTATGTTGC GATTAAGAAT TTGAGTAATG GAACAACTTA CGGTTACGAT 1501 TCAAATAACT TTTCATTTAA TGGGACTCCA GTAACATCAA ATAATAATCC TTCTAGTACT 1561 CCGGCAGTTC CGCAAGGTAA TAAGGGCCAA CAAGTTGTTG CTCTTGCACG TCAACAAATA 1621 GGTAAACCTT ATGTTTGGGG AGCAACCGGT CCTAATTCGT TTGATTGTTC AGGACTCGTG 1681 CAGTATGTTT ATCGTCAAGT TGGTGTTAAC TTACCACGGA CTACAACTCA ACAAGAATAT 1741 TGTGGACATG CTGTAAGCTT TAATAATCTT CAACCTGGAG ATCTAATGTT CTGGGGAAAG 1801 TATGGTAGTG CATATCACGT TGGAATCTAT ACCGGAAACG GTAATGTTTT ATTTGCACCG 1861 CAACCTGGTC AAACAGTTAA GGAACAACCA ATGCGCTATT ACATGCCTGC CTTTGCAAGA 1921 AGAGTATTGT AA
[0069] The present disclosure may be better understood with reference to the examples, set forth below. The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, and/or methods claimed herein are made and evaluated, and are intended to be purely exemplary and are not intended to limit the disclosure.
Example 1. L. reuteri Strain Identification
[0070] Seven Lactobacillus reuteri (L. reuteri) strains were isolated from older birds at the Research Center, Hannover from the cecal contents received from the Poultry Clinic, University of Hannover. All the seven strains are identified to be L. reuteri by 16S rRNA sequencing.
[0071] While only limited growth is observed for most strains under aerobic conditions in MRS broth and agar (de Man, J. D.; Rogosa, M.; and Sharpe, M. E. "A Medium for the Cultivation of Lactobacilli". J Appl Bact. 23: 130-135 (1960)), all isolates show very good growth on MRS agar and MRS broth under anaerobic conditions at 39.degree. C. Culturing the bacterial strains on blood agar under anaerobic conditions results mostly in limited growth. None of the strains is able to grow in Mueller Hinton broth under anaerobic conditions. For all further analysis, bacterial strains are grown in MRS medium under anaerobic conditions at 39.degree. C.
[0072] Antimicrobial susceptibility of bacterial isolates were tested using the AVIPRO.RTM. PLATE. All strains are resistant against colistin, doxycycline, enrofloxacin, erythromycin, neomycin, oxacillin, penicillin G, trimethroprim-sulfamethoxazole, tetracycline, tilmicosin and tylosin. All strains are resistant to streptomycin except strain 3632, and to tiamulin except strain 2098. In addition, resistance to cefpodaxime-proxetil is observed with strains 2091, 2095, 2097 and 3630; resistance to cefotaxime is observed with strains 2091, 2095 and 2097; and resistance to lincomycin is observed with strains 3630 and 3632. No strain was found to be resistant against amoxicillin, ceftiofur, erythromycin D, lincomycin-spectinomycin, and rifampicin under tested concentrations.
Example 2. L. reuteri Strain Selection and Anti-Infective Activity
[0073] To select the best strain for further use as a priobiotic, the L. reuteri isolates were tested for various desirable probiotic anti-infective properties, such as growth kinetics, ability to produce hydrogen peroxide, autoaggregation, enzyme profile, survival in the presence of ox bile and pancreatic enzymes, and sensitivity to heat shock and pH changes. The L. reuteri strains are also tested for safety using a haemolytic assay.
[0074] In general, all strains behave very similar in terms of probiotic properties, including growth kinetics and ability to produce hydrogen peroxide, except for strain 3632, which shows some unique properties, including the ability to autoaggregate in liquid media (comparable to that of the well-characterized human probiotic strain L. reuteri ATCC 23272). In addition to autoaggregation, L. reuteri 3632 also appears to produce an orange pigment, which resembles beta carotene in color. None of the other strains, including the human L. reuteri strain ATCC 23272 and L. acidophilus, produced orange colored pigment. None of the strains is found to be hemolytic on blood agar plates, suggesting that these isolates are less likely to be pathogenic to humans.
[0075] Whole-genome sequencing was performed for L. reuteri strains 2091, 3632, 3630, and an independently isolated L. reuteri strain 170331 of European origin, using PACBIO.RTM. sequencing (Amplicon Express). Sequencing, assembly and annotation statistics are summarized in TABLE 1. Genomic structures and organization differs among the tested strains.
TABLE-US-00002 TABLE 1 Strain 170331 2091 3632 3630 Genome size 2,090,596 bp 2,231,245 bp 2,482,713 bp 2,399,045 bp Contigs 9 11 7 5 Coding 2,154 2,280 2,595 2,467 Sequences (ORFs) Ribosomal 2,231 2.354 2,680 2,467 Binding Sites Transcription 1,123 1,123 1,375 1,339 Terminators Operons 452 472 541 475 tRNA 75 61 77 73 rRNA 18 19 13 18 Other RNAs 39 99 89 N/A CRISPR 1 0 0 0 Prophages 7 1 8 5 Islands 30 22 24 9 Bacteriocins 0 1 4 3
Example 2.5. Colonization of L. reuteri 3632 in 16-Day Old Embryos
[0076] The goal of this study was to test if L. reuteri 3632 colonizes the intestine of 16-day old embryos. To this end, 16 day-old embryos were obtained from Charles River and inoculated with 10{circumflex over ( )}8 CFU/embryo of L. reuteri 3632 by air cell, yolk sac and allantoic routes. Embryos were sacrificed on 18 days and the intestines were harvested and plated on MRS agar plates. An uninoculated group was included as a control. L. reuteri was recovered from the intestines of the majority of the embryos, suggesting that L. reuteri 3632 colonizes the intestine of 16-day old embryos. L. reuteri 3632 was not recovered from any of the control (uninoculated) embryos, even after 2-days of enrichment in liquid culture.
Example 3. Co-Culture of L. reuteri and C. perfringens in Brain Heart Infusion (BHI) Broth
[0077] L. reuteri and C. perfringens were cultured in BHI broth. CFU counts were determined 24 hours after coculture in BHI broth. L. reuteri were enumerated on MRS agar plates and C. perfringens was enumerated on OPSP plates. This data is from one representative experiment of 3 replicates. Co-culture-L. reuteri, L. reuteri recovered from co-cultured sample using L. reuteri-specific media. Co-culture-C. perfringens, C. perfringens recovered from co-culture sample using C. perfringens-specific media. See FIG. 9.
Example 4. In Vivo Effects of L. reuteri
[0078] Birds were vaccinated with CocciVac on day 0 and fed with L. reuteri in feed from day 0 to day 42 @ 10{circumflex over ( )}7 CFUs/Kg of feed. A separate group of birds were fed with feed supplemented with bacitracin methylene disalicylate (BMD_55).
[0079] Feed conversion ratio and European Broiler index were calculated. Birds that were fed L. reuteri demonstrated a reduction in feed conversion ratio and European Broiler index as compared to those fed BMD_55. See FIG. 8.
Example 4. The Effect of Prebiotics on the Growth of Lactobacillus reuteri
[0080] L. reuteri strains 3630 & 3632 were grown individually and in combination, in the presence of several different prebiotics, including fructooligosaccharides (FOS), arabinoxylan oligosaccharides (AXOS), mannan-oligosaccharides (MOS), or galacto-oligosaccharides (GOS).
[0081] As shown in FIG. 10, strains grown in the presence of GOS demonstrated increased growth as compared to strains grown in the presence of FOS, AXOS, or MOS.
Example 5. In Vivo Effects of L. reuteri
[0082] An identified strain can effectively function as a direct feed microbial only if the strain is able colonize the host gastrointestinal tract. The ability of L. reuteri strains to colonize chickens is assessed following different routes of administration.
[0083] L. reuteri is administered orally to 10-day old chicks. At various times post inoculation, chicks are sacrificed and the presence of L. reuteri is measured in the crop, small intestine, and cecum. Strain 3632 is able to colonize all three tissues and remain detectable for at least 18 days.
[0084] L. reuteri is administered by in ovo inoculation (i.e. injection into the egg) 3 days before hatching. Strain 3632 is found in the tissues of chicks at 3 and 7 days post hatching, while colonization of a control strain declines after day 3.
[0085] L. reuteri is administered in ovo by spraying a liquid containing bacteria onto the egg surface. Again, Strains 3630 and 3632 are able to colonize and remain present in chicks 3 and 7 days post hatching. Inoculation by spray is just as efficient as in ovo injection but requires less manipulation of the incubating egg.
[0086] Table 2 shows quantifies the effect of L. reuteri 3632 treatment on survival. The difference score between strain 3632 and the control is 3.3 and the difference between BMD and control is 2.5. Strain 3632 provides increased survival over BMD treated chics.
TABLE-US-00003 TABLE 2 Treatment conditions Difference Score Lr_3632 Ctrl 3.333333 BMD_55 Ctrl 2.5
Example 6. Necrotic Enteritis Model
[0087] L. Reuteri administered in ovo and in drinking water daily @ 10{circumflex over ( )}8 CFU/bird. The birds were orally gavaged with E. maxima on day 14. The birds were orally gavaged with C. perfringes on day 18, 19, and 20 with 10{circumflex over ( )}8 CFUs/bird.
TABLE-US-00004 TABLE 3 Summary of intestinal lesion score, total mortality percent (d15-d28), and necrotic enteritis mortality percent. Lesion Total NE No. Score Mortality Mortality Treatment Cages Mean (SE) Percent (SE) Percent (SE) T1. Unchallenged, 4 0.25.sup.a (0.25) 0.0.sup.a (3.4) 0.0.sup.a (2.5) untreated T2. E. maxima alone 4 0.50.sup.a (0.25) 4.2.sup.a (3.4) 0.0.sup.a (2.5) T3. E. maxima + C. 4 0.50.sup.a (0.25) 20.8.sup.b (3.4) 20.8.sup.b (2.5) perfringens T4. Lactobacillus 5 0.20.sup.a (0.22) 0.0.sup.a (3.0) 0.0.sup.a (2.3) reuteri alone (in ovo + oral) T5. E. maxima + L. 5 0.20.sup.a (0.22) 3.3.sup.a (3.4) 0.0.sup.a (2.3) reuteri (in ovo + oral) T6. E. maxima + C. 5 0.20.sup.a (0.22) 6.7.sup.a,b (3.0) 6.7.sup.a (2.3) perfringens + L. reuteri (in ovo + oral) T7. E. maxima + C. 1 0.0.sup.a (0.50) 16.7.sup.a,b (6.8) 16.7.sup.a,b (5.1) perfringens + L. reuteri (spray + oral) .sup..dagger.P-value 0.881 0.003 <0.001 .sup..dagger.Lesion scores and cage-level mortality percentages tested by one-way ANOVA. Within columns, means and percentages with a superscript in common do not differ with a level of significance of 5% over all comparisons.
Example 7. Global Metabolomics Analysis
[0088] A global metabolomics analysis of L. reuteri strains 3632 and 3630 were conducted. The strains were grown individually and in combination, and various molecules were analyzed in the cell pellet and the supernatant of the cultures. The strains were grown in AOF-MRS media control with no glucose but 0.5% GOS. The molecules in the supernatant represent molecules that are secreted by the cell.
[0089] Samples were subject to global untargeted metabolic profiling. Welch t-test and Principal Component Analysis (PCA) were used to analyze the data. Principal component analysis (PCA) is a mathematical procedure that reduces the dimensionality of the data while retaining most of the variation in a dataset. This approach allows visual assessment of the similarities and differences between samples. Populations that differ are expected to group separately and vice versa.
[0090] The data is shown in FIGS. 12-19.
EMBODIMENTS OF THE INVENTION
[0091] 1. A composition comprising at least one of: an isolated first Lactobacillus reuteri strain and an isolated second Lactobacillus reuteri strain;
[0092] wherein said composition increases animal health when an effective amount is administered to an animal, as compared to an animal not administered the composition.
[0093] 2. The composition according to embodiment 1, wherein the first Lactobacillus reuteri strain comprises at least one of:
[0094] a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO:26,
[0095] a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 1,
[0096] a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 3, and
[0097] a nucleic acid that encodes for an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 8;
[0098] wherein the isolated second Lactobacillus reuteri strain comprises at least one of:
[0099] a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO:25,
[0100] a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 27,
[0101] a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 28, and
[0102] a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 29.
[0103] 3. The composition according to any one of embodiments 1-2, wherein the isolated first Lactobacillus reuteri strain comprises a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 26.
[0104] 4. The composition according to any one of embodiments 1-3, wherein the isolated second Lactobacillus reuteri strain comprises a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 25.
[0105] 5. The composition according to any one of embodiments 1-4, wherein the composition comprises an isolated first Lactobacillus reuteri strain comprising a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 25; and a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO: 1,
[0106] 6. The composition according to any one of embodiments 1-5, wherein the isolated first Lactobacillus reuteri strain comprises a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO:26; and
[0107] wherein the isolated second Lactobacillus reuteri strain comprises a nucleic acid sequence having at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity with SEQ ID NO:25.
[0108] 7. The composition according to any one of embodiments 1-6, wherein at least one of the first lactobacillus strain and a second lactobacillus strain secrete at least one of cyclic dipeptides, short chain fatty acids, betaine, dimethylglycine, essential amino acids, nucleotides, myo-inositol, and indolin-2-one.
[0109] 8. The composition according to any one of embodiments 1-7, wherein the composition comprises a ratio of isolated first Lactobacillus reuteri strain to isolated second Lactobacillus reuteri strain of 0.75-1.5:1.
[0110] 9. The composition according to any one of embodiments 1-8, wherein the composition comprises about equal amounts of the isolated first Lactobacillus reuteri strain and the isolated second Lactobacillus reuteri strain.
[0111] 10. The composition according to any one of embodiments 1-9, wherein the composition is formulated as animal feed, feed additive, food ingredient, water additive, water-mixed additive, consumable solution, consumable spray additive, consumable solid, consumable gel, injection, or combinations thereof.
[0112] 11. The composition according to any one of embodiments 1-10, wherein the composition comprises animal feed.
[0113] 12. The composition according to embodiment 11, wherein the composition comprises the isolated first Lactobacillus reuteri strain in an amount of about 10{circumflex over ( )}2-10{circumflex over ( )}8 CFU/kg of the composition, about 10{circumflex over ( )}4-10{circumflex over ( )}7 CFU/kg of the composition, or about 10{circumflex over ( )}3-10{circumflex over ( )}5 CFU/kg of the composition.
[0114] 13. The composition according to any one of embodiments 10-12, wherein the composition comprises isolated second Lactobacillus reuteri strain in an amount of about 10{circumflex over ( )}2-10{circumflex over ( )}8 CFU/kg of the composition, about 10{circumflex over ( )}4-10{circumflex over ( )}7 CFU/kg of the composition, or about 10{circumflex over ( )}3-10{circumflex over ( )}5 CFU/kg of the composition.
[0115] 14. The composition according to any one of embodiments 10-13, wherein the composition comprises the isolated first Lactobacillus reuteri strain in an amount of about 10{circumflex over ( )}7 CFU/kg of the composition.
[0116] 15. The composition according to any one of embodiments 10-14, wherein the composition comprises isolated second Lactobacillus reuteri strain in an amount of about 10{circumflex over ( )}7 CFU/kg of the composition.
[0117] 16. The composition according to any one of embodiments 1-15, wherein the composition comprises water.
[0118] 17. The composition according to any one of embodiments 1-16, wherein the animal is bird, poultry, a human, or a non-human mammal.
[0119] 18. The composition according to any one of embodiments 1-17, wherein the animal is poultry and increases poultry health comprises at least one of: decreasing feed conversion ratio, increasing weight, increasing lean body mass, decreasing pathogen-associated lesion formation in the gastrointestinal tract, decreasing colonization of pathogens, and decreasing mortality rate.
[0120] 19. The composition according to embodiment 18, wherein increases poultry health comprises decreasing feed conversion ratio by at least 1%, at least 5%, at least 25%, or at least 50%.
[0121] 20. The composition according to any one of embodiments 17-19, wherein increases poultry health comprises increasing poultry weight by at least 1%, at least 5%, at least 25%, or at least 50%.
[0122] 21. The composition according to any one of embodiments 17-20, wherein increases poultry health comprises decreasing pathogen-associated lesion formation in the gastrointestinal tract by at least 1%, at least 5%, at least 25%, or at least 50%.
[0123] 22. The composition according to any one of embodiments 17-21, wherein increases poultry health comprises decreasing mortality rate by at least 1%, at least 5%, at least 25%, or at least 50%.
[0124] 23. The composition according to any one of embodiments 18-22, wherein the pathogen comprises at least one of Salmonella, Clostridium, Campylobacter, Staphylococcus, Streptococcus, and E. coli bacterium.
[0125] 24. The composition according to any one of embodiments 18-23, wherein the pathogen comprises at least one of Salmonella typhimurium, Salmonella infantis, Salmonella Hadar, Salmonella enteritidis, Salmonella Newport, Salmonella Kentucky, Clostridium perfringens, Staphylococcus aureus, Streptoccus uberis, Streptococcus suis, Escherichia coli, Campylobacter jejuni, and Fusobacterium necrophorum.
[0126] 25. The composition according to any one of embodiments 17-24, wherein administered comprises in ovo administration.
[0127] 26. The composition according to any one of embodiments 17-25, wherein administered comprises spray administration.
[0128] 27. The composition according to any one of embodiments 17-26, wherein the poultry is a chicken.
[0129] 28. The composition according to any one of embodiments 17-27, wherein the poultry is a broiler chicken.
[0130] 29. The composition according to any one of embodiments 17-27, wherein the poultry is an egg-producing chicken.
[0131] 30. The method according to any one of embodiments 1-29, wherein the animal administered the composition, further exhibits at least one improved gut characteristic, as compared to an animal not administered the composition; wherein improved gut characteristics includes:
[0132] increased cyclic dipeptides, increased short chain fatty acids, increased betaine, increased dimethylglycine, increased essential amino acids, increased nucleotides, and increased myo-inositol.
[0133] 31. The composition according to any one of embodiments 1-30, wherein the animal administered the composition exhibits a shift in the microbiome content of gastrointestinal tract.
[0134] 32. The method according to embodiment 31, wherein the shift comprises an increase in the amount of Bacteroidaceae bacteria.
[0135] 33. The composition according to any one of embodiments 1-32, wherein administered comprises administration of a vaccine.
[0136] 34. The composition according to any one of embodiments 1-33, wherein the animal is poultry and the poultry is administered a vaccine prior to the administration of the composition.
[0137] 35. The composition according to any one of embodiments 1-34, wherein the animal is poultry and the poultry is administered a vaccine concurrently with the administration.
[0138] 36. The composition according to any one of embodiments 33-35, wherein the animal is poultry and the poultry is administered a vaccine, wherein said vaccine comprises a vaccine that aids in the prevention of coccidiosis.
[0139] 37. The composition according to any one of embodiments 1-36, wherein administered comprises administration of galacto-oligosaccharides (GOS).
[0140] 38. A composition according to any one of embodiments 1-37 for use in therapy.
[0141] 39. A composition according to any one of embodiments 1-38 for use in improving animal health.
[0142] 40. A composition according to any one of embodiments 1-39 for use in reducing colonization of an animal by a pathogenic bacterium.
[0143] 41. A composition according to any one of embodiments 1-40 for use in the manufacture of a medicament for reducing colonization of an animal by a pathogenic bacterium.
[0144] 42. A method for increasing animal health, the method comprising:
[0145] administering to an animal an effective amount of a composition according to any one of embodiments 1-41.
[0146] 43. The method according to embodiments 42, wherein the animal is poultry.
[0147] 44. The method according to any one of embodiments 42-43, wherein increasing animal health includes decreasing pathogen-associated lesion formation in the gastrointestinal tract, decreasing colonization of pathogens, and decreasing mortality rate.
[0148] 45. A method of treating, ameliorating the effects of, or preventing necrotic enteritis in poultry by administering a composition according to any one of embodiments 1-29 to a poultry in need thereof.
Sequence CWU
1
1
431231DNAArtificial SequenceBased on Lactobacillus reuteri sequence
1atggacaaag aagaattaga aaaaattgta ggtaataact ttgaggaaat gagtttacaa
60aaaatgacag aaattcaagg tatgggtgaa taccaagtgg attcaacacc agcagcttct
120gcgatttcac gggcaacaat tcaagtatca cgtgcatctt ctggaaaatg tctaagttgg
180ggtagtggtg cagcatttag tgcttatttt actcataaaa gatggtgcta g
231276PRTArtificial SequenceBased on Lactobacillus reuteri sequence 2Met
Asp Lys Glu Glu Leu Glu Lys Ile Val Gly Asn Asn Phe Glu Glu1
5 10 15Met Ser Leu Gln Lys Met Thr
Glu Ile Gln Gly Met Gly Glu Tyr Gln 20 25
30Val Asp Ser Thr Pro Ala Ala Ser Ala Ile Ser Arg Ala Thr
Ile Gln 35 40 45Val Ser Arg Ala
Ser Ser Gly Lys Cys Leu Ser Trp Gly Ser Gly Ala 50 55
60Ala Phe Ser Ala Tyr Phe Thr His Lys Arg Trp Cys65
70 753186DNAArtificial SequenceBased on
Lactobacillus reuteri sequence 3atggaagaaa aagaattaga aggtgtaata
gggaattcgt ttgaaagtat gactgtagag 60gaaatgacaa aaattcaagg tatgggtgaa
tatcaagtag attcgacgcc tggatatttt 120atggaaagtg ctgccttttc agctcttaca
gccaatataa caagacatgc tatgcatcat 180cattaa
186461PRTArtificial SequenceBased on
Lactobacillus reuteri sequence 4Met Glu Glu Lys Glu Leu Glu Gly Val Ile
Gly Asn Ser Phe Glu Ser1 5 10
15Met Thr Val Glu Glu Met Thr Lys Ile Gln Gly Met Gly Glu Tyr Gln
20 25 30Val Asp Ser Thr Pro Gly
Tyr Phe Met Glu Ser Ala Ala Phe Ser Ala 35 40
45Leu Thr Ala Asn Ile Thr Arg His Ala Met His His His 50
55 605373PRTArtificial SequenceBased on
Lactobacillus reuteri sequence 5Met Val Glu Ile Ala His Phe Gly Val Glu
Ala Trp Leu Asn Lys Trp1 5 10
15Glu Lys Ser Ala Thr Tyr Asp Ile Ser Gln Ser Thr Ile Ala Ser Leu
20 25 30Ser Met His Asp Leu Leu
Asn Leu Asp Gly Asn Asn Gly Glu Glu Phe 35 40
45Tyr Glu Met Leu Asp Lys Gln Gln Met Asn Tyr Gly Trp Ile
Glu Gly 50 55 60Ser Pro Glu Phe Lys
Glu Glu Val Ala Lys Leu Tyr His His Val Asp65 70
75 80Pro Glu Asn Ile Leu Gln Thr Asn Gly Ala
Thr Gly Ala Asn Ile Leu 85 90
95Ala Leu Tyr Ala Leu Ile Asn Pro Gly Asp His Val Ile Ala Glu Tyr
100 105 110Pro Ser Tyr Gln Gln
Leu Tyr Asp Ile Pro Lys Ser Leu Gly Ala Asp 115
120 125Val Asp Tyr Trp His Ile His Glu Glu Asp Asn Trp
Tyr Pro Arg Ile 130 135 140Asp Asp Leu
Lys Ala Met Val Lys Pro Asn Thr Lys Met Ile Cys Leu145
150 155 160Asn Asn Ala Asn Asn Pro Thr
Gly Thr Val Leu Asp Lys Glu Phe Leu 165
170 175Glu Gln Val Val Glu Ile Ala Lys Ser Val Asp Ala
Tyr Val Leu Val 180 185 190Asp
Glu Val Tyr Leu Pro Leu Asp His Pro Glu Lys Phe Ala Gln Ile 195
200 205Ile Asp Leu Tyr Asp Lys Gly Ile Ser
Thr Asn Ser Leu Ser Lys Thr 210 215
220Tyr Ser Val Pro Gly Val Arg Ile Gly Trp Thr Ala Thr Asn Ala Glu225
230 235 240Val Ala Asp Ile
Phe Arg Lys Phe Arg Asp Tyr Thr Met Ile Cys Gly 245
250 255Gly Val Phe Asn Asp Gln Leu Ala Thr Tyr
Val Leu Arg His Arg Asp 260 265
270Gln Val Leu Ala Arg Asn Arg Lys Leu Val Leu Gly Asn Leu Ala Ile
275 280 285Tyr Lys Asp Trp Ile Asp His
Glu Asp Arg Ala Ser Val Ile Met Pro 290 295
300Gln Ala Val Ser Thr Ser Phe Pro Lys Leu Asp Val Pro Val Asp
Ile305 310 315 320His Thr
Phe Cys Glu Asn Leu Leu His Asp Glu Gly Val Leu Leu Val
325 330 335Pro Gly Asp Ala Phe Asp Thr
Pro Gly His Val Arg Leu Gly Tyr Cys 340 345
350Ala Pro Glu Ala Thr Leu Lys Glu Gly Leu Lys Arg Leu Ser
Lys Tyr 355 360 365Met His Gln Tyr
Asp 3706178PRTArtificial SequenceBased on Lactobacillus reuteri
sequence 6Met Ile Leu Thr Thr Phe Ile Ile Leu Ile Leu Met Gly Cys Phe
Ile1 5 10 15Asn Gly His
Arg Arg Gly Leu Leu Thr Met Thr Leu Met Leu Gly Thr 20
25 30Tyr Ile Val Ala Trp Ile Val Ala Arg Gln
Gly Ala Gln Leu Ile Gly 35 40
45Gly Trp Leu Lys Ser Leu Leu Pro Ser Ile Gly Thr Pro Ala Thr Phe 50
55 60Ser Glu Ser Leu Leu Ala Asn Val Asn
Ser Asn Leu Phe Phe Tyr Asn65 70 75
80Gly Ile Ala Phe Met Ile Ile Phe Thr Ile Val Ser Ile Leu
Cys His 85 90 95Trp Gly
Ile Arg Gln Leu Asn Trp Ile Lys Arg Ile Pro Val Val Gly 100
105 110Thr Val Asp Lys Ile Ala Gly Gly Leu
Ile Ser Phe Leu Ile Gly Tyr 115 120
125Leu Ile Ile Tyr Val Val Leu Leu Ile Met Gln Leu Phe Pro Ala Gly
130 135 140Trp Trp Gln Met Gln Ile Ala
Asn Ser Glu Leu Ala Arg Phe Met Ile145 150
155 160Asn Gln Thr Pro Gly Ile Ala His Leu Val Ile Asp
Thr Leu Val Gln 165 170
175Gly Gly7332PRTArtificial SequenceBased on Lactobacillus reuteri
sequence 7Met Asn Glu Tyr Asn Ala Glu Met Ala Lys Leu Asn Gln Gly Ala
Asn1 5 10 15Ala Pro Val
Ile Thr Thr Asn Ser Val Asn Gln Ala Leu Ser Leu Lys 20
25 30Pro Glu Asn Asn Ala Thr Val Asp Ile Glu
Ala Leu Asn Pro Arg Ile 35 40
45Thr Phe Lys Arg Val Glu Glu Gly Thr Lys Tyr Ala Gly Tyr Gln Ile 50
55 60Phe Asp Lys Asn Asn Ala Tyr Val Asn
Asn Ile Asp Gly Glu Phe Leu65 70 75
80Arg Val Thr Tyr Thr Asn Leu Lys Asn Ser Thr Tyr Lys Gly
Ser Lys 85 90 95Ile Ser
Lys Ile Val Val Thr Tyr Ser Asp Ser Thr Pro Thr Gly Asn 100
105 110Arg Ile Thr Gln Ser Gly Leu Asn Ala
Val Thr Glu Gly Ala Asn Asp 115 120
125Asn Phe Leu Val Val Phe Glu Asp Pro Val Arg Gly Asp Met His Ser
130 135 140Thr Thr Val Thr Ala Thr Tyr
Gln Tyr Tyr Asp Ala Asn Gly Asn Leu145 150
155 160Ile Asp Phe Ser Gly Thr Asn Asn Ala Trp Leu Ser
Val Gly Ser Leu 165 170
175Asn Phe Asp Gln Gly Asn Asp Tyr Gln Gly Gly Lys Asn Glu Gly Asn
180 185 190Pro Thr Ser Gly Ile Ser
Glu Gly Val Lys Leu Ile Ser Gly Ala Gln 195 200
205Ile Lys Gln Leu Ala Gly Ser Ser Ile Ser Val His Asp Asp
Gly Trp 210 215 220Ala Tyr Ala Gly Phe
Asn Asn Tyr Ser Gly Thr Gly Met Asn Asn Gly225 230
235 240Ile Asn Thr Asp Asn Gly Gly Ser Gly Trp
Asp Met Asp Gly Ser Pro 245 250
255Asn Ala Tyr Tyr Gly Ala Ile Val Phe Gln Leu Thr Gly Ser Ser Val
260 265 270Ser Leu Arg Gln Gly
Leu Val Ser Trp Gly Gly Ala Asp Ile Ala Ser 275
280 285Gln Tyr Asn Asn Gln Phe Leu Asn Asn Ala Trp Phe
Thr Ala Gly Thr 290 295 300Thr Leu Pro
Glu Thr Gln Ile Lys Gln Pro Ile Arg Lys Thr Ser Glu305
310 315 320Thr His Tyr His Tyr Asn Pro
Ser Val Ile Arg Leu 325
33082059PRTArtificial SequenceBased on Lactobacillus reuteri sequence
8Met Ala Gln Lys Leu Met Ser Ala Asn Ser Thr Asp Lys Asn Phe Lys1
5 10 15Met Tyr Lys Ser Lys Lys
Ser Trp Val Phe Ala Tyr Ser Thr Thr Leu 20 25
30Ala Leu Ala Ala Val Ala Gly Ile Thr Leu Ser Thr Thr
Asn Val His 35 40 45Ala Asp Thr
Thr Asn Gly Gly Asp Asn Gln Val Asn Ala Thr Ala Val 50
55 60Thr Gln Asn Thr Thr Ser Asn Thr Val Asp Gln Ile
Ala Ala Asn Thr65 70 75
80Ala Gln Thr Asp Asn Thr Ser Thr Ser Ile Asn Ile Arg Ser Leu Met
85 90 95Asp Asp Leu Ala Ser Gly
Asp Asp Thr Ser Ser Ser Gln Asn Gly Gln 100
105 110Glu Gln Ser Gln Asn Tyr Ala Ser Ser Asn Gln Asn
Ser Gln Thr Gln 115 120 125Gln Glu
Asn Gly Thr Thr Gly Gln Ser Thr Ala Ser Gln Asn Gly Thr 130
135 140Thr Ser Asp Gln Thr Asn Ser Asp Gln Ser Asp
Lys Asn Tyr Tyr Val145 150 155
160Ile Ser Thr Arg Asp Leu Asp Lys Asn Gly Asn Val Asn Tyr Leu Thr
165 170 175Gln Lys Asn Tyr
Thr Ser Ile Lys Gly Gln Glu Val Ala Asp Gly Thr 180
185 190Val Val Thr Trp Pro Leu Ser Val Ser Ala Leu
Pro Ala Asn Arg Ala 195 200 205Gln
Asp Leu Lys Ser His Val Ile Ser Glu Thr Leu Asp Pro His Leu 210
215 220Glu Tyr Leu His Tyr Arg Ala Tyr Leu Thr
Asn Thr Asp Gly Thr Val225 230 235
240Thr Asp Val Thr Asn His Val Asn Leu Asn Arg Ser Gly Gln Thr
Leu 245 250 255Ile Phe Thr
Asp Asp Asn Tyr Leu Leu Ser Ile Tyr Asn Asn Asn Arg 260
265 270Tyr Arg Val Gln Asn Leu Pro Val Ile Lys
Leu Val Thr Lys Ala Asn 275 280
285Gly Asn Gly Tyr Ile Ile Pro Asn Ala Phe Lys Ser Ser Tyr Val Phe 290
295 300Asn Asp Gly Ser His Asp Val Ser
Phe Thr Thr Thr Ser Asn Asn Val305 310
315 320Gln Ile Lys Thr Phe Asn Pro Gly Asn Ser Lys Asp
Val Glu Ile Gly 325 330
335Gly Asn Val Gln Gly Asp Pro Ser Gly Thr Ile Asn Gly Gln Val Val
340 345 350Ala Asp Gly Ser Val Val
Thr Trp Pro Met Ser Val Gly Asp Leu Pro 355 360
365Ala Asn Arg Ala Gln Asp Val Leu Ser His Ile Glu Thr Asp
Thr Leu 370 375 380Tyr Asn Gly Leu Asn
Tyr Glu Gly Tyr His Ala Tyr Leu Pro Gln Ala385 390
395 400Asp Gly Ser Phe Gln Asp Val Ser Ser His
Ile Asn Val Gln Gln Asn 405 410
415Gly Gln Asp Leu Thr Phe Ile Ala Asp Asp Tyr Leu Ile Gly Leu Tyr
420 425 430Asn Gln Asp Lys Ser
Thr Ala Phe Lys Met Pro Ile Ile Asp Leu Ile 435
440 445Thr Ser Val His Gly Thr Ser Ile Ile Ala Pro Asn
Lys Phe Asn Ser 450 455 460Gln Leu Ala
Phe Lys Asp Gly Asn Gly Gln Thr Val Ile Asn Asn Thr465
470 475 480Ser Asn Gln Val Gln Ile Ser
Thr Tyr His Pro Thr Asn Thr Lys Asp 485
490 495Val Glu Leu Gly Gly Asn Val Gln Gly Asp Thr Pro
Asn Ser Ile Asn 500 505 510Asp
Lys Val Val Ala Asn Gly Ala Ile Val Thr Trp Pro Met Ala Ser 515
520 525Ser Glu Leu Pro Ala Asn Arg Val Gln
Asp Leu Gln Ser Arg Val Ile 530 535
540Ser Glu Thr Leu Asp Ser His Leu Gln Tyr Gln Gly Tyr Lys Ala Trp545
550 555 560Leu Gln Asn Ala
Asp Gly Lys Tyr Thr Asp Val Thr Ser His Val Lys 565
570 575Leu Thr Gln Asp Gly Gln Asn Leu Thr Phe
Ala Asp Asp Glu Tyr Leu 580 585
590Leu Asn Leu Tyr Asn Ser Asn Lys Gly Thr Ala Tyr Lys Leu Pro Ile
595 600 605Ile Asp Leu Val Thr Lys Val
Asn Gly Ala Gly Ile Thr Ala Pro Asn 610 615
620Ser Tyr Thr Thr Lys Tyr Val Tyr Ser Asp Gly Asp Gly Asn Thr
Thr625 630 635 640Ile Asn
Val Thr Ser Asn Thr Val Lys Ile Ser Thr Phe Asn Pro Thr
645 650 655Thr Asn Lys Asp Val Glu Leu
Gly Asp Asn Ile His Gly Asp Thr Glu 660 665
670Ser Ser Ile Ala Gly Lys Leu Val Ser Glu Gly Thr Ile Val
Thr Trp 675 680 685Pro Leu Ser Thr
Ser Asp Leu Pro Ala Asn Arg Ala Gln Asp Val Val 690
695 700Ser His Thr Ala Val Asp Ala Leu Glu Pro Thr Leu
Gln Tyr Ile Ser705 710 715
720Tyr Thr Ala Trp Leu Pro Asp Ser Asn Gly Gln Leu Gln Asp Val Thr
725 730 735Ser His Val Lys Met
Thr Arg Asp Gly Gln Lys Leu Thr Phe Thr Asp 740
745 750Asp Asp Tyr Leu Ile Gly Leu Tyr Asn Gln Asn Lys
Asp Ile Ala Leu 755 760 765Lys Met
Pro Ile Ile Asp Leu Val Thr Lys Ala Thr Gly Asn Thr Lys 770
775 780Leu Leu Pro Asn Ser Phe Asp Ser Gln Phe Val
Tyr Asn Asp Val Asp785 790 795
800Gly Asn Thr Ile Ile Asn Val Ser Ser Asn Lys Pro Thr Val Glu Thr
805 810 815Phe Asp Pro Thr
Val His Lys Asp Val Glu Leu Gly Gly Asn Asn Val 820
825 830Gln Gly Asp Thr Pro Asn Ser Ile Asp Gly Lys
Ile Val Ala Gln Gly 835 840 845Thr
Val Val Thr Trp Pro Met Ser Thr Ser Asp Leu Pro Ala Asn Arg 850
855 860Thr Gln Asp Val Val Ser His Ser Thr Ser
Glu Thr Leu Asn Gln Asn865 870 875
880Leu Gln Tyr Val Gly Tyr His Ala Tyr Met Pro Asp Ala Asn Gly
Lys 885 890 895Leu Gln Asp
Val Thr Ser His Val Gln Leu Gln Gln Asn Gly Gln Asn 900
905 910Leu Val Phe Thr Asp Asp Ser Tyr Leu Ile
Asn Leu Tyr Asn Gln Asp 915 920
925Lys Ser Ile Ala Phe Lys Met Pro Ile Ile Asp Leu Met Thr Lys Ala 930
935 940Ile Ser Asp Ser Ala Thr Ile Pro
Asn Thr Phe Glu Ser Gln Tyr Val945 950
955 960Phe Asn Asp Gly Asn Gly Asn Thr Thr Phe Lys Ser
Thr Ser Asn Thr 965 970
975Val Gln Ile Ile Thr Tyr Lys Pro Lys Thr Thr Lys Asp Val Glu Leu
980 985 990Gly Asp Asn Ile His Gly
Asp Thr Asn Ala Ser Ile Ala Gly Gln Met 995 1000
1005Ile Thr Asp Gly Thr Val Val Thr Trp Pro Met Ser
Thr Ser Asp 1010 1015 1020Leu Pro Ala
Asn Arg Thr Gln Asp Leu Gln Gln His Val Val Thr 1025
1030 1035Asp Asn Leu Asn Asp Asn Leu Ile Phe Gln Gly
Tyr Thr Ala Trp 1040 1045 1050Leu Pro
Thr Ala Asn Gly Leu Val Asp Val Thr Asn His Ile Glu 1055
1060 1065Leu Thr Arg Asp Gly Gln Asn Leu Thr Phe
Thr Asp Asp Ala Tyr 1070 1075 1080Leu
Leu Asn Leu Tyr Asn Gln Asn Lys Asp Thr Ala Tyr Lys Leu 1085
1090 1095Pro Ile Ile Asp Leu Val Thr Lys Ala
Asn Gly Asn Thr Lys Leu 1100 1105
1110Ile Pro Asn Asn Phe Asp Ser Met Phe Val Tyr Asn Asp Gly Asp
1115 1120 1125Gln Gln Thr Thr Val Asn
Val Thr Ser Asn Thr Val Asn Ile Ser 1130 1135
1140Thr Tyr Asp Pro Thr Ala Thr Lys Asp Val Glu Leu Gly Asp
Asp 1145 1150 1155Ile Glu Gly Asp Thr
Ala Asp Thr Ile Asn Asn Leu Met Val Gln 1160 1165
1170Ile Gly Thr Lys Met Thr Tyr Pro Leu Thr Val Ser Asp
Leu Pro 1175 1180 1185Ala Asn Arg Ala
Asp Glu Ile Thr Ala His Gln Ser Val Asp Thr 1190
1195 1200Leu Ser Asp Tyr Leu Glu Tyr Gln Gly Tyr Lys
Ala Tyr Leu Pro 1205 1210 1215Asp Ala
Asp Gly Lys Leu Gln Asp Ile Thr Glu His Val Asn Leu 1220
1225 1230Lys Arg Glu Gly Gln Lys Leu Ser Phe Asn
Asp Asp Asp Tyr Leu 1235 1240 1245Ile
Asn Leu Tyr Asn Asn Ser Lys Ala Thr Lys Gln Ala Leu Pro 1250
1255 1260Val Ile Asp Leu Val Ala Lys Val Thr
Gly Ser Asn Asp Gly Lys 1265 1270
1275Lys Val His Ile Ile Pro Asn His Phe Asp Ser Thr Ile Thr Thr
1280 1285 1290Lys Asp Gly Lys Ile Asn
Thr Thr Ser Asn Thr Val Val Ile Asn 1295 1300
1305Ser Asn Asp Pro Glu Ala Val Lys Asp Val Glu Leu Gly Asp
Asn 1310 1315 1320Val Val Gly Asp Thr
Pro Asn Ser Val Thr Gly Thr Thr Val Ala 1325 1330
1335Asp Gly Thr Ile Val Thr Trp Pro Met Ser Val Gly Ser
Leu Gly 1340 1345 1350Ala Asn Arg Ala
Gln Asn Val Ile Lys His Thr Glu Thr Glu Asn 1355
1360 1365Leu Asp Ser Gly Leu Thr Tyr Leu Ser Phe Lys
Ala Tyr Leu Pro 1370 1375 1380Asp Ala
Asp Gly Lys Met Gln Asp Ile Thr Glu His Ile Asn Ile 1385
1390 1395Gln Gln Asp Gly Gln Lys Leu Val Phe Thr
Asp Asp Asp Tyr Leu 1400 1405 1410Ile
Ser Leu Tyr Asn Lys Asp Lys Ser Gln Arg Phe Ala Leu Pro 1415
1420 1425Val Ile Asp Leu Val Thr Arg Val Asn
Gly Asp Asn Lys Ile Ile 1430 1435
1440Pro Asn Thr Phe Val Ser Gln Phe Thr Phe Asn Asp Gly Lys Gly
1445 1450 1455Asn Thr Ile Thr Ser Val
Thr Ser Asn Gln Val Asn Val Ser Thr 1460 1465
1470Phe Lys Ser Asn Pro Glu Lys His Val Thr Leu Gly Thr Asp
Ile 1475 1480 1485Glu Gly Asp Asp Ala
Glu Asn Ala Asp Gly Thr Val Val Ala Gln 1490 1495
1500Gly Ser Glu Val Thr Trp Pro Leu Ser Asp Lys Ser Pro
Leu Pro 1505 1510 1515Ala Asn Arg Ser
Gln Asp Val Lys Ser His Thr Leu Val Asp Lys 1520
1525 1530Leu Asp Asp Asn Leu Gln Tyr Asn Ser Tyr Lys
Ala Tyr Leu Lys 1535 1540 1545Gly Thr
Asp Gly Lys Leu Gln Asp Val Thr Asp His Ile Lys Leu 1550
1555 1560Thr Arg Asp Gly Gln Asn Leu Thr Phe Ile
Asp Asp Asp Tyr Leu 1565 1570 1575Leu
Asp Leu Tyr Asn Lys Asp Lys Ser Thr Ala Phe Asn Leu Pro 1580
1585 1590Ile Ile Asp Leu Val Thr Thr Val Val
Gly Asn Asp Lys Leu Ile 1595 1600
1605Pro Asn Lys Phe Asp Ser Asn Phe Val Phe Ser Asp Gly Asn Lys
1610 1615 1620Asp Thr Ser Met Lys Thr
Thr Ser Asn Glu Val Ser Ile Ser Thr 1625 1630
1635Tyr Thr Pro Val Thr Asn Lys Asp Ala Glu Leu Gly Asp Asn
Val 1640 1645 1650Val Gly Asp Thr Ser
Asp Ser Ile Ala Asn Glu Thr Val Pro Asp 1655 1660
1665Gly Thr Ile Val Thr Trp Pro Leu Ser Val Ser Ser Leu
Pro Ala 1670 1675 1680Asn Arg Ser Gln
Asp Val Phe Lys His Val Ile Glu Asp Ile Leu 1685
1690 1695Asp Gly Asn Leu Thr Tyr Asn Ser Phe Lys Ala
Tyr Leu Lys Asp 1700 1705 1710Ala Ala
Gly Asn Leu Gln Glu Val Thr Asp His Val Lys Leu Ala 1715
1720 1725Gln Glu Gly Gln His Leu Thr Phe Thr Asp
Asp Asp Tyr Leu Ile 1730 1735 1740Asn
Leu Tyr Asn Ser Ser Lys Asn Lys Glu Gln Ser Leu Pro Ile 1745
1750 1755Ile Asp Leu Val Thr Thr Val His Gly
Asp Ser Lys Leu Ile Pro 1760 1765
1770Asn Glu Phe Asp Asn Val Phe Val Phe Lys Asp Gly Lys Gly Gln
1775 1780 1785Thr Thr Val Lys Thr Thr
Ser Asn Lys Val Thr Ile Lys Thr Ala 1790 1795
1800Ser Leu Pro Thr Pro Thr Lys Glu Glu Thr Asp Asp Gln Gly
Asn 1805 1810 1815Asn Ile Asn Gly Asn
Glu Val Lys Ala Gly Glu His Val Asn Tyr 1820 1825
1830Thr Leu Asn Trp Asp Leu Ser Asn Asp Lys Asp Val Lys
Ala Thr 1835 1840 1845Pro Glu Met Ile
Lys Lys Gly Phe Phe Phe Ile Asp Pro Ile Asp 1850
1855 1860Ser Arg Ala Leu Ser Val Asp Asp Leu Ser Lys
Ala Lys Val Val 1865 1870 1875Asp Gln
Asn Gly Asn Lys Val Asp Gly Ile Ser Phe His Leu Tyr 1880
1885 1890Asn Ser Leu Ser Glu Val Pro Glu Phe Ile
Gln Glu Gln Val Lys 1895 1900 1905Ala
Asn Asn Leu Gln Asp Lys Ile Thr Gly Pro Phe Val Val Ala 1910
1915 1920Gln Ala Asp Asp Leu Gln Ala Phe Phe
Asp Lys Tyr Val Lys Thr 1925 1930
1935Gly Ala Lys Leu Lys Val Thr Ile Pro Thr Ile Val Lys Ser Gly
1940 1945 1950Phe Thr Gly Glu Phe Ser
Asn Thr Ala Tyr Gln Phe Gly Phe Gly 1955 1960
1965Lys Ala Thr Pro Thr Asn Thr Val Thr Asn Tyr Val Lys Pro
Met 1970 1975 1980His Lys Pro Ala Ser
Pro Glu Thr Pro Ala Ala Ile Ala Pro Gln 1985 1990
1995Val Ile Ser Ala Thr Ala Gln Pro Met Thr Ser Asp Ala
Pro Val 2000 2005 2010Thr Pro Ser Glu
Lys Thr Ala Lys Leu Pro Gln Thr Gly Asn Ala 2015
2020 2025Asp Glu Gly Ala Leu Leu Gly Leu Ala Ala Val
Ser Leu Val Gly 2030 2035 2040Ser Leu
Gly Leu Ala Ala Leu Gly Leu Lys Gln Asn Arg Asn Asp 2045
2050 2055Asp9300DNAArtificial SequenceBased on
Lactobacillus reuteri sequence 9ttaaagtatt aaaatagatg taaaatttat
ttttttcaaa agaaatttta attgtacact 60gttggtattg aacggggtta aacaaaggta
aattagcatt tctgcggatt aagataaata 120gaaaaatgtt aaagaacacc ttaaaaagat
taatttttta taattggacc gtatcaattt 180gtaaaaaggt tgactttttg aaaaaaaagt
ttatcattaa cattgtaaat ttaatgattt 240acgttatgtt gttatagagc acaggacgta
ttgatttata tagaaggagt gtttattaga 30010300DNAArtificial SequenceBased
on Lactobacillus reuteri sequence 10atgaatggac agatgtttta atcgctagaa
tagaaggaaa gaaagtcgca acaaatacgg 60tttctagtac gtggcaggaa cgactaggta
agcagattga cgaattaata gaaaaacatt 120agtcaaatac atttacaaat gaacagatag
ttgatattat atttaagaat tcttcttcag 180agcctaagat taaagctttc aattggcgaa
aagaagttgt acaatatgta taaaggtatg 240tcagtcaccg aatcagatga tctggcatta
tacttgtaaa ttatcaggag gttttcatta 30011300DNAArtificial SequenceBased
on Lactobacillus reuteri sequence 11atctcacgtg cgatccatta cactaagggc
gcgtcaacaa atattatact atcttaaata 60agaatgaatt gcaagcatta tttgaaaatt
ttaattaaaa taacgcttac atcagaaaaa 120tgttgtgatt gaatagacaa tttttttgaa
gatggtatca taagtatcgt aggagttgta 180ttattgctta gaccttacca ctgcgtcact
tacaatggtt gagagttgcg atgctgatgt 240aatgtgataa actaagcaag tacactaatt
atgttttttc ctaaaggagg aatttgcagt 30012300DNAArtificial SequenceBased
on Lactobacillus reuteri sequence 12ttgtttaaga tatctttcaa agctgcggaa
tttttcccag cttttttagt tagttttgtt 60ttcataagct ataattttaa ccgattccaa
atttctttta aaagtttttt tgatctagac 120cattaattga taaacgctta ccaaagacta
atcaacaagc catttagcgg tagtggtcca 180ttttaacttt ctaagacatc ttctcagaaa
acgtttcctt tgatagtgca gattgtgctt 240taagagtata taattgtcac ggtataagaa
ttttctgaaa tttcagaagg agtgaacatt 30013449DNAArtificial SequenceBased
on Lactobacillus reuteri sequence 13ctcctctatt attattcctg atcaatttta
aattaatctc cctagatagg tatattttag 60cacaggtcac caacgttcca aagtttaatc
tatgtttaaa ctttaatttt caaaaaaatg 120ctatactatg ttcacgatac tttaaggaaa
ggtgattaca atagtgagtc tcttaattgc 180tattcttatc tgctggttgc tatggaagat
tgggggttta acggttaagt tcattggtct 240aatccttctt attctattaa tcgggacatt
aattcatgtt ttactttggc cagcgatcct 300tttagcagtt attatcttag gagcaggttt
attcactaac taatttatct ataaaatctt 360atagtaattt ttctgcggaa tgttataatc
attactgtga gagaaatctc aaataatgta 420tacataagat gaaagggaga ctgtttatt
44914250DNAArtificial SequenceBased on
Lactobacillus reuteri sequence 14acaaatacgg tttctagtac gtggcaggaa
cgactaggta agcagattga cgaattaata 60gaaaaacatt agtcaaatac atttacaaat
gaacagatag ttgatattat atttaagaat 120tcttcttcag agcctaagat taaagctttc
aattggcgaa aagaagttgt acaatatgta 180taaaggtatg tcagtcaccg aatcagatga
tctggcatta tacttgtaaa ttatcaggag 240gttttcatta
250153017PRTArtificial SequenceBased on
Lactobacillus reuteri sequence 15Met Val Ser Lys Asn Asn His Gln Phe Tyr
Gln Gln Lys His Ala Glu1 5 10
15Arg Lys Gln Arg Trp Gly Ile Arg Lys Leu Ser Val Gly Val Ala Ser
20 25 30Val Leu Leu Gly Thr Thr
Phe Met Leu Tyr Gly Asn His Ala Val Leu 35 40
45Ala Asp Thr Val Thr Ser Pro Ser Asp Asp Val Thr Arg Ser
Thr Thr 50 55 60Thr Gln Gly Gly Asn
Lys Asp Lys Val Thr Glu Gly Thr Thr Glu Gly65 70
75 80Thr Thr Ser Thr Pro Gln Thr Ser Gly Asp
Ser Thr Asp Lys Gln Ala 85 90
95Asn Gly Gln Asn Val Asn Gln Gln Val Pro Thr Thr Asp Thr Glu Glu
100 105 110Ala Thr Asn His Gln
Asp Thr Pro Gln Gly Gln Asp Thr Thr Gln Asn 115
120 125Thr Thr Asn Val Asp Lys Lys Asp Thr Glu Val Thr
Pro Ala Asn Asp 130 135 140Ala Thr Thr
Pro Thr Thr Gln Lys Ile Thr Ala Lys Phe Thr Thr Ala145
150 155 160Lys Phe Thr Thr Ala Lys Phe
Thr Ala Ala Lys Phe Lys Val Leu Ala 165
170 175Ala Arg Pro Val Met Lys Val Ala Gly Thr Ala Ser
Leu Pro Ile Ser 180 185 190Asn
Gln Asp Ile Lys Leu Asp Ser Gln Pro Met Leu Thr Glu Ile Ile 195
200 205Asn Lys Pro Thr Asp Asn Trp Val Tyr
Asn Asn Leu Lys Trp Tyr Gln 210 215
220Asp Thr Ser Thr Glu Lys Ile Lys Glu Ile Leu Gln Asn His Thr Ala225
230 235 240Asn Asp Glu Ser
Gly Arg Tyr Tyr Phe Ala Gly Val Ala Asn Tyr Asn 245
250 255Glu His Tyr His Ala Ile Tyr Leu Leu Ala
Arg Ser Asn Asn Leu Asn 260 265
270Asp Asn Ser Leu Tyr Val Thr Ile Leu His Thr Gly Leu Gly Lys Asn
275 280 285Ile Gln Glu Ala Val Val Ala
Pro Gly Glu Ser Lys Lys Val Glu Tyr 290 295
300Ser Gly Thr Thr His Thr Pro Ile Phe Thr Asn Tyr Asp Gly Thr
Ser305 310 315 320Ala Ser
Ile Asp Leu Asp Gly Ile Glu Lys Gly Asp Asn Ile Tyr Gly
325 330 335Met Val Val Gly Phe Ala Tyr
Gly His Asn Thr Gly Ile Lys Gly Asp 340 345
350Pro Ala Ser Met Gly Asn Gly Phe Val Met Thr Pro Ile Pro
Thr Lys 355 360 365Met Thr Thr Thr
Ile His Tyr Ile Asp Gln Ala Thr Gly Asp Glu Ile 370
375 380Ala Val Pro Lys Ser Phe Glu Gly Val Ala Tyr Gln
Lys Tyr Thr Ile385 390 395
400Thr Gly Glu Ala Pro Thr Ile Asp Gly Tyr Thr Leu Lys Lys Ser Pro
405 410 415Glu Thr Thr Gly Tyr
Ile Ser Pro Tyr Lys Val Gly Glu Ser Tyr Asp 420
425 430Phe Arg Leu Asp Lys His Val Val Ile Lys Gln Thr
Val Ile Asp Ala 435 440 445Gln Gly
Leu Val Arg Val Thr Ala Tyr Tyr Asp Gly Glu Val Leu Asn 450
455 460Asn Thr Thr Arg Tyr Leu Gly Asn Lys Leu Asn
Val Asn Asp Arg Met465 470 475
480Ser Phe Ile Ser His Gly Lys Trp Tyr Thr Tyr Ile Asn Gln Ile Thr
485 490 495Ser Thr Asn Asp
Gly Ile Val Tyr Tyr Tyr Ala Lys Asp Gly Ser Glu 500
505 510Asp Lys Ser Glu Val Arg Val His Tyr Ile Asp
Val Thr Gly Ser Lys 515 520 525Asn
Ser Ile Phe Val Pro Gly Asp Gly Glu Glu Val Ala Thr Asp Lys 530
535 540Ile Ser Gly Lys Leu Gly Glu Asn Tyr Asn
Tyr Asp Val Asn Leu Pro545 550 555
560Thr Asp Tyr Asn Leu Ala Thr Asn Gln Ala Asn Thr Val Asn Gly
Thr 565 570 575Tyr Thr Ile
Asp His His Asp Glu Tyr Val Tyr Val Val Lys Lys Thr 580
585 590Ser Ala Glu Leu Asp Pro Thr Val Pro Ala
Lys Thr Lys Val Asp Asn 595 600
605Pro Thr Ser Leu Thr Ala Asp Glu Lys Lys Thr Ile Glu Asp Lys Ile 610
615 620Val Glu Ala Asn Lys Asp Lys Phe
Pro Glu Gly Thr Gly Val Thr Val625 630
635 640Ala Asn Asp Gly Lys Ala Thr Ile Thr Tyr Pro Asp
Lys Ser Val Asp 645 650
655Thr Ile Glu Gly Asn Gln Leu Val Glu Glu Lys Thr Ser Ala Glu Lys
660 665 670Leu Asp Pro Thr Val Pro
Ala Lys Thr Lys Val Asp Asn Pro Thr Ser 675 680
685Leu Thr Ala Asp Glu Lys Lys Thr Ile Glu Asp Lys Ile Val
Glu Ala 690 695 700Asn Lys Asp Lys Phe
Pro Glu Gly Thr Gly Val Thr Val Ala Asn Asp705 710
715 720Gly Lys Ala Thr Ile Thr Tyr Pro Asp Lys
Ser Val Asp Thr Ile Glu 725 730
735Gly Asn Gln Leu Val Glu Glu Lys Thr Ser Ala Glu Lys Leu Asp Pro
740 745 750Thr Val Pro Ala Lys
Thr Lys Val Asp Asn Pro Thr Ser Leu Thr Ala 755
760 765Asp Glu Lys Lys Thr Ile Glu Asp Lys Ile Val Glu
Ala Asn Lys Asp 770 775 780Lys Phe Pro
Glu Gly Thr Gly Val Thr Val Ala Asn Asp Gly Lys Ala785
790 795 800Thr Ile Thr Tyr Pro Asp Lys
Ser Val Asp Thr Ile Glu Gly Asn Gln 805
810 815Leu Val Glu Glu Lys Thr Ser Ala Glu Lys Leu Asp
Pro Thr Val Pro 820 825 830Ala
Lys Thr Lys Val Asp Asn Pro Thr Ser Leu Thr Ala Asp Glu Lys 835
840 845Lys Thr Ile Glu Asp Lys Ile Val Glu
Ala Asn Lys Asp Lys Phe Pro 850 855
860Glu Gly Thr Gly Val Thr Val Ala Asn Asp Gly Lys Ala Thr Ile Thr865
870 875 880Tyr Pro Asp Lys
Ser Val Asp Thr Ile Glu Gly Asn Gln Leu Val Glu 885
890 895Glu Lys Thr Ser Ala Glu Lys Leu Asp Pro
Thr Val Pro Ala Lys Thr 900 905
910Lys Val Asp Asn Pro Thr Ser Leu Thr Ala Asp Glu Lys Lys Thr Ile
915 920 925Glu Asp Lys Ile Val Glu Ala
Asn Lys Asp Lys Phe Pro Glu Gly Thr 930 935
940Gly Val Thr Val Ala Asn Asp Gly Lys Ala Thr Ile Thr Tyr Pro
Asp945 950 955 960Lys Ser
Val Asp Thr Ile Glu Gly Asn Gln Leu Val Glu Glu Lys Thr
965 970 975Ser Ala Glu Lys Leu Asp Pro
Thr Val Pro Ala Lys Thr Lys Val Asp 980 985
990Asn Pro Thr Ser Leu Thr Ala Asp Glu Lys Lys Thr Ile Glu
Asp Lys 995 1000 1005Ile Val Glu
Ala Asn Lys Asp Lys Phe Pro Glu Gly Thr Gly Val 1010
1015 1020Thr Val Ala Asn Asp Gly Lys Ala Thr Ile Thr
Tyr Pro Asp Lys 1025 1030 1035Ser Val
Asp Thr Ile Glu Gly Asn Gln Leu Val Glu Glu Lys Thr 1040
1045 1050Ser Ala Glu Lys Leu Asp Pro Thr Val Pro
Ala Lys Thr Lys Val 1055 1060 1065Asp
Asn Pro Thr Ser Leu Thr Ala Asp Glu Lys Lys Thr Ile Glu 1070
1075 1080Asp Lys Ile Val Glu Ala Asn Lys Asp
Lys Phe Pro Glu Gly Thr 1085 1090
1095Gly Val Thr Val Ala Asn Asp Gly Lys Ala Thr Ile Thr Tyr Pro
1100 1105 1110Asp Lys Ser Val Asp Thr
Ile Glu Gly Asn Gln Leu Val Glu Glu 1115 1120
1125Lys Thr Ser Ala Glu Lys Leu Asp Pro Thr Val Pro Ala Lys
Thr 1130 1135 1140Lys Val Asp Asn Pro
Thr Ser Leu Thr Ala Asp Glu Lys Lys Thr 1145 1150
1155Ile Glu Asp Lys Ile Val Glu Ala Asn Lys Asp Lys Phe
Pro Glu 1160 1165 1170Gly Thr Gly Val
Thr Val Ala Asn Asp Gly Lys Ala Thr Ile Thr 1175
1180 1185Tyr Pro Asp Lys Ser Val Asp Thr Ile Glu Gly
Asn Gln Leu Val 1190 1195 1200Glu Glu
Lys Thr Ser Ala Glu Lys Leu Asp Pro Thr Val Pro Ala 1205
1210 1215Lys Thr Lys Val Asp Asn Pro Thr Ser Leu
Thr Ala Asp Glu Lys 1220 1225 1230Lys
Thr Ile Glu Asp Lys Ile Val Glu Ala Asn Lys Asp Lys Phe 1235
1240 1245Pro Glu Gly Thr Gly Val Thr Val Ala
Asn Asp Gly Lys Ala Thr 1250 1255
1260Ile Thr Tyr Pro Asp Lys Ser Val Asp Thr Ile Glu Gly Asn Gln
1265 1270 1275Leu Val Glu Glu Lys Thr
Ser Ala Glu Lys Leu Asp Pro Thr Val 1280 1285
1290Pro Ala Lys Thr Lys Val Asp Asn Pro Thr Ser Leu Thr Ala
Asp 1295 1300 1305Glu Lys Lys Thr Ile
Glu Asp Lys Ile Val Glu Ala Asn Lys Asp 1310 1315
1320Lys Phe Pro Glu Gly Thr Gly Val Thr Val Ala Asn Asp
Gly Lys 1325 1330 1335Ala Thr Ile Thr
Tyr Pro Asp Lys Ser Val Asp Thr Ile Glu Gly 1340
1345 1350Asn Gln Leu Val Glu Glu Lys Thr Ser Ala Glu
Lys Leu Asp Pro 1355 1360 1365Thr Val
Pro Ala Lys Thr Lys Val Asp Asn Pro Thr Ser Leu Thr 1370
1375 1380Ala Asp Glu Lys Lys Thr Ile Glu Asp Lys
Ile Val Glu Ala Asn 1385 1390 1395Lys
Asp Lys Phe Pro Glu Gly Thr Gly Val Thr Val Ala Asn Asp 1400
1405 1410Gly Lys Ala Thr Ile Thr Tyr Pro Asp
Lys Ser Val Asp Thr Ile 1415 1420
1425Glu Gly Asn Gln Leu Val Glu Glu Lys Thr Ser Ala Glu Lys Leu
1430 1435 1440Asp Pro Thr Val Pro Ala
Lys Thr Lys Val Asp Asn Pro Thr Ser 1445 1450
1455Leu Thr Ala Asp Glu Lys Lys Thr Ile Glu Asp Lys Ile Val
Glu 1460 1465 1470Ala Asn Lys Asp Lys
Phe Pro Glu Gly Thr Gly Val Thr Val Ala 1475 1480
1485Asn Asp Gly Lys Ala Thr Ile Thr Tyr Pro Asp Lys Ser
Val Asp 1490 1495 1500Thr Ile Glu Gly
Asn Gln Leu Val Glu Glu Lys Thr Ser Ala Glu 1505
1510 1515Lys Leu Asp Pro Thr Val Pro Ala Lys Thr Lys
Val Asp Asn Pro 1520 1525 1530Thr Ser
Leu Thr Ala Asp Glu Lys Lys Thr Ile Glu Asp Lys Ile 1535
1540 1545Val Glu Ala Asn Lys Asp Lys Phe Pro Glu
Gly Thr Gly Val Thr 1550 1555 1560Val
Ala Asn Asp Gly Lys Ala Thr Ile Thr Tyr Pro Asp Lys Ser 1565
1570 1575Val Asp Thr Ile Glu Gly Asn Gln Leu
Val Glu Glu Lys Thr Ser 1580 1585
1590Ala Glu Lys Leu Asp Pro Thr Val Pro Ala Lys Thr Lys Val Asp
1595 1600 1605Asn Pro Thr Ser Leu Thr
Ala Asp Glu Lys Lys Thr Ile Glu Asp 1610 1615
1620Lys Ile Val Glu Ala Asn Lys Asp Lys Phe Pro Glu Gly Thr
Gly 1625 1630 1635Val Thr Val Ala Asn
Asp Gly Lys Ala Thr Ile Thr Tyr Pro Asp 1640 1645
1650Lys Ser Val Asp Thr Ile Glu Gly Asn Gln Leu Val Glu
Glu Lys 1655 1660 1665Thr Ser Ala Glu
Lys Leu Asp Pro Thr Val Pro Ala Lys Thr Lys 1670
1675 1680Val Asp Asn Pro Thr Ser Leu Thr Ala Asp Glu
Lys Lys Thr Ile 1685 1690 1695Glu Asp
Lys Ile Val Glu Ala Asn Lys Asp Lys Phe Pro Glu Gly 1700
1705 1710Thr Gly Val Thr Val Ala Asn Asp Gly Lys
Ala Thr Ile Thr Tyr 1715 1720 1725Pro
Asp Lys Ser Val Asp Thr Ile Glu Gly Asn Gln Leu Val Glu 1730
1735 1740Glu Lys Thr Ser Ala Glu Lys Leu Asp
Pro Thr Val Pro Ala Lys 1745 1750
1755Thr Lys Val Asp Asn Pro Thr Ser Leu Thr Ala Asp Glu Lys Lys
1760 1765 1770Thr Ile Glu Asp Lys Ile
Val Glu Ala Asn Lys Asp Lys Phe Pro 1775 1780
1785Glu Gly Thr Gly Val Thr Val Ala Asn Asp Gly Lys Ala Thr
Ile 1790 1795 1800Thr Tyr Pro Asp Lys
Ser Val Asp Thr Ile Glu Gly Asn Gln Leu 1805 1810
1815Val Glu Glu Lys Thr Ser Ala Glu Lys Leu Asp Pro Thr
Val Pro 1820 1825 1830Ala Lys Thr Lys
Val Asp Asn Pro Thr Ser Leu Thr Ala Asp Glu 1835
1840 1845Lys Lys Thr Ile Glu Asp Lys Ile Val Glu Ala
Asn Lys Asp Lys 1850 1855 1860Phe Pro
Glu Gly Thr Gly Val Thr Val Ala Asn Asp Gly Lys Ala 1865
1870 1875Thr Ile Thr Tyr Pro Asp Lys Ser Val Asp
Thr Ile Glu Gly Asn 1880 1885 1890Gln
Leu Val Glu Glu Lys Thr Ser Ala Glu Lys Leu Asp Pro Thr 1895
1900 1905Val Pro Ala Lys Thr Lys Val Asp Asn
Pro Thr Ser Leu Thr Ala 1910 1915
1920Asp Glu Lys Lys Thr Ile Glu Asp Lys Ile Val Glu Ala Asn Lys
1925 1930 1935Asp Lys Phe Pro Glu Gly
Thr Gly Val Thr Val Ala Asn Asp Gly 1940 1945
1950Lys Ala Thr Ile Thr Tyr Pro Asp Lys Ser Val Asp Thr Ile
Glu 1955 1960 1965Gly Asn Gln Leu Val
Glu Glu Lys Thr Ser Ala Glu Lys Leu Asp 1970 1975
1980Pro Thr Val Pro Ala Lys Thr Lys Val Asp Asn Pro Thr
Ser Leu 1985 1990 1995Thr Ala Asp Glu
Lys Lys Thr Ile Glu Asp Lys Ile Val Glu Ala 2000
2005 2010Asn Lys Asp Lys Phe Pro Glu Gly Thr Gly Val
Thr Val Ala Asn 2015 2020 2025Asp Gly
Lys Ala Thr Ile Thr Tyr Pro Asp Lys Ser Val Asp Thr 2030
2035 2040Ile Glu Gly Asn Gln Leu Val Glu Glu Lys
Thr Ser Ala Glu Lys 2045 2050 2055Leu
Asp Pro Thr Val Pro Ala Lys Thr Lys Val Asp Asn Pro Thr 2060
2065 2070Ser Leu Thr Ala Asp Glu Lys Lys Thr
Ile Glu Asp Lys Ile Val 2075 2080
2085Glu Ala Asn Lys Asp Lys Phe Pro Glu Gly Thr Gly Val Thr Val
2090 2095 2100Ala Asn Asp Gly Lys Ala
Thr Ile Thr Tyr Pro Asp Lys Ser Val 2105 2110
2115Asp Thr Ile Glu Gly Asn Gln Leu Val Glu Glu Lys Thr Ser
Ala 2120 2125 2130Glu Lys Leu Asp Pro
Thr Val Pro Ala Lys Thr Lys Val Asp Asn 2135 2140
2145Pro Thr Ser Leu Thr Ala Asp Glu Lys Lys Thr Ile Glu
Asp Lys 2150 2155 2160Ile Val Glu Ala
Asn Lys Asp Lys Phe Pro Glu Gly Thr Gly Val 2165
2170 2175Thr Val Ala Asn Asp Gly Lys Ala Thr Ile Thr
Tyr Pro Asp Lys 2180 2185 2190Ser Val
Asp Thr Ile Glu Gly Asn Gln Leu Val Glu Glu Lys Thr 2195
2200 2205Ser Ala Glu Lys Leu Asp Pro Thr Val Pro
Ala Lys Thr Lys Val 2210 2215 2220Asp
Asp Pro Thr Lys Leu Thr Asn Asp Glu Lys Lys Glu Val Glu 2225
2230 2235Asp Asn Ile Arg Asp His Asn Thr Gly
Leu Pro Glu Gly Thr Lys 2240 2245
2250Ile Ala Val Gly Asp Asn Gly Asp Thr Thr Ile Thr Tyr Pro Asp
2255 2260 2265Lys Ser Val Asp Thr Ile
Glu Gly Asn Gln Leu Val Glu Glu Lys 2270 2275
2280Thr Ser Ala Glu Lys Leu Asp Pro Thr Val Pro Ala Lys Thr
Lys 2285 2290 2295Val Asp Asp Pro Thr
Lys Leu Thr Asn Asp Glu Lys Lys Glu Val 2300 2305
2310Glu Asp Asn Ile Arg Asp His Asn Thr Gly Leu Pro Glu
Gly Thr 2315 2320 2325Lys Ile Ala Val
Gly Asp Asn Gly Asp Thr Thr Ile Thr Tyr Pro 2330
2335 2340Asp Asn Ser Val Asp Thr Ile Pro Gly Asp Lys
Val Val Glu Gly 2345 2350 2355Lys Ser
Asp Ala Ala Lys Asn Glu Pro Lys Val Pro Gly Asp Lys 2360
2365 2370Val Lys Val Asp Asp Pro Asn Lys Leu Thr
Glu Asp Glu Lys Ser 2375 2380 2385Glu
Val Val Lys Ala Val Glu Asp Ala Asn Lys Asp Glu Asn Gly 2390
2395 2400Lys Ser Thr Leu Pro Glu Gly Ser Lys
Val Thr Val Gly Asp Asn 2405 2410
2415Gly Asp Val Thr Val Thr Tyr Pro Asp Gly Ser Lys Asp Thr Ile
2420 2425 2430Pro Gly Asp Lys Val Val
Glu Gly Lys Gly Thr Glu Gly Gln Thr 2435 2440
2445Asp Ala Asp Lys Asn Glu Pro Lys Val Pro Gly Asp Lys Val
Lys 2450 2455 2460Val Asp Asp Pro Asn
Lys Leu Thr Glu Asp Glu Lys Ser Glu Val 2465 2470
2475Val Lys Ala Val Glu Asp Ala Asn Lys Asp Glu Asn Gly
Lys Ser 2480 2485 2490Thr Leu Pro Glu
Gly Ser Lys Val Thr Val Gly Asp Asn Gly Asp 2495
2500 2505Val Thr Val Thr Tyr Pro Asp Gly Ser Lys Asp
Thr Ile Pro Gly 2510 2515 2520Asp Lys
Val Val Glu Gly Lys Gly Thr Glu Gly Gln Thr Asp Ala 2525
2530 2535Asp Lys Asn Glu Pro Lys Val Pro Gly Asp
Lys Val Lys Val Asp 2540 2545 2550Asp
Pro Asn Lys Leu Thr Glu Asp Glu Lys Ser Glu Val Val Lys 2555
2560 2565Ala Val Glu Asp Ala Asn Lys Asp Glu
Asn Gly Lys Ser Thr Leu 2570 2575
2580Pro Glu Gly Ser Lys Val Thr Val Gly Asp Asn Gly Asp Val Thr
2585 2590 2595Val Thr Tyr Pro Asp Gly
Ser Lys Asp Thr Ile Pro Gly Asp Lys 2600 2605
2610Val Val Glu Gly Arg Gly Thr Glu Gly Gln Thr Asp Ala Asp
Lys 2615 2620 2625Asn Glu Pro Lys Val
Pro Gly Asp Lys Val Lys Val Asp Asp Pro 2630 2635
2640Thr Lys Leu Thr Glu Asp Glu Lys Ser Asp Val Glu Gln
Ala Ile 2645 2650 2655Lys Asp Ala Asn
Lys Asp Glu Asn Gly Lys Ser Thr Leu Pro Glu 2660
2665 2670Gly Ser Lys Val Thr Val Gly Asp Asn Asp Asp
Val Thr Val Thr 2675 2680 2685Tyr Pro
Asp Gly Ser Lys Asp Thr Ile Pro Gly Asp Lys Val Val 2690
2695 2700Glu Gly Lys Gly Thr Glu Gly Gln Thr Asp
Ala Asp Lys Asn Glu 2705 2710 2715Pro
Lys Val Pro Gly Asp Lys Val Lys Val Asp Asp Pro Asn Lys 2720
2725 2730Leu Met Glu Asp Glu Lys Ser Asp Val
Glu Gln Ala Ile Lys Asp 2735 2740
2745Ala Asn Lys Asp Glu Asn Gly Lys Ser Thr Leu Pro Glu Gly Ser
2750 2755 2760Lys Val Thr Val Ser Asp
Asn Gly Asp Val Thr Ile Thr Tyr Pro 2765 2770
2775Asp Gly Ser Lys Asp Thr Ile Pro Gly Asp Gln Val Ile Glu
Gly 2780 2785 2790Lys Ser Asp Ala Asp
Lys Asn Thr Pro Asn Val Pro Gly Gly Asp 2795 2800
2805Lys Val Lys Val Asp Asp Pro Thr Lys Leu Thr Asp Asn
Glu Lys 2810 2815 2820Asn Ala Val Lys
Asp Lys Val Asp Glu Ala Asn Ser Asn Leu Pro 2825
2830 2835Asp Gly Thr Lys Val Thr Val Gly Asp Asp Gly
Thr Thr Thr Ile 2840 2845 2850Thr Tyr
Pro Asp Gly Ser Thr Asn Thr Ile Ser Gly His Asp Leu 2855
2860 2865Val Thr Gly Lys Thr Asp Ala Asp Lys Tyr
Pro Leu Asn Pro Gly 2870 2875 2880Gln
Ala Val Asn Val Val Asp Pro Asn His Leu Thr Gln Ala Glu 2885
2890 2895Gln Asp Gln Val Lys Glu Ala Ile Gln
Thr Thr Asn Pro Thr Ala 2900 2905
2910Pro Ile Ala Thr Ile Thr Val Asp Thr Ala Gly Asn Val Gln Val
2915 2920 2925Thr Phe Ala Asp Gly Ser
Thr Thr Thr Leu Gln Ala Asn Leu His 2930 2935
2940Lys His Val Thr Glu Ala Thr Thr Gly Ser Ala Ile Lys Pro
Gly 2945 2950 2955Val Gly Thr Asn Gly
Gly Gln Thr Lys Gly Ala Thr Ser Thr Asn 2960 2965
2970Gln Thr Ala Thr Lys Gln Gln Ala Gln Gln His Leu Pro
Gln Thr 2975 2980 2985Gly Asp Gln Pro
Ala Thr Trp Ala Met Leu Ser Gly Leu Gly Val 2990
2995 3000Ala Phe Leu Gly Leu Leu Gly Leu Lys Lys Lys
Arg Glu Asp 3005 3010
3015161472PRTArtificial SequenceBased on Lactobacillus reuteri sequence
16Met Glu Ile Lys Lys His Phe Lys Leu Tyr Lys Asp Gly Lys Lys Trp1
5 10 15Cys Cys Ala Ala Ile Ala
Thr Thr Val Leu Gly Ile Gly Leu Ala Ile 20 25
30Gly Ser Pro Ser Val Leu Ala Asp Ala Asp Thr Ile Thr
Ser Thr Ser 35 40 45Asp Ala Asn
Asn Ser Leu Val Lys Asn Asp Asn Thr Ser Asp Thr Asp 50
55 60Ser Asn Ser Glu Ser Thr Phe Thr Asp Thr Asn Lys
Asn Ser Thr Asn65 70 75
80Glu Lys Glu Ile Asn Glu Asn Lys Asn Ile Asp Ser Ser Gln Gln Ile
85 90 95Asn Gln Glu Gln Thr Lys
Ser Asn Asn Ser Glu Glu Gln Thr Thr Pro 100
105 110Val Asn Val Lys Ala Glu Asn Thr Asp Ile Lys Asp
Ser Ile Pro Glu 115 120 125Lys Ser
Thr Pro Asn Ser Phe Lys Glu Ile Asn Gly Ser Thr Tyr Tyr 130
135 140Tyr Gly Glu Asn Gly Asp Leu Tyr Arg Asn Gln
Phe Tyr Asn Asn Trp145 150 155
160Gly Arg Thr Tyr Tyr Phe Gln Ala Asn Gly Ala Arg Leu Asp Asn Gly
165 170 175Phe Tyr Asn Asn
Trp Gly Arg Thr Tyr Tyr Phe Gly Ser Asp Gly Ala 180
185 190Arg Trp Asp Asn Arg Phe Tyr Asn Asn Trp Gly
Arg Thr Tyr Tyr Phe 195 200 205Gln
Asn Asp Gly Ser Arg Leu Asp Asn Ser Phe Tyr Asn Asn Trp Gly 210
215 220Arg Thr Tyr Tyr Phe Gly Val Asp Gly Ala
Arg Trp Asp Asn Arg Tyr225 230 235
240Met Val Lys Trp Gly Arg Ala Tyr Tyr Phe Gly Asn Asp Gly Ala
Leu 245 250 255Leu Gln Asn
Gln Leu Lys Ser Ile Asn Gly Ile Asn Tyr Trp Ile Asn 260
265 270Asn Glu Gly Ile Ile Pro Leu Lys Asn Gln
Phe Leu Thr Ala Asn Glu 275 280
285Asn Gln Leu Phe Tyr Phe Asp Gly Asn Gly Ser Leu Val Val Asn Lys 290
295 300Phe Tyr His Asn Trp Gly His Thr
Tyr Tyr Phe Gly Ser Asp Gly Ala305 310
315 320Arg Tyr Thr Asp Gln Phe Leu Asn Arg Asp Gly Lys
Val Tyr Tyr Phe 325 330
335Asp Asn Gln Gly Ile Met Tyr Gln Asp Gln Tyr Tyr Lys Asn Trp Gly
340 345 350His Thr Tyr Tyr Phe Gly
Ser Asp Gly Ala Arg Tyr Thr Asp Gln Phe 355 360
365Leu Asn Arg Asp Gly Lys Val Tyr Tyr Phe Asp Asn Gln Gly
Ile Met 370 375 380Tyr Gln Asp Gln Tyr
Tyr Lys Asn Trp Gly His Thr Tyr Tyr Phe Gly385 390
395 400Ser Asp Gly Ala Arg Tyr Thr Asp Gln Phe
Leu Asn Arg Asp Gly Lys 405 410
415Val Tyr Tyr Phe Asp Asn Gln Gly Ile Met Tyr Gln Asp Gln Tyr Tyr
420 425 430Lys Asn Trp Gly His
Thr Tyr Tyr Phe Gly Ser Asp Gly Ala Arg Tyr 435
440 445Thr Asp Gln Phe Leu Asn Arg Asp Gly Lys Val Tyr
Tyr Phe Asp Asn 450 455 460Gln Gly Ile
Met Val Thr Asn Gln Val Arg Val Ile Asp Gly Lys Gly465
470 475 480Tyr Glu Phe Asn Asp Asn Gly
Glu Ala Thr Glu Thr Ser Asp Met Gly 485
490 495Gln Thr Arg Asp Thr Val Ala Lys Glu Val Ala Gln
Ala Leu Thr Asn 500 505 510Gln
Gly Ile Lys Gly Val Lys Tyr Asp Trp Arg Asn Thr Asn Asn Asp 515
520 525Tyr Gln Glu Leu Ala Leu His Asp Ile
Ala Gln Glu Val Ala Gln Gly 530 535
540Asp Thr Asn Pro Asp Lys Asn Val Ile Glu Lys Lys Leu Gln Ala Asn545
550 555 560Asn Leu Leu Ser
Gly Lys Val Leu Val Val Tyr Ser Thr Asp Phe Thr 565
570 575Asn Asp Asp Pro Gln Lys Ile Thr Asn Thr
Phe Met Asn Ser Tyr Asp 580 585
590Phe Thr Asn Ala Asp Asn Ser Val Leu Gly Val Gly Ala Asp Leu Asn
595 600 605Lys Asn Lys Leu Val Ile Ile
Leu Phe Lys Pro Gly Glu Lys Ala Glu 610 615
620Gln Pro Gln Ala Thr Ser Thr Ile Ser Ala Ser Ile Ser Asp Ile
Phe625 630 635 640Lys Lys
Ala Gly Val Asn Val Asp Val Asp Asn Gly Leu Thr Lys Gly
645 650 655Ser Val Val Asn Ser Ala Asp
Leu Gly Asn Ala Leu Thr Asn Gly Thr 660 665
670Ala Glu Leu Leu Lys Gly Asp Lys Gly Thr Ile Ile Ser Gln
Glu Val 675 680 685Leu Lys Ala Ile
Phe Ala Ala Phe Ala Gly Asn Thr Ser Ala Val Glu 690
695 700Gly Thr Lys Asn Tyr Tyr Asn Gly Asn Asp Ala Tyr
His Tyr Glu Phe705 710 715
720Trp Leu Glu Gly Gln Ser Ala Asp Asp Lys Leu Asn Asn Phe Leu Ala
725 730 735Leu Asn Lys Gly Ala
Lys Tyr Gly Asp Gln Leu Lys Val Asn Tyr Thr 740
745 750Ala Thr Leu Val Phe Gly Gln Glu Thr Gly Thr Asn
Ser Asn Glu Ser 755 760 765Lys Val
Pro Ala Ser Glu Arg Thr Asp Glu Gln Leu Asp Leu Ala Tyr 770
775 780Lys Thr Gly Thr Asp Thr Gly Leu Arg Tyr Asp
Ser Val Lys Val Glu785 790 795
800Lys Ile Pro Gly Met Thr Asp Asp Met Val Arg Gly Val Asp Val Ser
805 810 815Ser Tyr Gln Ala
Leu Ile Asn Ala Gly Val Lys Phe Tyr Asp Phe Asn 820
825 830Gly Gln Glu Ser Asn Leu Phe Lys Ile Leu Lys
Asp Ser Gly Val Asn 835 840 845Trp
Val Arg Leu Arg Val Trp Asn Asp Pro Tyr Asn Ala Gln Gly Gln 850
855 860Pro Tyr Ala Gly Gly Asp Asn Asn Glu Glu
Asn Leu Ile Lys Met Ala865 870 875
880Lys Glu Ala Ser Asp Asn Gly Leu Lys Leu Leu Ile Asp Phe Gln
Tyr 885 890 895Ser Asp Phe
Trp Thr Asp Pro Ala Gln Gln Ile Leu Pro Lys Ala Trp 900
905 910Arg Asn Leu Ser His Gly Glu Met Ser Gln
Glu Val Tyr Leu Tyr Thr 915 920
925Ser Lys Ile Leu Asn Asp Leu Gln Lys Ala Gly Ala Ser Val Lys Met 930
935 940Val Gln Ile Gly Asn Glu Ile Thr
Asn Gly Ala Phe Gly Leu Tyr Thr945 950
955 960Gly Arg Asn Gly Gly Gly Asn Trp Ala Ser Leu Trp
Glu Thr Ser Asp 965 970
975Gly Asp Gln Val Ala Lys Tyr Ile Gln Ala Gly Ser Ser Ala Val Arg
980 985 990Arg Ile Asp Pro Thr Ile
Lys Val Ala Ile Gln Leu Glu Thr Pro Glu 995 1000
1005Ile Asn Lys Tyr Arg Gly Ile Met Asn Val Leu Lys
Lys Asn Asn 1010 1015 1020Val Asp Tyr
Asp Tyr Leu Gly Thr Ser Tyr Tyr Pro Phe Trp Ser 1025
1030 1035Thr Thr Gln Gly Asn Gly Trp Tyr Asp Asn Val
Asp Leu Gly Tyr 1040 1045 1050Gly Ala
Asn Thr Pro Val Asn Leu Glu Ala Ile Glu Lys Met Ala 1055
1060 1065Trp Asn Glu Phe Gly Lys Arg Thr Val Ile
Leu Glu Ser Gly Trp 1070 1075 1080Leu
Asn Asn Thr Asn Asp Ala Asp Gly Thr His Asn Ser Val Gly 1085
1090 1095Glu Asn Asn Glu Thr Thr Asn Ile Asp
Arg Tyr Ser Ala Asp Pro 1100 1105
1110Gln Gly Gln Val Asp Glu Ile Glu Asp Met Tyr Asn Ala Ile Ile
1115 1120 1125Ala Gln Lys Gly Leu Gly
Ala Phe Tyr Trp Glu Pro Ala Trp Ile 1130 1135
1140Pro Val Lys Ala Gly Trp Asn Asn Trp Gln Tyr Asn Lys Leu
Met 1145 1150 1155Ser Asn Ile Tyr Gly
Ser Gly Trp Ala Ser Gln Tyr Ala Lys Gly 1160 1165
1170Tyr Ala Pro Asp Ser Val Leu Tyr Tyr Asp Gly Lys Glu
Ala Trp 1175 1180 1185Gly Gly Ser Ser
Trp Asp Asn Ile Ser Leu Phe Asp Asp His Gly 1190
1195 1200His Pro Leu Gln Ser Leu Asn Val Tyr Asn Gly
Met Leu Asn Gly 1205 1210 1215Tyr Glu
Ser Pro Lys Asn Val Lys Ser Ser Leu Ser Thr Gln Leu 1220
1225 1230Val Lys Ile Trp Asn Glu Thr Asp Val Ile
Pro Asn Asp Gly Leu 1235 1240 1245Thr
Glu Gly Thr Lys Leu Ser Thr Asp Leu Phe Gly Thr Thr Gln 1250
1255 1260Leu Ser Gly Asn Asp Gly Gln Ser Ile
Gly Asn Ala Glu Leu Thr 1265 1270
1275Lys Leu Ala Gly Arg Leu Lys Asp Gly Ile Ser Ser Lys Val Tyr
1280 1285 1290Thr Ala Ala Asn Gly Ala
Arg Tyr His Tyr Ile Tyr Trp Leu Glu 1295 1300
1305Gly Gly Asn Asn Lys Val Asn Thr Phe Val Ser Ala Asn Lys
Asp 1310 1315 1320Ala Lys Tyr Gly Gln
Pro Leu Ile Ala Asn Tyr Ser Ala Thr Val 1325 1330
1335Val Val Asp Ser Glu Pro Gly Thr Gln Val Ala Thr Ser
Pro Leu 1340 1345 1350Gln Ile Lys Ile
Ser Gln Val Trp Asn Thr Val Asn Asn Glu Glu 1355
1360 1365Ile Lys Ile Asp Asn Pro Leu Lys Gln Gly Asp
Leu Ile Thr Asp 1370 1375 1380Lys Ser
Asp Asn Ala Phe Ser Gly Ile Leu Asn Ser Lys Asp Ile 1385
1390 1395Lys Glu Ala Leu Thr Gly Glu Lys Gly Lys
Asp Val Ser Glu Ser 1400 1405 1410Thr
Val Asn Asp Val Lys Ser Leu Leu Pro Lys Glu Val Lys Gly 1415
1420 1425Ser Lys Thr Tyr Thr Thr Ala Asp Gly
Asn Gln Tyr Tyr Tyr Asp 1430 1435
1440Phe Trp Leu Ala Ser Val Glu Thr Ser Asn Val Asn Tyr Gly Glu
1445 1450 1455Pro Ile Ile Val Asn Tyr
Thr Ala Ser Leu Lys Trp Leu Gly 1460 1465
1470171063PRTArtificial SequenceBased on Lactobacillus reuteri
sequence 17Met Glu Lys Thr Met Lys Lys Lys Ala Leu Val Ala Thr Thr Ala
Val1 5 10 15Ala Gly Ile
Thr Leu Val Gly Glu Val Thr Thr Val His Ala Ala Asp 20
25 30Asn Val Gln Gln Pro Val Asn Glu Gln Asn
Val Asn Gln Ser Ser Gln 35 40
45Glu Glu Lys Gln Ala Ala Gln Asn Leu Gln Asn Ala Gln Ser Asp Val 50
55 60Asn Thr Ala Thr Glu Ala Asn Ser Asn
Ala Gln Asp Asn Leu Ala Ser65 70 75
80Ala Asn Asn Asn Leu Ser Asn Ala Lys Lys Ala Val Ser Asp
Gln Ala 85 90 95Ala Lys
Val Ala Asp Ala Thr Lys Ala Gln Ser Asp Ala Ser Thr Lys 100
105 110Val Asp Asn Asp Asn Lys Val Val Ala
Asp Ala Gln Gln Lys Ala Asp 115 120
125Gln Ala Thr Pro Ala Asn Ile Glu Asn Ala Lys Gln Ala Ile Glu Gly
130 135 140Gln Asn Lys Val Ile Asp Gln
Asp Asn Glu Asn Ile Lys Tyr Ser Asn145 150
155 160Thr Asp Gln Asp Lys Ala Gln Asn Thr Leu Asn Asn
Ala Gln Ser Asn 165 170
175Glu Asp Lys Ala Asn Ala Thr Leu Ser Asn Lys Lys Ser Ser Gln Ala
180 185 190Ser Ala Gln Asn Asn Val
Lys Gln Ala Glu Asp Ala Leu Asn Gly Thr 195 200
205His Leu Val Glu Ala Gln Asn Ala Phe Asn Gln Ala Gln Ser
Asn Val 210 215 220Glu Asn Ala Gln Ser
Lys Tyr Asp Gln Ala Asn Asn Gln Leu Ser Asp225 230
235 240Ala Gln Lys Lys Val Thr Thr Asn Gln Asn
Asp Leu Thr Ala Lys Asn 245 250
255Lys Ala Leu Asp Asn Ile Asn Asn Gln Val Asp Thr Asp Gln Asn Asn
260 265 270Val Asn Ser Asn Gln
Ala Thr Ala Asp Ser Ala Ser Ser Ala Thr Gln 275
280 285Val Ala Gln Asn Ala Val Asp Gln Thr Lys Gln Ser
Leu Asp Lys Val 290 295 300Ile Glu Glu
Leu Asn Gly Phe Ser Glu Asn Thr Ile Lys Val Pro Ala305
310 315 320Gly Ala Gln Glu Ala Tyr Glu
Ala Phe Ile Asp Ala Val Asp Asn Asn 325
330 335Ala Asp Gln Ser Gln Leu Asp Ser Leu Ala Lys Lys
Met Tyr Asp Thr 340 345 350Leu
His Gln Gly Gln Gly Thr Asn Gly Ile Asn His Phe Asn Ser Ser 355
360 365Lys Tyr Asp Gln Asn Gln Leu Val Asp
Val Asp His Leu Thr Thr Asp 370 375
380Gln Leu Asn Glu Leu Thr Gln Phe Ala Ala Asp Met Ile Asn Ser Ala385
390 395 400Arg Lys Ala Trp
Gly Ser Asp Lys Asn Ala Gly Thr Leu Ile Pro Thr 405
410 415Gln Gly Val Ser Glu Met Ala Gln Gln Ile
Ala Lys Gly Tyr Val Ser 420 425
430Asp Asn Trp His Ile Ser Gln Gly His Asp Val Lys Arg Val Thr Ala
435 440 445Ala Ala Gly Leu Ile Gly Leu
Asn Asp Ala Gly Gln Phe Tyr Glu Asp 450 455
460Ala Ser Glu Gly Tyr Val His Ala Trp Pro Trp Glu Lys Asp Ser
Tyr465 470 475 480Thr Met
Asp Asn Leu Lys Glu Ala Val Tyr Asp Ser Ile Leu Gly Met
485 490 495Leu Phe Ala Asp Asp Asn Ser
Gly Asn Gly His Met Thr Asp Leu Leu 500 505
510Gly Leu His Val Asn Arg Lys Glu Asp His Gln Tyr Phe Gly
Leu Ser 515 520 525Thr Asn Met Cys
Pro Gly Ser Tyr Met Gly Gln Leu His Phe Ile Ile 530
535 540Val Glu Asn Asp Pro Ala Tyr Ile Lys Asp Pro Gln
Thr Phe Asn Ala545 550 555
560Lys Gly Gly Thr Thr Lys Ile Glu Tyr Ile Asp Pro Lys Val Gln Leu
565 570 575Asn Gln Gln Lys Asp
Ile Leu Thr Thr Thr Leu Ser Thr Gln Gln Ala 580
585 590Asp Leu Ala Thr Lys Gln Asp Ala Leu Asn Lys Ala
Asn Gln Asn Leu 595 600 605Ala Asn
Ala Lys Lys Gln Leu Ser Glu Asp Gln Asp Leu Gln Thr Val 610
615 620Ala Gln Gln Asn Arg Asp Ser Ala Gln Lys Ala
Leu Asn Asp Ala Thr625 630 635
640Ala Lys Val Ser Asn Leu Gln Ala Thr Val Asn Ser Leu Ser Gln Asp
645 650 655Leu Asn Ser Ala
Lys Ala Thr Leu Asp Gln Ala Lys Lys Thr Leu Glu 660
665 670Ser Tyr Thr Ala Asp His Lys Ala Lys Leu Asp
Asn Tyr Asn Asn Ala 675 680 685Lys
Ala Ala Leu Asp Asp Ala Asn Lys Ala Val Ala Glu Ala Gln Ser 690
695 700Ala Val Asp Thr Ala Val Asn Glu Thr Lys
Ile Ala Gln Asn Asn Leu705 710 715
720Asp Gln Lys Lys Gln Ala Val Thr Asp Ala Gln Asn Lys Leu Ala
Asn 725 730 735Asp Gln Glu
Tyr Leu Ala Thr Leu Lys Gln Asn Leu Ala Asp Leu Gln 740
745 750Asn Ala Pro Gln Asn Leu Gln Lys Ala Lys
Asp Gln Leu Ala Lys Asp 755 760
765Gln Ile Ala Leu Asp Asn Ala Asn Lys Asp Leu Gln Asn Gln Lys Asp 770
775 780Ser Leu Asp Glu Leu Asn Lys Lys
Leu Glu Asp Ala Gln Val Lys Val785 790
795 800Asn Glu Ala Gln Ser Ala Ala Asn Val Thr Lys Ala
Thr Leu Asp Gln 805 810
815Ala Gln Ala Lys Leu Ser Asp Ala Glu Ala Thr Trp Lys Glu Leu His
820 825 830Asn Asp Ala His Arg Tyr
Gly Asn Val Val Lys Val Thr Pro Ile Thr 835 840
845Met Glu Ala Gly Thr Ser Leu Pro Asp Pro Val Ile Glu Asn
Gly Phe 850 855 860Thr Val Asn Thr Gly
Thr Asn Gln Leu Phe Val Ser Leu Ala Ala Ile865 870
875 880Asp Ser Ser Asn Asn Asn Ile Pro Gln Gly
Thr Lys Ala Ser Trp Ala 885 890
895Asn Arg Ser Lys Ala Leu Thr Asp Ser Gln Asn Ala Gly Ser Tyr Ser
900 905 910Glu Asp Ile Leu Ile
Thr Phe Pro Asp Asn Ser Thr Val Thr Val Pro 915
920 925Val Asp Leu Thr Val Thr Ala Lys Lys Ile Thr Glu
Asp Gln Lys Ala 930 935 940Thr Glu Gly
Gly Tyr His Ile Val Asn Gly Ser Val Val Asp Lys Gln945
950 955 960Asn Asn Leu Val Ser Gly Trp
Thr Val Lys Asn Gly Gln Met Val Asp 965
970 975Pro Glu Gly Asn Val Ile Lys Thr Thr Met Ser Thr
Ala Gln Gly Val 980 985 990Thr
Ile Glu Lys Asn Asn Ser Lys Ser Gly Asn Thr Lys Thr Asn Met 995
1000 1005Ile Gln Thr Ser Leu Thr Ile Ala
Asn Asn Lys Ala Thr Thr Asn 1010 1015
1020Lys Asp Asn Gln Leu Pro Gln Thr Gly Asn Tyr Asn Asn Asn Thr
1025 1030 1035Lys Val Leu Gly Leu Ala
Gly Ile Ala Leu Ala Ser Ala Leu Thr 1040 1045
1050Met Phe Gly Tyr Lys Lys Arg Gln His Asn 1055
106018212PRTArtificial SequenceBased on Lactobacillus reuteri
sequence 18Met Lys Ser Thr Thr Lys Lys Ile Leu Ala Ser Ser Leu Gly Val
Ala1 5 10 15Gly Ala Met
Ala Met Gly Thr Val Thr Ala Lys Ala Asp Thr Thr Val 20
25 30Thr Val Asn Ala Gly Asp Ser Leu Asn Gly
Ile Ala Gln Lys Tyr Asn 35 40
45Val Ser Ala Asp Asp Ile Ala Thr Ala Asn His Leu Gln Asn Lys Glu 50
55 60Leu Ile Phe Val Gly Gln Lys Leu Thr
Ile Pro Thr Lys Asp Lys Asn65 70 75
80Glu Thr Pro Ala Asn Asn Ala Glu Lys Lys Asp Gln Ala Ser
Lys Asn 85 90 95Ser Gln
Ser Leu Gln Asp Ser Val Asn Lys Ala Met Ser Tyr Leu Gly 100
105 110Thr Pro Tyr Val Trp Gly Gly Asn Lys
Pro Gly Gly Phe Asp Cys Ser 115 120
125Gly Leu Val Gln Tyr Cys Tyr Gly Ile Pro Gln Arg Thr Thr Tyr Glu
130 135 140Gln Gln Ala Leu Gly Pro His
Ile His Asp Asn Val Leu Asn Ala Pro145 150
155 160Tyr Gly Ala Leu Val Phe Tyr Gly Ser Asp Asp Ala
Pro Tyr His Val 165 170
175Ala Ile Ser Leu Gly Asp Gly Arg Ile Ile Gln Ala Pro Asn Glu Asn
180 185 190Glu Thr Val Lys Ile Thr
Asp Gln Gln Tyr Phe Pro Gly Asn Tyr Tyr 195 200
205Val Val Met His 210191107DNAArtificial SequenceBased
on Lactobacillus reuteri sequence 19atgcgtaatc aattcatcga tgtttcaagt
tatcaaccag atactgttgc ctttttccaa 60gctgctaaag ctcagggtgc attaggggtc
gttgttaagt taacggaagg gtccgaagat 120ggttcggctt atgttaatcc acgtgcggcc
gctcaaattc gtaatgcctt agcggttggc 180ttgcgcgttt cctgttacca ctttgctcgt
tatacatcag tgactgatgc acaaaatgaa 240gctcgattct tcgttaaaat cgctaagcaa
tttggtatgt atgacgatac tttgatgatt 300gatgatgcgg aagttcattc aactgcagat
tatcaatcag tatccttagc ctttcttcaa 360gaagtagaag ctcttggtta caagaatact
gggatttact ccatgaagtc cttcttcact 420ggcggtattc ttaattcaca tggctttgat
tcccggaaga tttggattgc tggctatggt 480gtgactgaac tggggattga taatgcaagt
gcttggcaat attctgatca tagcatcatg 540ggaattgata ctagttatga ctttgacggt
gcctttacga ctggtttagt atcaggcaat 600gttccgcaag ctgttattcc agcaccacag
ccggttcaac atattggtca cccagctact 660ggaacctaca ttgttcagcc gggcgataca
ttgagtggaa ttgcagaaaa atacgggact 720acttatcaga acctagcagc aatcaatggt
attggtaatc caaaccagat caatgtcggc 780caagtcctca aagtcaccgg aaaagtatca
aacgaaaata cttactttgt tcaatcaggc 840gatacgttat ccggaattgc caccaaattc
ggcaccactg tctcagacct cgtaagccgt 900aatcacatta ctaacccgaa tgtgatctac
gttgggcaaa aactctactt agccggcaac 960ggacaatcca atgcttatac tgtccaagca
ggggacacac taagcggaat tgcggctaag 1020tttggcaaga cctggcaagc attagctcaa
aagaatggca tcgcaaatcc taatatgatt 1080ttcattggtc aaacaattca gatttaa
1107202439DNAArtificial SequenceBased on
Lactobacillus reuteri sequence 20gtgtaccgaa ttattggtta taatgaacca
acagataaag caggatttat tgtactggat 60ccccgagtta atcgtcatat tagttcggga
aaactcacgc ttaaagaatc taatattgat 120gatttgacta ttacggttaa tcaagcaagt
ccattatggg acaacgtaag gccttatcat 180actcatgtta acgtttatga tgataatgaa
cttatttttc gtggacgagc tatcaaacct 240aaaaagtcga tggaagaaag cggacaattc
attcgtgaat atgtttttga agatattgaa 300gcatatctca tggatagcac ccaaagattt
tatgaaggtg ttggtcaaac gcccaaagaa 360tttttacaaa ctttaatcga tgttcataat
tcacaggttc ctgactataa aaagtttcaa 420gtccggaatg taaatgtcac taataataag
gatgaccaat atcgacaaat tgattatccc 480aaaactagcg atgctattaa tgataaatta
gttaaatctc ttggtggtta tattgtgact 540acttacaacg ctaacggaat aaactacatt
gactacttaa cggatattgg ggttgatcat 600aaagatgata ctcctattca gttagctaaa
aatatgaagt ctgcaagtat gcaaattgat 660cctactaagg tgattacaag actgattcca
ctgggaaaga cactagaacc atcaaaagtt 720gatgtaagtg atgatgatgg agagggcggt
tctggatcat tagatagccc tgaagaattt 780tgtaaatcag aaattaatgc tacttggggt
agtgatatta ataatatgaa acaagatttt 840gccgctcgtt cttcgagagt tcgggcttgg
ggagtggacg ttaatcgttt atatgatgtg 900gtgaaaaatg ctggagtaag tcctgaatgg
ttctttgctt atgaacttca agaacaagga 960acttactatg gatggcttaa ccatacttat
cgacacggtg atgcgtatag tgatgcgcaa 1020tctgtttgtg agtggattaa aaattgttca
aatagtaatt ccattaatcc agcatggagc 1080gcaccggaag gatcaatggc gccgaatcaa
gcattagcgg ataaatggaa tcaagagttt 1140ggaaaaggta ctattggccg cgtttattta
caagggactg ccgctgctgt ttgggattta 1200gctggtcaaa cgcctaatcc agctattgga
aagccaatta gtggatgcat ttcttgtatt 1260aaacgttggg gtggtcattc taatgcagct
ggtggtacat ggggatggcc ttttcctgat 1320gttggggaag gtcatttttc tcaagttcag
agtttcggaa atgatggcgg atatcgtcaa 1380aatagttatc acgatggtgt ggattttgga
tcaatagatc atcctggtag agaagtgcat 1440tgtattcatg gtggaacggt aactatcaaa
tcagctatgg gtggcttagg taattttgtg 1500gttattcata cgccggaagg attcaatatc
gtttatcaag aagcttttag ttctccctct 1560aatattattg ttagtgttgg gcaaaaagta
aaaactggtg atgtaattgg atatcgtgat 1620acagaccatg ttcatattgg cgtaactaag
caagattttt atcaagcagt tcgaaattct 1680ttttctcctg caggtggttg gctagatcca
gtaaaactaa ttaaagaagg tggcgatggg 1740tctaaaccac aagaaggaaa gaaagatcaa
actgttgata atagtaatgc tgcacgtcct 1800aaattaacca ttactactgt caataacggt
agagactata ttgatattcc tgatttacaa 1860aaagaattcg gtattattga gggaactgtt
gaatttgata atgtagatga tccgaatgtt 1920ttaatgcaac aagctcaaac atggataaag
gctcaaagaa tacctcaaag ttgggaagtt 1980acagctttag aattacatat gacaaacttc
aaatctttta aggttgctga taggtacatg 2040tttattaatc caaatgttgc aaaaccccaa
ttattacgaa ttactcaaaa agaaattgat 2100ttactaaagc cccatgcgtc ttcattaacg
attggtgata agacgatggg gcttactgat 2160tatcagttag aaaatcaagt caattttcaa
caatttaagg aaattcgagt gatggttaat 2220caggttgtcc aaacccaaga gcaatctgct
aataacaata ataaggttat gcaaaatttt 2280gctagtagtg ctgatcttgc acaaatgaga
caggatctaa gaaatcttca agatgataac 2340gatcgtgctc gcaaaggaat ggtttcctta
gaagaattca ataaactaaa ggaacaagta 2400gaaaaactaa caacaggagg cgatgataat
ggcaagtga 243921739PRTArtificial SequenceBased
on Lactobacillus reuteri sequence 21Met Asn Lys Ala Asn Gln Lys Val Ala
Asp Asp Thr Thr Ala Val Asn1 5 10
15Asn Lys Gln Thr Asp Val Asn Asn Ala Ala Glu Ala Lys Lys Asn
Ala 20 25 30Asp Glu Ala Leu
Lys Asn Ala Asn Asp Ala Gln Thr Ser Ala Gln Lys 35
40 45Asn Lys Asp Ala Lys Gln Ala Ile Ala Asp Glu Ala
Ser Val Ala Leu 50 55 60Ala Asp Ala
Asn Thr Ala Val Lys Asp Ala Gln Ala Lys Val Asp Ala65 70
75 80Ile Asn Asp Lys Leu Ala Asn Phe
Asn Thr Ile Thr Leu Pro Ala Gly 85 90
95Tyr Lys Asp Asp Leu Ile Ala Tyr Tyr Asn Tyr Phe Gly Asn
Ser Asn 100 105 110Tyr Asn Gln
Asp Glu Ala Asn Asn Leu Ala Gln Asp Leu Leu Lys Tyr 115
120 125Arg Asp Gln Ala Met Ser Gln Asn Lys Phe Lys
Asp Asn Leu Ser Asp 130 135 140Asp Arg
Val Val Asp Ile Asp Asn Leu Asn Ser Thr Asp Arg Ala Glu145
150 155 160Leu Ser Gln Phe Val Ala Ser
Leu Ile Asn Gln Val Arg Thr Gln Met 165
170 175Gly Thr Asn Leu Val Ile Ser Ser Pro Ala Ala Asp
Asp Tyr Ala Glu 180 185 190Gln
Val Ser Gln Asn Tyr Asn Lys Asp Asn Trp Asn Ser Ala Asp Asn 195
200 205Gly Lys His Asp Gln Ser Ala Leu Asn
Asn Ala Thr Asp Gln Leu Asn 210 215
220Ile Ser Trp Asn Gly Glu Asn Met Gly Leu Asp Gln Ser Ile Phe Thr225
230 235 240Thr Asp Tyr Thr
Val Leu Thr Asp Gly Thr Lys Leu Pro Thr Gly Asn 245
250 255Lys Gln Thr Ile Asn Asp Leu Lys His Leu
Ile Tyr Asp Asp Phe Ile 260 265
270Ser Met Met Phe Asp Asp Ala Asp Ser Ala Trp Gly His Ala Thr Asn
275 280 285Phe Ala Gly Ile Asp Asn Phe
Ala Ala Glu Lys Gln Ala Val Gly Phe 290 295
300Ser Leu Asp Lys Phe Tyr Asn Thr His Tyr Asp Leu Val Glu Ala
Asn305 310 315 320Gln Lys
Val Glu Glu Asn Ser Tyr Thr Leu Pro Ser Ile Asn Ala Leu
325 330 335Thr Gln Lys Leu Ala Asp Ala
Lys Asp Asp Leu Ser Ile Lys Gln Thr 340 345
350Asp Gln Ala Ser Lys Gln Lys Ala Asn Asp Asp Ala Gln Asn
Ala Leu 355 360 365Ser Ser Ala Asn
Gln Val Leu Val Ala Ala Gln Asn Asp Val Lys Asp 370
375 380Lys Thr Ala Thr Ala Gln Glu Ala Asn Asp Asn Leu
Thr Thr Ala Gln385 390 395
400Asn Asp Leu Ala Thr Leu Gln Asn Gln Leu Ser Ala Asp Gln Ala Asn
405 410 415Gln Lys Gln Ala Gln
Thr Thr Phe Asp Ser Phe Asp Ala Asp Leu Ala 420
425 430Thr Lys Gln Ala Asn Leu Gln Lys Ala Thr Asp Ser
Leu Lys Ala Glu 435 440 445Gln Gly
Arg Leu Ala Ile Ala Gln Ala Asp Leu Asp Asn Ala Asn Lys 450
455 460Ala Leu Ser Asp Ala Asn Asn Asn Leu Ala Gln
Lys Lys Gln Val Val465 470 475
480Glu Asn Asp Asn Glu Thr Leu Lys Val Asp Asn Asp Lys Leu Val Gln
485 490 495Leu Gln Asn Asn
Leu Ser Asp Leu Gln Asn Ala Pro Lys Leu Leu Ala 500
505 510Ala Ala Lys Glu Gln Val Ala Thr Ala Gln Lys
Ala Leu Ala Asp Ala 515 520 525Gln
Glu Ala Tyr Asn Val Ala Asn Asp Lys Leu Thr Ser Leu Lys Gln 530
535 540Thr Ala Ala Gly Thr Thr Thr Asn Val Ser
Lys Ala Gln Gln Ala Leu545 550 555
560Ala Glu Ala Lys Asn Asn Glu Asp Ala Ala Lys Glu Val Leu Asp
Gln 565 570 575Ala Gln Gln
Ala Leu Thr Glu Leu Arg Gln Lys Glu Ala Leu Ala Lys 580
585 590Gln Val Ala Glu Glu Gln Ala Lys Leu Ala
Ala Glu Lys Glu Ala Lys 595 600
605Asp Asn Gly Tyr His Ile Glu Asn Asn Gln Val Val Asp Ala Lys Gly 610
615 620Asn Ser Val Asn Gly Trp Thr Val
Lys Gly Asn Gln Ile Val Ser Pro625 630
635 640Thr Asn Ala Thr Val Asp Pro Ala Val Ser Val Thr
Thr Asn Val Asn 645 650
655Val Asp Ser Lys Gly Gln Val Gln Pro Gln Thr Ser Val Thr Ala Asn
660 665 670Ser Val Lys Thr Val Ala
Ala Thr Glu Ser Ala Asn Pro Val Ala Thr 675 680
685Thr Thr Val Gln Thr Arg Glu Gln Tyr Lys Gln Gln Leu Lys
Ser Asn 690 695 700Asn Gln Leu Pro Gln
Thr Gly Asn Asn Asp Ser Ala Val Leu Ser Leu705 710
715 720Ala Gly Val Ala Leu Ala Ala Met Leu Ser
Leu Phe Gly Ile Lys Lys 725 730
735Arg Glu Tyr22185DNAArtificial SequenceBased on Lactobacillus
reuteri sequence 22aaattaaaag gctggatttt ttcggccttt ttttagtgca aataattatt
ttttacgtat 60ttatattata gggctaatca ctaaactaat aattagtggt tgaagcgctg
aaaattttct 120gctattttat taatagtttg ataataaaat aatgatattt aatataaaga
gggataaacg 180aaata
18523275DNAArtificial SequenceBased on Lactobacillus reuteri
sequence 23gaagtacaaa gttactttaa ctataatgaa aaacaagaca atataaagaa
aacaacatat 60aaggttcagt tcataactga ttagatttat aataaatatt gtaaatcgga
caaaaataaa 120ttaattttca attaattcaa aaaaaccata tttttttcgt tttggcatat
ttggatttgc 180tacactaaag atgatcaaga aaggggaaaa gataatcttc aatcttgtgt
acttagtttg 240ttaattaatt tataaattta gggaggaaac ctatc
27524313DNAArtificial SequenceBased on Lactobacillus reuteri
sequence 24gcaatgcaca agatgctgaa acaaaggcac aacaaaatgc agatcaagct
tcaccagcta 60atattcaaaa ggcacaagat gctattgcta atcaagaaac tcaaattagt
aaagacaccg 120atgctattaa tgacgctaac aaagccgtta gcgatgcaca aagcacagtt
gatgcagcgc 180aaaaaaagtt aatgatgcaa ctactgctcg tgacaatcaa caaaagaatg
ttgatactgc 240tagtgatgca gttaagaatg ctcaagctat tcttgacaac agtgatcagg
ctaaaaagga 300agcccaagat gct
31325527DNAArtificial SequenceBased on Lactobacillus reuteri
sequence 25gccgcgggtg cctatacatg cagtcgtacg cactggccca actgattgat
ggtgcttgca 60cctgattgac gatggatcac cagtgagtgg cggacgggtg agtaacacgt
aggtaacctg 120ccccggagcg ggggataaca tttggaaaca gatgctaata ccgcataaca
acaaaagcca 180catggctttt gtttgaaaga tggctttggc tatcactctg ggatggacct
gcggtgcatt 240agctagttgg taaggtaacg gcttaccaag gcgatgatgc atagccgagt
tgagagactg 300atcggccaca atggaactga gacacggtcc atactcctac gggaggcagc
agtagggaat 360cttccacaat gggcgcaagc ctgatggagc aacaccgcgt gagtgaagaa
gggtttcggc 420tcgtaaagct ctgttgttgg agaagaacgt gcgtgagagt aactgttcac
gcagtgacgg 480tatccaacca gaaagtcacg gctaactacg ccccccacca gccccaa
52726531DNAArtificial SequenceBased on Lactobacillus reuteri
sequence 26tgctggggtt tgcctataca tgcagtcgta cgcactggcc caactgattg
atggtgcttg 60cacctgattg acgatggatc accagtgagt ggcggacggg tgagtaacac
gtaggtaacc 120tgccccggag cgggggataa catttggaaa cagatgctaa taccgcataa
caacaaaagc 180cacatggctt ttgtttgaaa gatggctttg gctatcactc tgggatggac
ctgcggtgca 240ttagctagtt ggtaaggtaa cggcttacca aggcgatgat gcatagccga
gttgagagac 300tgatcggcca caatggaact gagacacggt ccatactcct acgggaggca
gcagtaggga 360atcttccaca atgggcgcaa gcctgatgga gcaacaccgc gtgagtgaag
aagggtttcg 420gctcgtaaag ctctgttgtt ggagaagaac gtgcgtgaga gtaactgttc
acgcagtgac 480ggtatccaac cagaaagtca cgactaacta cgccccacac cccagccgca a
53127165DNAArtificial SequenceBased on Lactobacillus reuteri
27atggatatga aaataaaaaa agaaccacca caacaagtaa aattagttga agtaattcag
60gttataacct ctcgtggagc tggaacaaag gaggatccga taagaaagat tattcagtat
120tggagcaaag aaggcacatt attagcagaa agttttggaa actaa
16528129DNAArtificial SequenceBased on Lactobacillus reuteri 28atggctggta
tcaaaagtat cgcaaaagcg gtaatgaccc agaatcactt cgtgatcgcc 60gaggcaaagc
taagccagaa gagaagtgga cggaagttga ccgactcaag gcagaaaatc 120gcttattaa
12929117DNAArtificial SequenceBased on Lactobacillus reuteri 29atggctaaat
acactgttga attaagtgaa gaagatatcc aaatgatcaa ggattgtcat 60tcaaagaatc
cttctatcat gaaggcaatg aacgacgcta aaaaagttga agattaa
117306789DNAArtificial SequenceBased on Lactobacillus reuteri
30gtggatgcgg attcgctggc actcgttgat gcactttcac ttgcgctcgt tgatgccgat
60tcactggcac tcgttgatgc actttcgcta gcactagtag aagctgactc acttgcactt
120gtcgatgccg attcgcttgc acttgtcgat gctgattcgc ttgcgctcgt tgaggctgat
180tcgctagcac tagtagaagc tgattcactg gcactcgttg aggcactttc acttgcgctt
240gttgaagccg actcacttgc gctcgttgat gcactttcgc tggcacttgt cgatgccgat
300tcacttacgc tcgttgaggc cgattcgctg acactcgttg atgcactttc acttacgctc
360gttgaggccg attcgctgac actcgttgat gcactttcac ttacgctcgt tgaggccgat
420tcgctgacac tcgttgatgc actttcgctg gcacttgtcg aggcactttc acttacgctc
480gttgaggccg attcacttac gctcgttgag gccgattcac ttgcgcttgt ggatgcggac
540tcacttgcac tcgttgaggc actttcactt gcacttgtcg atgcagattc gctggcactc
600gttgatgcac tttcacttgc actcgttgat gcactttcac ttgcacttgt cgatgcggat
660tcacttgcac ttgttgaagc ggattcgcta gcacttgtcg atgcggattc acttgcgctt
720gttgaagcgg attcgctggc gcttgttgaa gccgactcac ttgcactcgt tgaggctgat
780tcacttgcac tcgttgaggc actttcgctg gcgctcgttg atgcagattc gctggcactc
840gttgaggccg attcgctggc gcttgttgag gccgattcgc ttgcacttgt cgatgctgat
900tcacttgcac tggttgaagc agattcgctg gcactcgttg aggcactttc gctggcactc
960gttgaggccg attcacttgc gcttgttgaa gctgattcac ttgcacttgt cgatgctgat
1020tcacttgcgc tagtagatgc cgattcgctg gcactcgttg aagcagattc acttgcgctt
1080gttgaagccg attcacttgc gcttgttgaa gccgactcac ttgcactcgt tgaggcactt
1140tcgctggcgc tcgttgaagc agattcgctg gcactcgttg aagcagattc gctggcgctt
1200gttgaggccg attcgcttgc acttgtcgat gctgattcac ttgcactggt tgaagcagat
1260tcgctggcac tcgttgaggc actttcgctg gcactcgttg aggccgattc acttgcgctt
1320gttgaagctg attcacttgc acttgtcgat gctgattcac ttgcgctagt agatgccgat
1380tcgctggcac tagtagaagc agattcactt gcgcttgttg aagccgattc acttgcgctt
1440gttgaagccg actcacttgc actcgttgat gccgattcac ttgcacttgt ggatgcggac
1500tcacttgcac tcgttgatgc actttcactt gcacttgtgg atgcggattc gctggcactc
1560gttgatgcac tttcacttgc gctcgttgat gccgattcac tggcactcgt tgatgcactt
1620tcgctagcac tagtagaagc tgactcactt gcacttgtcg atgccgattc gcttgcactt
1680gtcgatgctg attcgcttgc gctcgttgag gctgattcgc tagcactagt agaagctgat
1740tcactggcac tcgttgaggc actttcactt gcgcttgttg aagccgactc acttgcgctc
1800gttgatgccg attcactggc actcgttgag gcactttcac ttgcgcttgt tgaagccgac
1860tcacttgcgc tcgttgatgc actttcgctg gcacttgtcg atgccgattc acttgcgctt
1920gtggatgcgg actcacttgc actcgttgaa gccgattggc ttgcactagt agaagctgat
1980tcactggcgc tcgttgaggc tgattcgctg gcgctcgttg aggctgattc actggcactc
2040gttgaggccg attcgctggc gctcgttgat gcagattcgc tggcactagt agaagctgat
2100tcactggcgc tcgttgatgc cgattcactt gcacttgtcg atgcggactc acttgcactc
2160gttgatgcac tttcgcttgc acttgtggat gcggattcgc tggcactcgt tgatgcactt
2220tcgctagcac ttgtcgatgc cgattcactt gcactcgttg atgcactttc gctagcactc
2280gttgatgcac tttcacttgc acttgtggat gcggattcgc tggcacttgt tgatgcggac
2340tcacttgcac ttgttgaagc cgattcactg gcgctcgttg atgccgattc acttgcactt
2400gtcgatgccg attcactggc gcttgttgat gcggactcac ttgcactcgt tgatgcactt
2460tcacttgcac ttgtggatgc ggattcgctg gcactagtag aagctgactc acttgcactt
2520gtcgatgccg attcactggc actcgttgaa gcactttcac ttgcgcttgt tgatgcggac
2580tcacttgcac tcgttgaagc cgattcgcta gcacttgtcg aagctgattc actggcgctc
2640gttgatgctg attcactggc gcttgttgaa gccgactcac ttgcgctcgt tgatgcactt
2700tcacttgcgc tcgttgatgc cgattcacta gcactagtag aagctgattc actggcgctt
2760gttgatgcag attcgctggc acttgtcgat gccgattcgc tagcactagt agaagctgat
2820tcactggcgc ttgttgatgc agattcgctg gcacttgtcg atgccgattc gctagcacta
2880gtagaagctg attcacttgc acttgtcgat gccgattcac tggcgctcgt tgatgccgat
2940tcgctggcac tagtagaagc tgactcactt gcacttgtcg atgccgattc actggcactc
3000gttgatgcac tttcgctagc acttgtagat gcggattcac ttgcactcgt tgatgcactt
3060tcactggcac tcgttgatgc actttcgcta gcactcgttg aagcactttc acttgcgctt
3120gttgatgcgg attcgctggc actcgttgat gcactttcac ttgcgctcgt tgatgccgat
3180tcacttgcgc ttgtggatgc ggactcactt gcactcgttg atgcactttc gcttgcactt
3240gtggatgcgg attcgctggc actagtagaa gcagattcac ttgcgctcgt tgatgccgat
3300tcacttgcgc ttgtggatgc ggactcactt gcactcgttg atgcactttc acttgcactt
3360gtggatgcgg attcgctggc actagtagaa gctgactcac ttgcactcgt tgaagcactt
3420tcacttgcgc ttgtggatgc ggactcactt gcacttgtcg atgctgattc gctagcacta
3480gtagaagctg attcacttgc actcgttgat gcactttcac ttgcgcttgt tgaagccgac
3540tcacttgcgc tcgttgatgc cgattcactt gcactcgttg aggcactttc acttgcgctt
3600gttgaagccg actcacttgc gctcgttgat gcactttcgc tggcacttgt cgatgccgat
3660tcgctggcac tagtagatgc ggactcactt gcgctcgttg aagccgattg gcttgcacta
3720gtagaagctg attcactggc gctcgttgag gctgattcac tggtactcgt tgatgcactt
3780tcgctagcac tcgttgaagc actttcactt gcgcttgtgg atgcggactc acttgcacta
3840gtagaagcag attcacttgc gctcgttgat gccgattcac ttgcacttgt cgatgccgat
3900tcacttgcgc ttgtggatgc ggactcactt gcactcgttg atgcactttc gcttgcactt
3960gtggatgcgg attcgctggc actagtagaa gcagattcac tggcgctcgt tgatgccgat
4020tcacttgcac ttgtcgatgc cgattcactt gcactcgttg atgcactttc actggcactc
4080gttgatgcac tttcgctagc actcgttgaa gcactttcac ttgcgcttgt tgatgcggac
4140tcacttgcac ttgttgaagc cgattcactg gcgctcgttg atgcactttc acttgtgctt
4200gttgaagccg actcacttgc gctcgttgat gcactttcac ttgcgctcgt tgatgccgat
4260tcactagcac tagtagaagc tgattcactg gcgcttgttg atgccgattc gctggcactt
4320gtcgatgccg attcgctagc actagtagaa gctgattcac tggcacttgt cgatgccgat
4380tcactggcgc tcgttgatgc cgattcgctg gcactagtag aagctgactc acttgcactt
4440gtcgatgccg attcactggc actcgttgat gcactttcgc tagcactcgt tgatgcactt
4500tcgctagcac tcgttgatgc actttcactt gcgctcgttg atgcagattc gctagcacta
4560gtagaagctg actcacttgc acttgtcgat gccgattcac tggcactcgt tgatgcactt
4620tcgctagcac tcgttgatgc actttcactt gcgcttgttg aagccgactc acttgcgctc
4680gttgatgcag attcgctagc actagtagaa gcagattcac ttgcgctcgt tgatgccgat
4740tcacttgcgc ttgtggatgc ggactcactt gcactcgttg atgcactttc acttgcactt
4800gtggatgcgg attcgctggc actagtagaa gctgactcac ttgcactcgt tgaagcactt
4860tcacttgcgc ttgtggatgc ggactcactt gcacttgtcg atgctgattc gctagcacta
4920gtagaagctg attcacttgc actcgttgat gcactttcac ttgcgcttgt tgaagccgac
4980tcacttgcgc tcgttgatgc cgattcactt gcactcgttg aggcactttc acttgcgctt
5040gttgaagccg actcacttgc gctcgttgat gcactttcgc tggcacttgt cgatgccgat
5100tcgctggcac tagtagatgc ggactcactt gcgctcgttg aagccgattg gcttgcacta
5160gtagaagctg attcactggc gctcgttgag gctgattcac tggtactcgt tgatgcactt
5220tcgctagcac tcgttgaagc actttcactt gcgcttgtgg atgcggactc acttgcacta
5280gtagaagcag attcacttgc gctcgttgat gccgattcac ttgcacttgt cgatgccgat
5340tcacttgcgc ttgtggatgc ggactcactt gcactcgttg atgcactttc gcttgcactt
5400gtggatgcgg attcgctggc actagtagaa gcagattcac ttgcgctcgt tgatgccgat
5460tcacttgcac ttgtcgatgc cgattcactt gcacttgttg aagcagattc acttgcgctc
5520gttgaggccg attcgctggc actcgttgat gccgattcgc tagcactagt agaagctgat
5580tcacttgcgc tcgttgatgc cgattcactt gcacttgtcg atgccgattc actggcgctt
5640gtggatgcgg actcacttgc actcgttgat gcactttcac ttgcacttgt ggatgcggat
5700tcgctggcac ttgtcgatgc cgattcactg gcgcttgttg atgcggactc acttgcactc
5760gttgatgcac tttcacttgc acttgtggat gcggattcgc tggcactagt agaagctgac
5820tcacttgcac ttgttgaagc cgattcactg gcgctcgttg atgcactttc acttgtgctt
5880gttgaagccg actcacttgc gctcgttgat gcactttcac ttgcgctcgt tgatgccgat
5940tcactagcac tagtagaagc tgattcactg gcgcttgttg atgcagattc gctggcactt
6000gtcgatgccg attcgctagc actagtagaa gctgattcac ttgcgctcgt tgatgccgat
6060tcgctagcac ttgtcgaagc tgattcactg gcactcgttg atgcactttc acttgcactc
6120gttgatgccg attcgctagc acttgtcgaa gctgattcac ttgcgctcgt tgatgctgat
6180tcactggcgc ttgttgaagc cgactcactt gcgctcgttg atgcactttc acttgcgctc
6240gttgatgccg attcactagc actagtagaa gctgattcac tggcgcttgt cgatgccgat
6300tcgctagcac ttgtcgaagc tgattcactt gcactcgttg atgctgattc acttgcactt
6360gtcgatgctg attcacttgc gctcgttgat gctgattcgc tggcacttgt cgatgccgat
6420tcacttgcgc ttgttgaagc tgattcactt gcgcttgttg atgcggattc gcttgcactc
6480gttgatgcac tttcacttgc gctcgttgat gccgattcgc tggcgctcgt tgatgcactt
6540tcacttacgc tcgttgatgc actttcactt acgctcgttg atgcactttc acttacgctc
6600gttgatgcac tttcacttac gctcgttgat gcactttcac ttacgctttt tgatgccgat
6660tcgctggcac tcctcgttga agcggattcg ctggcactcc tcgttgaagc ggattcactt
6720acgctcgttg atgcgctagt cgaagtactc gtcgaggtgg attcctgttc actcttactc
6780gtcaattga
678931132DNAArtificial SequenceBased on Lactobacillus reuteri
31atggagatat tggtaacgtt atttgatttg gtgtttttta ttacgtttat agtcgcaatt
60gtctatggta ttaggtggtt taaaggaaga aaagataaag aaaatgaatc tcttaagaaa
120cgccgtttgt aa
13232240DNAArtificial SequenceBased on Lactobacillus reuteri 32atgattaact
taaacttagc aggcttagat tttgtaatga cggcactttt tattgtgttg 60tttacagaac
agttgaaaaa tgcccgaact cagcgtgatg ctctgattgg tttagcattt 120gcaattattt
gtttactatt ttgcaacaag aatgtttttc tattagtgac attagtaaca 180cttgtcgcac
tgttttcatt aaattactta atcacgagga gaaaaaatga cattaactga
24033123DNAArtificial SequenceBased on Lactobacillus reuteri 33atgtcagaga
tgaaaaatcg cgtaattaat tttcggaatg ataacttagc caaacttata 60gtcaattatt
atggaaatag tcaattaagt gtgcatatta ctaataatat gttttttgaa 120tga
12334786DNAArtificial SequenceBased on Lactobacillus reuteri 34atgaaacgca
aaattgcatt agctcaactt gatattcaat taggaaatcc tgccgaaaat 60tatcaaaaag
ctaaacaagc gattgaagaa gctgctagtc accatgcaga tatcgttgtc 120ttgccggaga
tgtggaatgc tggctatgcc ttagatcaat tagcagaatt ggcagatgaa 180aacggtcaaa
agacacaaaa atttcttagt gagttagcgt tagaaaatca aattaacatt 240gtcggtggtt
cagtagcggt gagatgtgga caatcttttt tcaatacaac ctatgtttat 300gatcaaaagg
gaaatctaat tagcagttac gagaaggtgc atttatttgg actaatgaat 360gaagaccgat
atctaaaagc cgggcaaaaa gaaaatcact ttgaattagc tggggttccg 420agtgcaagtt
ttatttgtta tgatttgcga ttccctgaat ggattagaac agtcactcgt 480tatggaactg
atatcttata tttttcggca gaatggccaa gcaaacggat taaacaatgg 540aaaataatgc
ttcagtcacg ggcaattgaa aatcaagcct ttgtagtcgc ggtcaatcgt 600gttgggacgg
atttagagaa tagctttaat ggtcattcgt tagtaataga tccgcttggg 660cagattatcc
atgatgcagg agaagttgaa caagtaagtt atgcagaaat tgacttagcg 720cagttagcac
aggttcgggg gccgattccg gtgtttaagg atcgccgacc aagtctttat 780cattaa
78635504DNAArtificial SequenceBased on Lactobacillus reuteri 35atgcaaaata
aagatgcttg tacatcaatt atggtcggta aaaaggcttc tctcgacggt 60gctaattata
ttgctcgtaa tgaagatcgc gtaaaagcaa ttgaacccaa gcgattttta 120gtaaaaccgg
cagtaaaagg acgccacgaa acctacgtat caccttacaa taaagtaact 180gtagctttgc
cggaagagag aatgcgttat acttctacgc ctacccttga tcaaacagcc 240ggacctaatg
aagaagatgg aattaatgaa gcaaatgtgg cagcttcctt tactgagagt 300gtttatgcaa
atgatcgggt gttagcatat gatccatacg taaaaaatgg cctggcagaa 360gactcacttt
gtactttagt attaccgtat attcattctg cccgtgaagg agttgaatat 420actggaaaat
taattgctga attgggctct gctgagggaa atggaatgca atttgcagat 480gcagatgata
tttggtatat gtaa
504361533DNAArtificial SequenceBased on Lactobacillus reuteri
36atgaattatt ttatcggtgt tgatgttgga actacttcta caaaggcagt tctatatgac
60caaaatgcaa ctgtgttaga tcaatttagc caaggttatt ccctttaccg cgatgctagt
120ggaatggctg aacaaaaccc aactgcaatt gtcgaagcag tcgaaaaagt tattcatgat
180gcagcacaaa aagcagattt aacaaatgga aaattgttag cggtatcatt ttctagtgct
240aaccaaagtg tgattatgct cgacaagaat ttcaatcccc tttcacgggt catcacttgg
300gctgataccc gtgcacgtga tgtcgccaac gaattaaaga atagtcctgc tggtcagcaa
360atctatgcta aaacaggtac acctattcat ccaatgtccc cattgaccaa gattatgtgg
420ctcaataaga cacaagcaga taaggttgct caaactgcat attttggcga tatcaaatcc
480tacctcttcc accagttttt caatacattt aaggttgatg tttccatcgc ttcatgtacc
540ggaatgatga atgtcaatac gtgtgactgg gacgatcaag cattggaact cgctaacgtc
600gactgttccc aattaccaga aatcgtgaac ggaacaaccc aagcgattgg cctaacagca
660gcggcgcaag caaaaatggg tatccccgct gacacgccat ttgtctatgg tgcctttgac
720ggtgctttat ctaatttagg tgtgggggca attaagcaaa atactgttgc cattacgatt
780ggaacttcgg ctggtgttcg ggtagtaact gaccatccag tgatcgatcc tcagcaacga
840ctcttctgtt acgccgtgga taaaggttta tgggtcatcg gcggtccgct taataatggt
900ggcgatgtct atcagtgggc cgttgaacac ttagttgacg ctagtgcagt taaaaatgaa
960aatattgatc cctacactct tgctaaccga gttattgaag gtgttcccgc cggagctcac
1020ggtttgctct tccacccatt ccttggcggt gaacgggcac cattatggga cgctaatgcg
1080cgcggtagtt tctttggact ttcccacatt catactcgtg ccgatatgct gcgctcagta
1140atggaaggaa tttgtatgaa tattgcaact gttttccaag cggttcgtga tcttgttggt
1200aatcctgcaa gcgtaactgc aactggcggt tttgcgcgag ctgaagtttg gcggcaaatg
1260ttagcagatg tcttgaactg tccggtcaat atcccgaact catttgaatc tggttgtctc
1320ggtgcaatca ccatggcaat gaagagttta ggaatgattg aaaactatga aatcattaaa
1380acattagttg gtgatatcag ttcttatcag ccaaatcaag atgcggttaa tgtttatcaa
1440aattacttac cactttttaa gcaggtcgaa ggattattaa caccagccta ttcgaccatc
1500gctaaattac aacaacaatc tactactcat tag
153337195DNAArtificial SequenceBased on Lactobacillus reuteri
37atgacaacat caatgatcca cagtagaagt atgttggcga aagtgattgc agaatcacct
60tcacctttta ttataccaat tttttgtcct aatgtaataa agattatctt tttatctata
120aattatttta tgaaaagagt ggaaaaggca agaagagcaa tcaaaaagcc aattttaaca
180attttattaa gttga
19538570DNAArtificial SequenceBased on Lactobacillus reuteri 38atgagcaaac
tattacttga tgaaagaccg ttacaagttc aggcatcgtt agctggagcg 60ttgaaaagct
tagacgaagc tgttattctc cagcagcttc actattggct tcaacgttct 120aatacagtaa
gagacaatca caaatgggtc tataacagca tggctgattg gaataaacag 180ttcccttggc
tttctagaaa ggctctatcg aaccacttta agaaattaga aaaacgagga 240ctaattatta
caggcaacta taataaatta tcttttgaca aaacaaagtg gtatcgaatt 300gactatgacg
cattttccca tttggaacaa cgattgggta gaaactaccc aacgaatggg 360aagaatctac
ccaatggaga cggtaaaaac tgcccaatcg gagaggaaga atctacccaa 420ccaataccaa
tagactacca agagactaca caaaagacta ctacaagaga taaagggcag 480gcacagccag
cccaaccttc cattgctgca cagcggcgag aagttgttga atatctcaat 540caaaaaaact
ggcaagcact tcaagcctga
57039438DNAArtificial SequenceBased on Lactobacillus reuteri 39ttgaataatt
ttcaaaaggc aattttcttg ttgcagaata tcgacaagct taaacagctt 60aatggtaaag
cgatgactct tactgagttc tctaaaataa ctgatgtttc acggccaacg 120ttgtataaat
acattcagca tccagaaaca atgagtagtt cgtttgtaaa taaagcggcc 180atgctctacg
acaaggttgt taaatttcaa gatattcttg atacagttca gcgtgaagat 240aaacaattta
agactaccag gcaggaattg attaagcttt tagagtctaa tgtagctaat 300attgaagtta
cagattatac aaaagcaatc gcgacagtaa ttattagtga cttaaaagaa 360gaaaattcaa
gtctgctaaa agcgttaagt aagcaattac catttaaacc aaatttaaat 420gataatttgt
caaaatag
43840333DNAArtificial SequenceBased on Lactobacillus reuteri 40gtgaagatga
atagtatgac aaacaaccaa aaagaaagtt ggaacgttgg caactataaa 60atcaatgtat
taccagatga tgagttccag caattgttaa agaaccaacg ccaacttcaa 120cagatcattg
aaagtatgcc actaccaacc gaccccaatg ttgatctagt taaaaagatt 180cattcccaac
tccctattac aaactgggct tgggaattaa ctaaacaacg agaacatgag 240gaaaagttaa
agaaacaaaa gcagcgaatt gcacagcaat cgcttaacta tccaacaaac 300ctcaagaaac
cggataatgg cctttcccta taa
33341153DNAArtificial SequenceBased on Lactobacillus reuteri 41atgaattcta
atttgaaaaa gaatttgatt atcgcaaatg gatttctact actaataata 60atattttatg
ttttattaca tatgggtcca ttaaatatga aagtcttatt agtaggattg 120gtattaatga
atctgacagt aatatttaaa taa
153421395DNAArtificial SequenceBased on Lactobacillus reuteri
42atggataaat taacattgaa aaaactaatt attattacat taggcatgct aatggtattt
60cttttaggta tgcaccttca tcaaaagaca cactttaaca aaaacgtgaa gattaataat
120attccagtcg gaggtcttac tgttcaacag gcatataata aagtaagtaa tactaaaaga
180aaatcaaaaa tctacattaa caaaaagtta gtttattcag gtaaaagtac tgactcaggt
240tttaagttat ctgataaaga aagatttagt aaggcgttac attaccaata cacttttttt
300ccctcacgaa aacatgaaaa tttgctagtt gagccagctg atttagataa gtcagcgtta
360aataatattg attcggcaat agtagctagg attcatcagc tcaatatagg cagaaaggcc
420ccacgtgatg catacgccgt ttaccagaat aataaagttt cagttattcc agcaattgat
480gggacacgat atagtgaaca aggactttgt aatattgcta ataaggaatt tgttaatggg
540acaattcatt taactcctaa ggttattact cctttatcgg caaacagtaa agtagttcaa
600gatgaaaaga aacacctgag taaactacaa aatcgatcgg ttgtttatca ggttcagaaa
660acaaaatata attttaaagc gtctaatgtc atttctaaag caacttatca gcatgggaaa
720taccattttg aaactgacaa cgttaaatcc aagattgcca atataaataa taagcaagca
780acattaggaa agagctttaa atttagaact gattctggaa aagttatttc tacatctaat
840cagggaacat atggttggaa aataagtagc aagcaggcag gacaaacact ctctaaagcg
900ttagctaata atgttaagag cgttaatgcc gaaaatgata tttacggtaa aggctatagt
960catcttggta ctggatattc ggctgtgaat aatcatgggc ttggtaatac ttatgtggct
1020gtatcattag ctaaacagca tgcttggttt tataaaaatg gaaaatgtgt actgagtaca
1080gatattgtta gtggatcaga tgacgctaat aataggactc ctaaaggtgt ttggtatatc
1140atgtatcaac aaacgccatc agttttacgt gggactaatg atgatggttc caagtatagt
1200agtcctgttc agtattggtc tccgtttact ttatcagggt gtggctttca tgatgctagt
1260tggaggcata attggtctaa aacagcttat aaacagactc atggtggctc acatggctgt
1320attaacatgc atccggaaaa tgcaggagac ggtttccatg cccttactaa aggagaaccg
1380gtaataattt attag
1395431932DNAArtificial SequenceBased on Lactobacillus reuteri
43atgcaattaa accataaatt aggagttttc ttggcagcgc catttgctct actggtttta
60tcagctacaa acgtgcatgc cgataacatt caaagtaata gtaaccagac aatcagtaat
120atgagtttgc aaactaatga cacaaagact caacaaaatg ttgtaatgtc aaacgatgca
180aaagctcaaa ttactgtaaa tcctagttct aatgctaatt ctagttctgt agcaaagata
240aatgaaaaga ataatgtaaa atcggatact gacaatacta atgtcgaatc aaatgctgat
300aatattggga acattgcttc tagcgattcc acggcagtgg ctaattctgc tagttccgat
360aatattcagt catttaacgt aaatacgcag gaacagcctg caataaatgt atctgaacta
420acaaccgaag agtatgttac gaattacact caacaacaga tcaataatgc gacgactatt
480catgattact ttataaatca aggatggaca ccaaatgcta ttgctggaat gcttggtaac
540tttgtttcag agtcaggttt aatcccagac ttacatcaat atggtggtgg gcctggttat
600gggttagctc aatggccatt taatagtgta gtaaattggt gtcgtaataa tggatatgat
660tatcgtactt tgcaaggaca atgtgcatat attgaatatc aaatgactca tggacagcag
720tattatccat cagcttactc tagaatgacc gctaatgaat atatgcatag ttatgcttca
780gcatatactt taggtatgat ttggcttaat aactttgagc gacctgcaaa taggaatcag
840ccagctcgtg gtcaacaggc tcaatactgg tatcagtatt tccaaagtca tggttctaca
900tcagcaccgg tacaacaaaa tcctagtaca ccagcaacaa ctcctagctc aagtcgaatg
960agtcaacacg ggacattcaa agttgcttat ggattaaatg tacgccaagc accaagtaca
1020tcggcagcta ttgtaacgta ttacaatggt ggtcaaagct ttacatatga ttcaaagatt
1080gaagctaacg ggtatctttg ggtatcatac atgagttata gtggcgtacg tcgttatgtt
1140gcaattaaga atttgaataa tggaacgact tacggttatg attcgaataa cttctcatac
1200agtgctcctg catcttcaac accatctact aatgtgccaa gtacgccagc accaagtaca
1260tctacttcat caactgagaa gcaatatgga acattcaaag ttgcttatgg attaaatgta
1320cgccaagcac caagtacatc ggcagctatt gtaacgtatt acaatggtgg tcaaagcttt
1380acatatgatt caaagattga agctaatggg tatctttggg tatcatacat gagttatagt
1440ggcgtacgtc gttatgttgc gattaagaat ttgagtaatg gaacaactta cggttacgat
1500tcaaataact tttcatttaa tgggactcca gtaacatcaa ataataatcc ttctagtact
1560ccggcagttc cgcaaggtaa taagggccaa caagttgttg ctcttgcacg tcaacaaata
1620ggtaaacctt atgtttgggg agcaaccggt cctaattcgt ttgattgttc aggactcgtg
1680cagtatgttt atcgtcaagt tggtgttaac ttaccacgga ctacaactca acaagaatat
1740tgtggacatg ctgtaagctt taataatctt caacctggag atctaatgtt ctggggaaag
1800tatggtagtg catatcacgt tggaatctat accggaaacg gtaatgtttt atttgcaccg
1860caacctggtc aaacagttaa ggaacaacca atgcgctatt acatgcctgc ctttgcaaga
1920agagtattgt aa
1932
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