Genetically modified lactobacillus and uses thereof

Abstract

The present invention relates to the efficient delivery of anti-infective activity, immune modulators, or growth-promoting biomolecules directly to the gastrointestinal tract of animals via a biodelivery platform.SOLUTION: The biodelivery platform can be a genetically modified microorganism. Delivery can be achieved using Lactobacillus species fix in the gastrointestinal tract. The anti-infective activity can be a bactericidal or bacteriostatic peptide, an antibody or fragment thereof that specifically recognizes a pathogen, or a phage or lytic peptide derived from a phage that specifically targets a particular pathogen.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 801,307, filed February 5, 2019, which is incorporated herein by reference in its entirety.

[0002] FIELD OF THE INVENTION The present invention relates to live delivery platforms, such as genetically modified bacteria, that deliver prophylactic or therapeutic anti-infective activities, immunomodulators, or growth-promoting biomolecules directly to the mucosa of animals in need thereof. [Background technology]

[0003] Direct fed microbials (DFM), often referred to as probiotics, are microorganisms that colonize the gastrointestinal tract of an animal and provide some beneficial effect to the animal. The microorganisms can be bacterial species, such as Bacillus, Lactobacillus, Lactococcus, and Enterococcus. The microorganisms can also be yeasts or molds. The microorganisms can be fed to the animal orally or mucosally, or in the case of birds, fed to the fertilized egg, i.e., in ovo.

[0004] The beneficial activity provided by the DFM may be the synthesis of vitamins or other nutrient molecules required for the healthy metabolism of the host animal. The DFM may also protect the host animal from diseases, disorders, or clinical symptoms caused by other pathogenic microorganisms. For example, the DFM may naturally produce a factor that has inhibitory or cytotoxic activity against a specific species of pathogen, such as harmful or disease-causing bacteria. However, the DFM may not be able to produce such a factor in sufficient amounts to reduce infection of the host by the pathogen, or the factor may only affect a limited set of pathogens, leaving the host vulnerable to other pathogens.

[0005] More potent or broader spectrum antibiotics can be administered to the host animal, for example, orally or parenterally, but these may have a limited duration in the host and therefore require repeated administration. Oral delivery may result in degradation of the antibiotic or may not deliver the antibiotic to the specific anatomical site where the therapeutic effect is most needed. The development of antibiotic resistance by pathogens is another significant concern. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] EP0700998 [Patent Document 2] W02012 / 019054 [Non-patent literature]

[0007] [Non-Patent Document 1] VA Fischetti, Viruses, vol. 10, no. 310 (2018) [Non-patent document 2] R. Vazquez et al., Frontiers in Immunology, vol. 9, article 2252 (2018) [Non-patent document 3] de Man, JD; Rogosa, M.; and Sharpe, ME "A Medium for the Cultivation of Lactobacilli", J Appl Bact. 23: pp. 130-135 (1960) [Non-patent document 4] Sakaguchi et al., Bioscience of Microbiota, Food and Health, 32:59-68 (2013) Summary of the Invention [Problem to be solved by the invention]

[0008] What is needed is a delivery system that can continuously deliver anti-infective molecules directly to the gastrointestinal or respiratory tract, where pathogenic bacteria proliferate within a host. The gastrointestinal and respiratory systems are also frequent sites of pathogen entry into the host. Preferably, the delivery system is a live, genetically modified microorganism, such as a bacterium, that can colonize the host's gastrointestinal or respiratory tract and directly deliver antibiotic factors to reduce the number of pathogens or block their entry. For example, in ovo delivery of a biodelivery platform could prevent early pathogen colonization of embryos, possibly by competitive exclusion or direct or indirect anti-infective effects. In ovo delivery has the additional advantage of avoiding any colonization limitations of genetically modified microorganisms due to maternal antibody interference. Preferably, the live bacterial delivery system synthesizes the anti-infective factors in sufficient quantities to have the desired effect against the pathogen. The targeted pathogen may be, but is not limited to, bacteria of the genera Salmonella, Clostridium, Campylobacter, Fusobacterium, Staphylococcus, or Streptococcus, or E. coli, or a parasite such as an Eimeria species. Preferably, the live bacterial system persists in the host's gastrointestinal tract for a period of time. Preferably, the live bacterial delivery system produces a broad spectrum of anti-infective factors or multiple anti-infective factors so that a variety of pathogens are targeted. Alternatively, a combination of bio-delivery systems could be administered to a single animal with genetically modified bacteria producing multiple anti-infective factors, immunomodulatory molecules, or growth-promoting biomolecules, or any combination thereof. Thus, more than one disease state may be prevented or reduced, or diseases and syndromes with multiple causes may be effectively treated.

[0009] The present specification provides the disclosure of anti-infective peptides, including novel mersacidin-like peptides that target multiple bacterial species. Antibodies, including single-chain antibodies, that target specific pathogens and pathogenic molecules are also disclosed. Phages or phage lytic peptides that target pathogenic species are also disclosed. A lactobacillus expression system is also provided that can produce high levels of at least one or many of the above molecules, preferably as surface-displayed or secreted molecules. [Means for solving the problem]

[0010] The present invention provides a biodelivery platform comprising a genetically modified microorganism. The genetically modified microorganism comprises an expression cassette including one or more of a promoter for transcriptional expression, a nucleic acid sequence encoding a signal sequence for secretion, a nucleic acid sequence encoding a cell wall anchor, at least one heterologous coding region encoding a desired biomolecule, a nucleic acid sequence encoding an expression peptide tag for detection, and a terminator for translation and transcription termination. The genetically modified microorganism may be a bacterium, yeast, or fungus. The genetically modified bacterium is preferably a Bacillus, Lactobacillus, Lactococcus, or Enterococcus. The genetically modified bacterium may also preferably be Escherichia coli. The genetically modified bacterium may also preferably be a Lactobacillus reuteri strain.

[0011] The present invention provides an expression cassette in a genetically modified microorganism that may include a promoter for transcriptional expression, which may include the nucleic acid sequences of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:41, SEQ ID NO:42, and SEQ ID NO:43.

[0012] The present invention provides an expression cassette in a genetically modified microorganism that can include a nucleic acid sequence encoding a signal sequence for secretion, which can be at least 20 amino acids, at least 25 amino acids, at least 30 amino acids, at least 35 amino acids, at least 40 amino acids, at least 44 amino acids, at least 50 amino acids, at least 55 amino acids, at least 60 amino acids, or at least 65 amino acids. The signal sequence for secretion may also be 20 to 65 amino acids, 20 to 60 amino acids, 20 to 55 amino acids, 20 to 50 amino acids, 20 to 45 amino acids, 20 to 40 amino acids, 20 to 35 amino acids, 20 to 30 amino acids, 25 to 65 amino acids, 25 to 60 amino acids, 25 to 55 amino acids, 25 to 50 amino acids, 25 to 45 amino acids, 25 to 40 amino acids, 25 to 35 amino acids, 25 to 30 amino acids, 30 to 65 amino acids, 30 to 60 amino acids, 30 to 55 amino acids, 30 to 50 amino acids, 30 to 45 amino acids, 30 to 40 amino acids, or 30 to 35 amino acids. The signal sequence for secretion may comprise an amino acid sequence that is a fragment of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:40, wherein the fragment has a length as indicated herein. The signal sequence for secretion may comprise an amino acid sequence that is an amino-terminal fragment of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:40, wherein the fragment has a length as indicated herein.

[0013] The present invention provides an expression cassette for use in a genetically modified microorganism, which may include a nucleic acid sequence encoding a cell wall anchor peptide. The cell wall anchor peptide may have a length of 100 to 250 amino acids, 100 to 225 amino acids, 100 to 200 amino acids, 100 to 175 amino acids, 100 to 150 amino acids, 125 to 250 amino acids, 125 to 225 amino acids, 125 to 200 amino acids, 125 to 175 amino acids, or 125 to 150 amino acids. The cell wall anchor may include an amino acid sequence that is a fragment of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, or SEQ ID NO:40, wherein the fragment has a length as indicated herein. The cell wall anchor may include an amino acid sequence that is a carboxy-terminal fragment of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, or SEQ ID NO:40, wherein the fragment has a length as indicated herein.

[0014] The present invention provides an expression cassette in a genetically modified microorganism comprising a heterologous coding region encoding a desired biomolecule. The desired biomolecule may be a biomolecule with anti-infective activity, a probiotic factor, an immunomodulator, or a growth-promoting biomolecule. The biomolecule may have anti-infective activity active against pathogenic bacteria or parasites. The parasite may preferably be an Eimeria species. The pathogenic bacteria may preferably be Salmonella, Clostridium, Campylobacter, Staphylococcus, Streptococcus, Fusobacterium, and Escherichia coli.

[0015] The present invention provides an expression cassette in a genetically modified microorganism containing a heterologous coding region encoding a desired biomolecule with anti-infective activity. The anti-infective biomolecule may be a bactericidal peptide, enzyme, lysin, phage, or antibody. The bactericidal peptide may be a mersacidin-like molecule. The mersacidin-like molecule may comprise the sequence disclosed herein as SEQ ID NO:2 or SEQ ID NO:4. The desired biomolecule may be an enzyme. The enzyme may comprise the sequence disclosed herein as SEQ ID NO:5 or SEQ ID NO:6. The desired biomolecule may be a lysin. The lysin may comprise the sequence disclosed herein as SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, or SEQ ID NO:28. The desired biomolecule may be a phage or a phage in prophage form. The phage genetic material may comprise the sequence disclosed herein as SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13. The desired biomolecule may be derived from a Bacillus species. The desired biomolecule may be a Bacillus bacteriocin. The Bacillus anti-infective molecule may comprise the sequence disclosed herein as SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, or SEQ ID NO:48.

[0016] The present invention provides an expression cassette in a genetically modified microorganism containing a heterologous coding region encoding a desired biomolecule, which is an antibody. The antibody may be a single-chain antibody. The single-chain antibody may be derived from a camelid. The single-chain antibody may specifically recognize a molecule produced by a pathogenic microorganism or pathogen. The single-chain antibody may specifically recognize a bacterial protein, such as a toxin or adhesion molecule. The single-chain antibody may specifically recognize a bacterial protein derived from Clostridium perfringens. The bacterial protein may be a protein produced by C. perfringens. The bacterial protein may be C. perfringens alpha toxin or C. perfringens NetB toxin.

[0017] The present invention provides an expression cassette in a genetically modified microorganism that contains a heterologous coding region encoding a desired biomolecule that is an antibody that recognizes C. perfringens alpha toxin or C. perfringens NetB toxin. The single chain antibody may comprise the amino acid sequence as disclosed herein as SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:33, or SEQ ID NO:34.

[0018] The present invention provides an expression cassette in a genetically modified microorganism that includes a heterologous coding region encoding a desired biomolecule that is a probiotic factor. The probiotic factor may be an agglutinin receptor. The agglutinin receptor may comprise the sequence disclosed herein as SEQ ID NO:9 or SEQ ID NO:10.

[0019] The present invention provides a genetically modified microorganism comprising an expression cassette. The expression cassette may include a promoter for transcriptional expression and at least one heterologous coding region encoding a desired biomolecule. The expression cassette may also optionally include one or more of a nucleic acid sequence encoding a signal sequence for secretion, a nucleic acid sequence encoding a cell wall anchor, a nucleic acid sequence encoding an expressed peptide tag for detection, and a terminator for translation and transcription termination. The expression cassette may include a promoter having a sequence disclosed herein as SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 41, SEQ ID NO: 42, or SEQ ID NO: 43. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule such as a bactericidal peptide, an enzyme, a lysin, a phage, or an antibody. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule with anti-infective activity. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule having a sequence disclosed herein as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0020] The present invention provides a genetically modified microorganism comprising an expression cassette, wherein the genetically modified bacterium is a Bacillus, Lactobacillus, Lactococcus, or Enterococcus. The genetically modified bacterium may be a Lactobacillus reuteri strain.

[0021] The present invention provides a genetically modified microorganism comprising an expression cassette, wherein the expression cassette is located on a plasmid. The plasmid may comprise the sequence disclosed herein as SEQ ID NO: 8. The present invention provides a genetically modified microorganism comprising an expression cassette, wherein the expression cassette is located on a bacterial chromosome. The expression cassette located on the bacterial chromosome may be inserted into a transposase locus. The expression cassette located on the bacterial chromosome may be inserted into a uracil phosphoribosyl (UPP) transferase locus. The expression cassette located on the bacterial chromosome may be inserted into a pyrE locus.

[0022] The present invention provides a method for reducing pathogenic bacterial colonization in an animal. The method may include treating an animal in need thereof with a biodelivery platform. The biodelivery platform includes a genetically modified microorganism. The genetically modified microorganism includes an expression cassette containing one or more of: a promoter for transcriptional expression, a nucleic acid sequence encoding a signal sequence for secretion, a nucleic acid sequence encoding a cell wall anchor, at least one heterologous coding region encoding a desired biomolecule, a nucleic acid sequence encoding an expression peptide tag for detection, and a terminator for translation and transcription termination. The genetically modified microorganism may be a bacterium, yeast, or fungus. The genetically modified bacterium is preferably a Bacillus, Lactobacillus, Lactococcus, or Enterococcus. The genetically modified bacterium may also preferably be Escherichia coli. The genetically modified bacterium may also preferably be a Lactobacillus reuteri strain.

[0023] The present invention provides a method for reducing pathogenic bacterial colonization in an animal, comprising treating an animal in need thereof with a genetically modified microorganism. The genetically modified microorganism is modified to contain an expression cassette. The expression cassette may include a promoter for transcriptional expression having a sequence disclosed herein as SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:41, SEQ ID NO:42, or SEQ ID NO:43. The expression cassette may further include a signal sequence for secretion having an amino acid sequence that is a fragment of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:40, wherein the fragment has a length as indicated herein. The signal sequence for secretion may include an amino acid sequence that is an amino-terminal fragment of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:40, wherein the fragment has a length as indicated herein. The expression cassette preferably also includes a heterologous coding region encoding a desired biomolecule. The desired biomolecule may be a biomolecule with anti-infective activity, a probiotic factor, an immunomodulator, or a growth-promoting biomolecule. The biomolecule may have anti-infective activity active against pathogenic bacteria or parasites. The parasite may preferably be an Eimeria species. The pathogenic bacteria may preferably be Salmonella, Clostridium, Campylobacter, Staphylococcus, Streptococcus, Fusobacterium, and Escherichia coli. The anti-infective biomolecule may be a bactericidal peptide, an enzyme, a lysin, a phage, or an antibody. The expression cassette may optionally include a nucleic acid sequence encoding a cell wall anchor, a nucleic acid sequence encoding an expressed peptide tag for detection, and / or a terminator for translation and transcription termination.

[0024] The present invention provides a method for reducing pathogenic bacterial colonization in an animal, comprising treating the animal in need thereof with a genetically modified microorganism. The animal may be an avian, human, or non-human mammal. The treatment may be administered orally, parenterally, intranasally, or mucosally. If the animal is an avian, the treatment may be administered in ovo.

[0025] The present invention provides for the use of any genetically modified microorganism disclosed herein in therapy. The present invention provides for the use of bacteria genetically modified to contain any expression cassette disclosed herein in therapy. The therapy may be to reduce colonization of an animal with pathogenic bacteria.

[0026] The present invention provides for the use of any of the expression cassettes disclosed herein in therapy. The present invention provides for the use of any of the expression cassettes disclosed herein in therapy. The therapy may be reducing the colonization of an animal with pathogenic bacteria. The expression cassette should include at least one heterologous coding region encoding a desired biomolecule. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule such as a bactericidal peptide, enzyme, lysin, phage, or antibody. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule with anti-infective activity. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule having a sequence disclosed herein as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0027] The present invention provides the use of any genetically modified microorganism disclosed herein in the manufacture of a medicament for reducing pathogenic bacterial colonization in an animal.The present invention provides the use of a bacterium genetically modified to contain any expression cassette disclosed herein in the manufacture of a medicament for reducing pathogenic bacterial colonization in an animal.

[0028] The present invention provides use of any of the expression cassettes disclosed herein in the manufacture of a medicament for reducing pathogenic bacterial colonization in an animal. The present invention provides use of any of the expression cassettes disclosed herein in the manufacture of a medicament. The medicament may be for reducing pathogenic bacterial colonization in an animal. The expression cassette should include at least one heterologous coding region encoding a desired biomolecule. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule such as a bactericidal peptide, enzyme, lysin, phage, or antibody. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule with anti-infective activity. The at least one heterologous coding region encoding a desired biomolecule may encode a biomolecule having a sequence disclosed herein as SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, or SEQ ID NO:50.

[0029] The present invention provides an antibody comprising the amino acid sequence of SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:50, or SEQ ID NO:34. The antibody preferably binds to a toxin produced by Clostridium perfringens. The antibody preferably binds to C. perfringens alpha toxin or C. perfringens NetB toxin. The present invention provides the use of an antibody comprising the amino acid sequence of SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:50, or SEQ ID NO:34 in therapy. The present invention provides the use of an antibody comprising the amino acid sequence of SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:50, or SEQ ID NO:34 in reducing C. perfringens colonization in an animal. The present invention provides the use of an antibody comprising the amino acid sequence of SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:50, or SEQ ID NO:34 in the manufacture of a medicament for reducing C. perfringens colonization in an animal. The present invention provides a method for treating an animal against C. perfringens infection or colonization, comprising administering to an animal in need thereof an antibody comprising the amino acid sequence of SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:50 or SEQ ID NO:34. [Brief explanation of the drawings]

[0030] [Figure 1] 1 is a table showing antibiotic resistance or susceptibility of Lactobacillus reuteri strains as measured by AVIPRO® Plate. [Figure 2] FIG. 1 shows that pathogenic bacteria, but not non-pathogenic Lactobacillus acidophilus, are killed by L. reuteri strain 3632, as indicated by the apparent "halo" around strain 3632. [Figure 3A] Figure 1 shows chromosomal integration of expression cassettes. Non-limiting examples of suicide vector maps with representative expression cassettes. [Figure 3B] Figure 1 shows chromosomal integration of the expression cassette. Map of potential chromosomal integration sites. DETAILED DESCRIPTION OF THE INVENTION

[0031] As used herein, "genetically modified microorganism" means any microorganism that has been altered from its original state using molecular biological techniques. The genetic modification could be the removal of a portion of the bacterial chromosome or a naturally occurring plasmid. The genetic modification could also be the introduction of an artificial or foreign nucleic acid into a portion of the chromosome. The introduction may or may not interfere with, or disrupt, the expression of a bacterial gene. The genetic modification could also be the introduction of an artificial plasmid. The genetically modified microorganism may be a bacterium, a virus, a yeast, a mold, or a single-cell organism.

[0032] An "artificial nucleic acid" or "artificial plasmid" is any nucleic acid or plasmid that does not occur in nature, but rather is constructed using molecular biological techniques. Although parts of the nucleic acid or plasmid may occur in nature, the parts are in an artificial relationship or configuration.

[0033] As used herein, an "expression cassette" is an artificial nucleic acid constructed to direct the expression of a desired biomolecule by a genetically modified microorganism. The expression cassette includes one or more of the following: a promoter for transcriptional expression, a nucleic acid sequence encoding a signal sequence for secretion, a nucleic acid sequence encoding a cell wall anchor, at least one heterologous coding region encoding the desired biomolecule, a nucleic acid sequence encoding an expressed peptide tag for detection, and a terminator for translation and transcription termination. The promoter directs the initiation of transcription of the coding region into messenger RNA and the translation of the mRNA into a peptide. The signal sequence for secretion, or secretory signal sequence, directs the peptide to be located on the outside of the cell membrane. The extracellular peptide may be a soluble, secreted protein, but may also be cell-associated, particularly if the expression cassette contains a cell wall anchor sequence that attaches the extracellular peptide to the bacterial cell wall. The expressed peptide tag is any amino acid sequence that can be recognized by an antibody or other binding protein. The expressed peptide tag may also bind to inorganic substances, such as a hexa-histidine tag that binds nickel molecules. A terminator for translation may be a stop codon or a spacer open reading frame including a stop codon.

[0034] As used herein, a "heterologous coding region" is a nucleic acid sequence comprising an open reading frame encoding a peptide. The coding region is heterologous to the associated promoter, meaning that the coding region and promoter are not associated in nature.

[0035] As used herein, a "protein" is a sequence of amino acids that assumes a three-dimensional structure. A "peptide" can be used synonymously with protein, but can also be a short linear sequence of amino acids that does not have a defined three-dimensional structure.

[0036] As used herein, a "desired biomolecule" is any peptide that may be beneficial to a host when administered by a biodelivery platform. The desired biomolecule may be a peptide with anti-infective activity, a probiotic factor, an immunomodulatory factor, an anti-antinutritional factor, or a growth-promoting biomolecule. The desired biomolecule may also be a substance with anti-infective activity or a probiotic factor, e.g., an enzyme that produces a vitamin.

[0037] As used herein, "anti-infective activity" includes any activity that prevents infection of a host by a pathogenic microorganism. The following molecules are examples of biomolecules with anti-infective activity: antimicrobial peptides; lysins or lytic enzymes; prophage, phage, or viruses; enzymes, such as those that cleave or disable proteins produced by pathogens; and antibodies that block, inhibit, or eliminate pathogenic molecules. Anti-infectives may also have bacteriostatic activity, slowing, reducing, or preventing the growth of pathogenic species. Non-limiting examples of antimicrobial peptides are members of the mersacidin family or mersacidin-like molecules, such as those described in EP 0 700 998. Non-limiting examples of lysins are lytic molecules produced by phages. Lysins may have specificity for particular pathogenic species of bacteria and have been proposed for use in place of traditional antibiotics. V.A. Fischetti, Viruses, vol. 10, no. 310 (2018); and R. Vazquez et al., Frontiers in Immunology, vol. 9, article 2252 (2018).

[0038] As used herein, a "probiotic factor" is a substance that, when produced by a genetically modified microorganism, is beneficial to the host. A probiotic factor may be an adhesion or agglutinizing molecule that promotes colonization of the host by the genetically modified microorganism and / or extends the period of time that the genetically modified microorganism colonizes the host. The longer the genetically modified microorganism persists in the host, the longer the beneficial effect will be exerted.

[0039] As used herein, an "immunomodulator" may be a cytokine, lymphokine, chemokine, interleukin, interferon, colony-stimulating factor, or growth factor. An immunomodulator may result in a non-specific enhancement of the immune response, or the immunomodulator may increase the number or tissue distribution of immune cells present in the host. An immunomodulator may also reduce an inappropriate immune response, such as, but not limited to, an autoimmune response.

[0040] As used herein, a "growth-promoting biomolecule" could be a growth factor, a transfer factor (such as an iron chelating molecule), a hormone, or any other factor that promotes healthy metabolic activity.

[0041] As used herein, "antinutritional factors" would include protease inhibitors, for example, trypsin inhibitors.

[0042] As used herein, "delivery" or "administration" refers to the act of producing a beneficial activity in a host. Delivery may be direct or indirect. Administration may be by oral, nasal, or mucosal routes. For example, but not limited to, oral administration may be via drinking water, nasal administration may be via spray or vapor, and mucosal administration may be via direct contact with mucosal tissue. Mucosal tissues are membranes rich in mucous glands, such as those lining the nose, mouth, esophagus, trachea, lungs, stomach, digestive tract, intestines, and anus. In birds, administration may be in ovo, i.e., into a fertilized egg. In ovo administration may be via a liquid sprayed onto the eggshell surface or injected through the shell.

[0043] As used herein, the terms "treating," "treat," or "treatment" include suppressing, slowing, arresting, reducing, ameliorating, or reversing the progression or severity of an existing symptom, disorder, condition, or disease. Treatment may also be used prophylactically to prevent or reduce the incidence, occurrence, risk, or severity of a clinical symptom, disorder, condition, or disease. As used herein, the term "reducing" can apply to both prophylactic (e.g., preventative) or therapeutic treatment.

[0044] The following experimental example is an illustrative bio-delivery system comprising the Lactobacillus expression cassette that can be delivered by the bio-delivery platform of the present disclosure.Of course, other embodiments and uses are obvious to those skilled in the art, and the present invention is not limited to these specific illustrative examples or preferred embodiments.The explanatory headings of these examples are merely for convenience and should not affect the interpretation of any results presented therein. [Example]

[0045] L. reuteri strain identification. Seven Lactobacillus reuteri (L. reuteri) strains were isolated from cecal contents of aged birds received from the Poultry Clinic of the University of Hannover at the Research Center, Hannover. All seven strains were confirmed to be L. reuteri by 16S rRNA sequencing.

[0046] Although limited growth was observed for most strains in MRS broth and agar under aerobic conditions (de Man, JD; Rogosa, M.; and Sharpe, ME "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°C. Growth is mostly limited when bacterial strains are cultured on blood agar under anaerobic conditions. None of the strains are 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°C.

[0047] Antimicrobial susceptibility of bacterial isolates was tested using the AVIPRO® PLATE (Figure 1). All strains were resistant to colistin, doxycycline, enrofloxacin, erythromycin, neomycin, oxacillin, penicillin G, trimethoprim-sulfamethoxazole, tetracycline, tilmicosin, and tylosin. All strains except strain 3632 were resistant to streptomycin, and all strains except strain 2098 were resistant to tiamulin. Additionally, resistance to cefpodoxime proxetil was observed in strains 2091, 2095, 2097, and 3630; resistance to cefotaxime was observed in strains 2091, 2095, and 2097; and resistance to lincomycin was observed in strains 3630 and 3632. No strains were found to be resistant to amoxicillin, ceftiofur, erythromycin D, lincomycin / spectinomycin, or rifampicin at the concentrations tested. [Example]

[0048] Selection and anti-infective activity of L. reuteri strains. To select the best strains for further manipulation, L. reuteri isolates are tested for a variety of desirable probiotic and anti-infective properties, such as growth rate, ability to produce hydrogen peroxide, autoagglutination, enzyme profile, survival in the presence of bovine bile and pancreatic enzymes, and sensitivity to heat shock and pH changes. L. reuteri strains are also tested for safety using hemolysis assays.

[0049] In general, all strains behaved very similarly with respect to probiotic properties, including growth rate and ability to produce hydrogen peroxide, except for strain 3632, which exhibits some unique properties, including the ability to autoagglutinate in liquid medium (similar to that of the well-characterized human probiotic strain L. reuteri ATCC 23272). None of the strains were found to be hemolytic on blood agar plates, suggesting that these isolates are unlikely to be pathogenic to humans.

[0050] Whole genome sequencing was performed on L. reuteri strains 2091 and 3632, and the independently isolated L. reuteri strain 170331 of European origin, using PACBIO® sequencing (Amplicon Express). Table 1 provides a summary of the sequencing, assembly, and annotation statistics. Genome structure and organization differ among the strains tested.

[0051] [Table 1]

[0052] Based on genome sequencing data, strain 3632 encodes two bacteriocins belonging to the mersacidin family based on homology to the mersacidin conserved domain. These bacteriocins appear to be unique to strain 3632. The cDNA encoding one mersacidin (mersacidin-El) may be: 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 (SEQ ID NO: 1). This novel open reading frame will encode the following mersacidin-El polypeptide: MDKEELEKIVGNNFEEMSLQKMTEIQGMGEYQVDSTPAASAISRATIQVSRASSGKCLSWGSGAAFSAYFTHKRWC (SEQ ID NO: 2).

[0053] Another cDNA encoding the second form of mersacidin (mersacidin-E2) would be: 1 atggaagaaa aagaattaga aggtgtaata gggaattcgt ttgaaagtat gactgtagag 61 gaaatgacaa aaattcaagg tatgggtgaa tatcaagtag attcgacgcc tggatatttt 121 atggaaagtg ctgccttttc agctcttaca gccaatataa caagacatgc tatgcatcat 181 cattaa (SEQ ID NO: 3). This novel open reading frame will encode the following mersacidin-E2 polypeptide: MEEKELEGVIGNSFESMTVEEMTKIQGMGEYQVDSTPGYFMESAAFSALTANITRHAMHHH (SEQ ID NO: 4).

[0054] L. reuteri strain 3632 encodes another polypeptide that contributes to the anti-infective activity of this strain: capreomycin synthase, involved in capreomycin synthesis, has been confirmed to be expressed in both the culture supernatant and pelleted cells. MVEIAHFGVEAWLNKWEKSATYDISQSTIASLSMHDLLNLDGNNGEEFYEMLDKQQMNYGWIEGSPEFKEEVAKLYHHVDPENILQTNGATGANILALYALINPGDHVIAEYPSYQQLYDIPKSLGADVDYWHIHEEDNWYPRIDDLKAMVKPNTKMICLNNANNPTGTVLDKEFLEQVVEIAKSVDAYVLVDEVYLPLDHPEKFAQIIDLYDKGISTNSLSKTYSVPGVRIGWTATNAEVADIFRKFRDYTMICGGVFNDQLATYVLRHRDQVLARNRKLVLGNLAIYKDWIDHEDRASVIMPQAVSTSFPKLDVPVDIHTFCENLLHDEGVLLVPGDAFDTPGHVRLGYCAPEATLKEGLKRLSKYMHQYD (SEQ ID NO: 5).

[0055] The following colicin V-produced proteins are also expressed in pelleted cells of strain 3632: MILTTFIILILMGCFINGHRRGLLTMTLMLGTYIVAWIVARQGAQLIGGWLKSLLPSIGTPATFSESLLANVNSNLFFYNGIAFMIIFTIVSILCHWGIRQLNWIKRIPVVGTVDKIAGGLISFLIGYLIIYVVLLIMQLFPAGWWQMQIANSELARFMINQTPGIAHLVIDTLVQGG (SEQ ID NO: 6). One of skill in the art will recognize that due to redundancy in the genetic code, multiple nucleic acid sequences will encode the above peptide.

[0056] The functionality of these putative bacteriocins is tested by plating pathogenic bacteria with strain 3632. As shown in Figure 2, the pathogenic bacteria Clostridium perfringens, Staphylococcus aureus, Streptococcus suis, Streptococcus uberis, Escherichia coli (APEC), Salmonella typhimurium, Fusobacterium necrophorum, and Campylobacter jejuni are killed by L. reuteri 3632. The nonpathogenic control, Lactobacillus acidophilus, is not killed. DFM strains such as 3632 may be used to control, limit, prevent, or eliminate pathogenic bacterial infections in pigs (Streptococcus suis), poultry (C. perfringens, E. coli, Salmonella typhimurium, and C. jejuni), and cattle (S. aureus, S. uberis, and F. necrophorum). DFM strains such as 3632 may be used to control, limit, prevent, or eliminate foodborne pathogenic bacterial infections in humans. [Example]

[0057] Other genetic elements of L. reuteri strain 3632. To identify any plasmids that may contain antimicrobial resistance genes, naturally occurring plasmids were isolated and identified by high-throughput sequencing (ACGT). Strain 3632 contains three naturally occurring plasmids, none of which carry any known antimicrobial resistance genes. However, one of the plasmids is maintained at high copy number: 1 TTGGCAATCT TTCACCTATC AGCAAAAATC ATTAGTCGAG GAAAAGGGCA ATCAGCAATT 61 GCCTCGGCTG CTTATCGTTC AGGGAACAAA CTTCACGATG AACGATACGA CGAAACACAA 121 GATTACACA ACAAACGTTT CATCGAACAC TCAAAATCC AACTTCCAGA GAATGCCCCA 181 GCTAAGTATC AAGATAGGGC AACCCTTTGG AACAGCGTAG AAAAGGCAGA AAAAGCTAAG 241 AATTCGCAGT TAGCTAGAGA AATTGAAATA GCCTTACCAC GAGAGCTAAC ACCAACAA 301 CGAGTTAAT TAGTCCACGA TTACGTTCAG AAAACCTTTG TCGATAAGGG AATGGTAGCC 361 GATTGGTCTA TTCACAACCC ACAACCAGAT AAGGATATC CAGAAAAGCC ACAAACCCG 421 CACGCTCATA TCATGCTCAC ACTGCGTAGC TTGCGTTCTA ACGGCTCTTG GGCACCAAAG 481 AAGACAAGTC ACTATGAACT AGAC GAAAAC GGCCAGAAGG TGCCTGTAAT CGATCCTGAG 541 ACAGGCAAAC AGAAGTTAGG GGCGAAAAC CAAAAAATCT GGAAACCAGT ATTACCCCA 601 ACTAATGACT GGAATAACCC CAAAAACGTT GAAAAATGGC GGGCTGAATG GGCGAAGACT 661 TGTAATAAGT ACTTGGCTCC TGACCACCAG ATTGACCACC GCAGTTATAA ACGGCAGGGC 721 AAAAAACAAA TTCCAACAAT CCATGAGGGC TATGTTGCTC GTAAAATGGA AC GAGAAG CC 781 CHANGES CHANGES GGC TTCTTTTAAC CAAATCGTAA AATATTCAA QUESTIONS 841 AAATCGCTTA GAAAGCAAAT TAGGGGCATT ATACGCGAAA TACGGAATCT AGAAAAAAGGA 901 CGTCACCAG REPEAT TCGACTTCAG REPEAT ACCC REPEAT REPEAT 961 AGGAGAGATC AAGCGCTGGG AGGAGGAGTT ACGAGAGATCA TCGGGAGCAA 1021 TCCGGAAACG GTAGAGCCAA CGGAACTGCC GAAGAAGCCC AACGAACAGA TCCTAATCAA 1081 CTTCATCAAC AGTCTTTCGG AGAAACAGCA AGAAGAATTT TCCGAGATTT CCGGCTATTT 1141 GCGGAGCGTC AACGAGAAGC TCGACAGCGA CAACGCCGAC TTAGCCAAGG CTTACAACAT 1201 CATCAAGAAA CAGAAAAACG ACTTGAAGCA GGGCAACAAC AACTTACTCG AACAAAACAT 1261 ACAGCTGACG AACGAAACA ACAGCTTACA ANSWER TTCGAGTTAG AAAAGCTTTT 1321 AGCGACCTTT CTAAGTCCAA AGTCTTGGAA CGATACTACA CTCACTTCCG TCAAACAAAA 1381 ACTCAAGCAA ATCATGCAAAA AGGATTAGAC TACCAAGGAC CAATTCTGGG ACATTCCCGA 1441 GGACGCTCAA GGTAGTTATG CTAGATGAT TAAGCCGTCC GTGGCAACTC CTACGTAAAG 1501 GAGGTGGCAA CATGGCACAT ATACTCCTCT CAGCAGTTTT GAGCCTTCTG GGTTCCTTGA 1561 TAACTGCACT GTTCGCTGAT TGGCTTCGTC GGCGAAAATA GTTTTTGACG GCATGAAGCG 1621 CAAATTAAAA GCCACTCAAC TATTCGCACT AGTTGGGTGG CTTTTTTGCA ACGTGGCAAT 1681 ATACTTCTCT CGGTTAAATT ATAACATGGT TGTTCCAGAA GTGCATTAGG TAGGCGGTTT 1741 GTCCCCCCCC ATGGGTTTTG GCTTCGAAAA TCAATCGTTG AAGTGACCAG CGAAGCTCAG 1801 CTGATGGAGC CCTCATATTC AAGAAGCAGG TCAACGAATG CCAATTCCAA CATGAGGGCC 1861 ATGACTTAGG CCACTGATAC TCGCAAATGA CTGTCACACC AACGGTATTA GCCATTCTGA 1921 TAAGCGAGTC TAACGACTTT TGACGCATAA TCGACCACCT ACCTTATTTT CAAAGCGCCT 1981 CAGAGCTAAT TAGAGTATTC TTCAAGGAGC TTAGCGAGGA TTATAGACGC TTGGCGGACT 2041 TCACTTTCGG CTTGATTGAC CCGTTTAGCG ATCTTGTCAT CATGGCGAGC CACCTTTTCC 2101 AAGTCATGGA GATTATCAGC GATTTGGTCA GTCATGACGG AGTAGTTCTT AATACCCGAC 2161 AGCAGGCTTT CAACGTTAGT ATTCTCAAGG TTTTCGTTGA ATATCATGGT TATTCCTCCT 2221 TATCCTCAAA CTTAGTCATC TTCTGTCTCC TGTTTTAGAG AATTTTCAAT CATGTCTAAT 2281 AATGTTGACA TGTCAATGTT AAATGAATCA AGGCTACCAT ACCGCTTGAT TTGAGTTTTA 2341 ACACTATCCA ATCCATATTC TTCAAGTAAT GCTTTTAATT TACCAGTAAC TTTTTCACCT 2401 AAATGCCCAA AATACTGAAG CCAGCTCTTA AGTAATTCTC GGTACTGGTC AAATTTTTCT 2461 TTTTCAGTAA GCTGTTTCTC AACTTCTTCT TGGTCCTCAG AACCGTTAAC TACTTTCCAG 2521 AGGTCAGGGT CAGTAGTACC CAACTTATAA CCAAGTACCC GATCATATGC TCTGGCCTTT 2581 TCCTTTGGAG TCAAATCAGG ATTAAGGTCA ATATTATCTA GCTTCATACG TTGGTCAGCA 2641 TAACGACCTT TTTCAAAGTC ATCGGCATTC TTGGCTTCAG GTTGCCAAGT GAACTCATAG 2701 CCAACAACAG GACGTCCTCT ACCAGCTCCT CGAATAGTTT TTACGGTTAA GCCACGAATA 2761 ACAGGGGTTA GCTCTTCTTT AATTGGACGT AACACTCTTT TTCTTACGTT ACCCTGGTCT 2821 TTCTTGTAGC TCTTGGGTAG ATCTAGTTGC TTAAATAATT CGTCACTGGT TAACTTCAAC 2881 CGCCCTACTG TTCGATATTG TTTAATTAAC ACTCTTTTTC TTACGTTACC CTGGTCTTTC 2941 TTGTAGCTCT TGGGTAGATC TAGTTGCTTA AATAATTCGT CACTGGTTAA CTTCAACCGC 3001 CCTACTGTTC GATATTGTTT AATCAAGCGA AACATGTTCT TAGCATAAGC AGATTGAAGA 3061 CTATTAAACT GAGCTAGTTG AAATCTTGTC CAATGACTTA AATCATTGAA TAGCTTCTGA 3121 AATAGAGGGT TAACTTGAAC AGTCAGAATC TGTTTACTCC TCTGAATCTG AAATACATTC 3181 CAACAAGCAA ATTGAGTAAT GGTGTCTCCA TCATCGGTGT AGGCATTAAT CTCTAATAGC 3241 TTTTTATTAG TTTTCATCAA ATCTTTTACA AAATTAGATG TACTCCGTTC ATACTTACTA 3301 AGACTTTGTA GTTGCGTAAA TGAAAACTTT AATTTCTGAG TACCCTTTTG ATACGACTGC 3361 TGAACTAGTG TAATAAATAG ATTTAGCTCA TTAGAGTTCA GTCGGCCAAG TGGAATAGTA 3421 TTAAGCCGAT TACTATACTT CACAATTTCA TTACTCAATT TTCTCACCTC AAATATATTTA 3481 TAACATTTTA TCGTACACAA TCAAGAGTAC GTACTTATAG CACACGTACA GTATTAGCGC 3541 GTATATTAAG ACAAAAATTT AGACAAAATG TACCTTATAA CGGACAAAAT GTACCTTATA 3601 AACCGGACAA AATGTACCTT ATAACGGACA AAATGTACCT TATAAAAAAC GAAACTCTTA 3661 CTCTCCCAAG GAGTTTCAAA CCCCTAAAGA GTATTTAAAG AATATATATA AAGATATTTA 3721 AAGAGGCACC ATACGGAAAA TCTCCTTTCT GATTTCAATT TCAGAGAGGA GATTATCACT 3781 AAATTTCAAA ATTCAATTTT TCGCCAAAA CTTTTTTAGT AGTTTTCGGT AACTAGCAAA 3841 ATCAACTTCG TTGATTATTT TGACTATTTC GAAATTCATC AAAAAACTGAA TGCCCGTCTT 3901 TATAGTGAAT TTGTTTAGTG AAGTTCACTA ACTGCTTCAG CATATTCAGT TGACCACGTA 3961 ACCATTGTTC ACTATCAGCA GGACTAATTT GTTCTGATAA TTGCTCTTTT TGGTGGTTAT 4021 AAGCCTTATA AGCCTGATAT TTAGCATAAC CTTGTGGGTC ATCTGATTTA GCCACTCTAG 4081 CCACTTTAGG TACTTTTCTA AGCCCCTTAG CTTGAGCTTG AATATCTTCT AAAACCGCCC 4141 CTTTTTCGAT GAGACGCTTA TTTCGTTGCT TTCTCTTTTC AGTATTGATG CGAGCCATTT 4201 GACGCTCTCG ACGAGCCTTA AACACTGCTT CCTTTTCTTG AAGGCGTTCA AGTTCTGCTT 4261 TCATTTTTTC AATATCAGCC ATAACAAATC CTCCTAATGT GAATAATGTT TTCTGAAATT 4321 CAAATGTTAT CTAGATTATA TGATGTTACA ATTGATTTAA CCACTACGTT TGGTCTCCCT 4381 GTTAAGGGCG CACTTATACA CATTCAAAGA ATGTAATTAC GCCTGACGGC GACGTGCGCT 4441 CTCCGAGGGG ACTTACCCAG TCGGGGCGAC TTCATCGAGA CCATGTCATG GAGATTCAGT 4501 TTCACCGAAA CGGACCACTA ACCCCGTGGA GGGGAGAAGT TTCACTTCTA GGGACCATTC 4561 CATGGAGGGT CGCTTTTTAC AAAAGCAACG CAAAACAAAA GACTAGCTCC CAAGCTTACG 4621 CAAGGTCGTT AGTCCCTAAG GAGGCAGCAC AGA (SEQ ID NO: 7). A putative L. reuteri plasmid replication origin identified based on BLAST analysis would be: 1 TTAGTCATCT TCTGTCTCCT GTTTTAGAGA ATTTTCAATC ATGTCTAATA ATGTTGACAT 61 GTCAATGTTA AATGAATCAA GGCTACCATA CCGCTTGATT TGAGTTTTAA CACTATCCAA 121 TCCATATTCT TCAAGTAATG CTTTTAATTT ACCAGTAACT TTTTCACCTA AATGCCCAAA 181 ATACTGAAGC CAGCTCTTAA GTAATTCTCG GTACTGGTCA AATTTTTGTT TTTCAGTAAG 241 CTGTTTCTCA ACTTCTTCTT GGTCCTCAGA ACCGTTAACT ACTTTCCAGA GGTCAGGGTC 301 AGTAGTACCC AACTTATAAC CAAGTACCCG ATCATATGCT CTGGCCTTTT CCTTTGGAGT 361 CAAATCAGGA TTAAGGTCAA TATTATCTAG CTTCATACGT TGGTCAGCAT AACGACCTTT 421 TTCAAAGTCA TCGGCATTCT TGGCTTCAGG TTGCCAAGTG AACTCATAGC CAACAACAGG 481 ACGTCCTCTA CCAGCTCCTC GAATAGTTTT TACGGTTAAG CCACGAATAA CAGGGGTTAG 541 CTCTTCTTTA ATTGGACGTA ACACTCTTTT TCTTACGTTA CCCTGGTCTT TCTTGTAGCT 601 CTTGGGTAGA TCTAGTTGCT TAAATAATTC GTCACTGGTT AACTTCAACC GCCCTACTGT 661 TCGATATTGT TTAATTAACA CTCTTTTTCT TACGTTACCC TGGTCTTTCT TGTAGCTCTT 721 GGGTAGATCT AGTTGCTTAA ATAATTCGTC ACTGGTTAAC TTCAACCGCC CTACTGTTCG 781 ATATTGTTTA ATCAAGCGAA ACATGTTCTT AGCATAAGCA GATTGAAGAC TATTAAACTG 841 AGCTAGTTGA AATCTTGTCC AATGACTTAA ATCATTGAAT AGCTTCTGAA ATAGAGGGTT 901 AACTTGAACA GTCAGAATCT GTTTACTCCT CTGAATCTGA AATACATTCC AACAAGCAAA 961 TTGAGTAATG GTGTCTCCAT CATCGGTGTA GGCATTAATC TCTAATAGCT TTTTATTAGT 1021 TTTCAT (SEQ ID NO: 8).

[0058] Analysis of the strain 3632 sequence revealed two agglutinin receptor precursors (ARPs), which were found only in L. reuteri strain 3632 compared to L. reuteri 2091, strain 170331, and L. reuteri ATCC 23272 (human). These agglutinin receptor precursors may be responsible for the increased levels of autoagglutination observed in this strain, and these receptors may contribute to the probiotic potential of DFM genetically modified to express them. The amino acid sequence of ARP-1 is: MNEYNAEMAKLNQGANAPVITTNSVNQALSLKPENNATVDIEALNPRITFKRVEEGTKYAGYQIFDKNNAYVNNIDGEFLRVTYTNLKNSTYKGSKISKIVVTYSDSTPTGNRITQSGLNAVTEGANDNFLVVFEDPVRGDMHSTTVTATYQYYDANGNLIDFSGTNNAWLSVGSLNFDQGNDYQGGKNEGNPTSGISEGVKLISGAQIKQLAGSSISVHDDGWAYAGFNNYSGTGMNNGINTDNGGSGWDMDGSPNAYYGAIVFQLTGSSVSLRQGLVSWGGADIASQYNNQFLNNAWFTAGTTLPETQIKQPIRKTSETHYHYNPSVIRL (SEQ ID NO: 9). The amino acid sequence of ARP-2 is:

[0059] L. reuteri strain 3632 contains eight bacteriophage-encoding loci, but only three of these loci appear to encode productive prophage. Bacteriophage locus 1 has the following sequence: 1 CTATTCAAAT TTGAAATTTT GAACAACTTT ATCAAGGTCT TCTTGTTCAA TCCCTAGATA 61 GTGGCGCGTA TTTCGTTCAG AGGAGTGATT AAATAACTGC GAAATGATTT CAACGTTAAC 121 ACCTTTCTTA TAGAGTTGTC GACCAAAAGT TTTTCTAAAA GAGTGTGTTC CAATTTTAGC 181 AACGATTTTA TTATTTTCCG TTTTTCTAGC CATTCGTTGC AACATTTCGT AAAAGCCATG 241 TACTGAAAAA TGACCTTCTT GTTTCCCAGG GAAAAGATAA TCATTCTCGT CTTTATAATT 301 CAAGTCATTA AGATAATCAA TAATTTCGGC AAGACAATTA TTCCAAAAGA GCGTTTTAGC 361 CTTACCTGTT TTTTGCTCAA TAACACGGGT TTTAGTTTTA TTTAGAACAT GACCAACCCT 421 TAACGTTACA ACGTCTGATG CTCGCAATCC GTTATTAAGG GCAATTGCAA TTAGTAATAG 481 GTTTCGGTTA ACCAATTCAG GACGCGAATG CAGCTTAATT GTCTCACGTA ACTGATCATA 541 TTCTTCGAGA GTCAAGAATT TAACATTTTC TACCCATATT TTCCGTTTAC CCTTGATTTG 601 ACCATTAGTT TTATTTTTGG GAATATAAAC TCGTTTTTTA GTTGACATAA TATTTCTTCC 661 TTTGTTAATT TGCGAGGTAA TCAACTAAAG CAUTION TTCCTCTCCT TCTTTCCGCC 721 CAGTTTCATA AAGTGCTCGA ATTTTCTTAA TATTTCCTTC AATCCGCTTA ATTTTAATTG 781 GTTTAGAGGG AAGATCTTTC CTTCACAAGA CAAACGATTA ATTTCAGCAG 841 TCTGTTGGTT GTAGAGAAGG GGACGATCAA TCCCCGCTTT AGCAAATTCG GGATAATCTT 901 FATHER GTCGTACAAC TTCTTTACAG CAGAACTAGA TGGCTTCTTT CGGTAGTTAA 961 TATCCCTGGT CCGTACAACA ACAATCTTGT CATAGCCTTG TCGTTGTGCA ATATCAAATG 1021 GAATTGAATC TGTGATCCCA CCATCAAGGC AAGGCCCTTG AGAAGTTTCC TGTGGATCTG 1081 AAAGAAATGG CATTGATGAG GAAGCTTTGA GGGCATTGGT TAGCTCCTCA CCAACAGGAT 1141 CCGTAAATAA AACTGTTTTT CCTGTTTTCA CAGAAGTAGC AACTGCTGTG AAATGAGATG 1201 CTGACCGTCG ATATGCAGCT TCATTAAAAT TCTGCCAAGA ATATCCGTGA TCTTCAAAAA 1261 GATAATCAAG ATTAATTATT TGCTTTTTAA ATACGCGAGC CATCGAGATA TATTGGCGAT 1321 CGTGCCGATG ATCAATTA ATTATTGGCAG CGCGTCCGTA TTGCTTAGAG ACGAATTA 1381 CTCCACAAAG TGAACCAAGCA GAAACGCCAA TTACACTTCG AAATTCAATA TGGTGAGCGA 1441 GAAATGTATC AACAATTCCG GCAGTATATT GTCCACGGAA TGCGCCACCT TCTAAAACTA 1501 ATGCTGCATT ATTACK ACTCCTTTTT GTCCGCCAAA ATTAGCAAAA 1561 ATGACCTAAT TTTTAGTGAG ACACTTTTTC AATAAAATTA TACAACAGTC TCACACGAAA 1621 ATTACK TTAAAAGCTT GTTATATCAA CGTTTATTCT CGGTTACCGT AAGACTCTTT 1681 TATCAAAAGA GTCTTACTGA TTTTGAAATA ACGCAAAAGT AGGGGCAAAA ACGGATTTTG 1741 CCTCTCAGAC GAACTGAAAT TCATTTTGAT GAGTACAAT TCGTCTCAGA 1801 AGAAAAACGC ATTATTGATAT CAAAAAATGA GTAAATAGAC AGTAAATTT TAATATGAA 1861 CTTTTTATGA AGAAACTATT GATAATTATT ATAAAATAGT GCACAGTTAA 1921 TTGTTAAACG TTTAGCAAAA AAGGTAAAGA AACGGGGTTA TTTCTATGCT AGAACGCAAG 1981 AAATGTATAA AATTGGTAAA AATTGGGCAG TTGTTACACT TTCTACGGCT 2041 GCACTGGTGT TTGGTGTAAC AACTGTAAAC GCATCCGCAG ACACGAATAC TGAAAACAAT 2101 GATTCTTCTA CTGTACAGGT TACAACAGGG GATTATGATA TTGCTGTTAA AAGTGTGACA 2161 CTTGGTAGTG GTCAGGTTAG TGCAGCTAGT GATGCGACTA AAAATTCTGC TAATGCAAAT 2221 AGTGCTTCTT CTGCCGCTAA TACACAAAAT TCTAACAGTC AAGTAGCAAG TTCTGCTGCA 2281 ACAGCTTCAT CTACAAGTTC AGCATCTTCA TCAACTAACA CAGATAGTAA AGCAGCTACA 2341 GAAAATACTA ATGTAGCCAA AGAGGATGA ACACAAAAAG CTGCACCCGC ATGTCC 2401 TCTGAACCCA AAAAAGAACC AGCTGTAAAC ACTAATGATT CTTCAGCTGC CAAAAACGAT 2461 GATCAACAAT CCAGTAAAAA GAATACTGCC GCTAAGTTAA ACAAGGATGC TGAAAAACGTT 2521 GTAAAAAAGG CGTGGATTGA TCCTAATAGT TTAACTGATG ACCAGATAA AGCATTAGT 2581 TAAATAAGAT GAACTTCTCG AAAGCTGCAA AGTCTGGTAC ACAAATGACT TATAATGACC 2641 TTAAAAAGAT TGGTGAGGCT TTAGTTGATC AAGATCCTAA ATACGCTATT CCTTATTTTA 2701 ATGCAAGTCA AATAAAGAAT ATGCCCGCTG CATATACTAG GGATGCTGAA ACAGGTGAAT 2761 ATGCTGATTT AGATATTTGG GATTCATGGC CAGTTCAAGA TCCAGTGACT GGTTATGTTT 2821 CTAATTGGAA TGGCTATCAA CTTGTGATCG CTATGATGGG ACGGCCTCAT CACGAAGATA 2881 ATCATATTTA TTTACTTTAT AATAAGTATG GTGATAATGA TTTTTCACAC TGGCGAAATG 2941 CAGGATCTAT ATTTGGATAT AATGAATCTC CACTAACACA AGAATGGTCC GGGTCTGCTA 3001 TTGTTAATTC TGACAACTCT ATTCAACTCT TTTATACTAT CAATGATACA AATAATGCTA 3061 TTAACCATCA AAAATTAGCA AGTGCTACTA TGTACTTAAC AGCCGACAAT GATGGTGTCC 3121 ATATTAATAA TGTAGAGAAT AATCATGTGG TATTTGCAGG TGATGGTTAT CATTACCAAA 3181 CTTATGATCA ATGGAAAGCT GCAAATAGTT TTGCTGACAA CTACACTTTG CGGGATGGAC 3241 ATGTTGTACA AATGCCAAAT GGTGATCGGT ATTTAGTATT TGAAGGAAAT ACTGGAACTG 3301 AAAATTATCA AGGTGAAGAT CAATTATATA ATTGGTCAAA TTATGGTGGT AACGATCGCT 3361 TTAATATTGA AAGCTTGTTT CATCTTTTAA GTAGTGATGT TGATTATAAA AAAGCTATCT 3421 TTGCTAACGG GGCACTTGGA ATTATTAAAC TAACGAATGA TGAAAAGAAC CCGCAAGTAG 3481 AAGAAGTATA TACTCCATTA GTTACATCAA ATATGGTTAG TGATGAACTT GAACGTCCTA 3541 ATGTTGTTAA ACTTGGAGAT AAGTATTATC TATTCTCGGC TACACGTTTA AGCAGAGGAA 3601 CTAATATCGA TACTCTTAAT AAAGCTAATA AAGTTGTCGG AGATAATGTT GCAATGATTG 3661 GTTACGTAGC CGATAGTCTT ACAGGTCCAT ATAAACCATT AAATGGTTCA GGGGTTGTAG 3721 TGACAGCTTC TGTTCCTGCC AATTGGCGTA CCGCTACTTA TTCTTACTAT GCTGTTCCAG 3781 TAGAAGGAAA AGAAAATCAA TTACTCATTA CTTCGTATAT GACAAATAGA GGCGAAGTTG 3841 CTGGAAAAGG TATGAATTCA ACATGGGCAC CAAGTTTTAT TGTGCAAATT AATCCTGATG 3901 ATACAACTAT GGTATTAGCT AAAGTAACTA ACCAAGGGGA TTGGATTTGG GACGAATCAA 3961 GTAACAATAA TAATATGTTA GGAAACATTC AAACAGCTGC TTTACCTGGG GAATTTGGTA 4021 AACCAATTGA TTGGGATTTA ATTGGTGGTT ATGGATTAAA ACCGCATGAT CCTGCTACAC 4081 CAAATGATCC TGAAACGCCA ACTACACCAG AAACCCCTGA GACACCTAAT ACTCCCGAAA 4141 CACCAAAGAC TCCTGAAAAT CCTGGGACAC CTCAAACTCC CGATACACCT AATACTCCGG 4201 AAGTTCCTTT AACTCCAGAA ACGCCTAAGC AACCTGAAAC CCAAACTAAT AATCGTTTAC 4261 CACAAACTGG AAATAACGCC AATAAAGCCA TGATTGGCCT AGGTATGGGA ACATTGCTTA 4321 GTATGTTTGG TCTTGCAGGA ATTAACAAAC GTCGAGTTAA CTAAATACTT TAAAATAAAA 4381 CCGCTAAGCC TTAAATTCAG CTTAACGGTT TTTTATTTTG AAAGTTTTTA TTATCGAAAA 4441 AAACAAATCC TCGTTAATCC TTTAATGCAA TTGTTGTAAA ACCTTGCGAC AGTAATAACA 4501 GTGGATTTGC CCATCTTTGT CAGCTAACTT CCGTGCATGC ATTGCAGAAA AAGTATAGTG 4561 CTCATGACAA AATGGACAAA CATATTGCTT TTTCCCAAAT AGTGAGGTAA TAAAGCCCAA 4621 AATTTTCTCC TCCATAAAAA AATTATACAC CCCTTAACAT TATAGCGAAG ATTATCTTTA 4681 TAGAAAAGGC TTTTATTCAT TTGTTTTTTT ATATGAAGTT TCACTAATTT CTTTAAGAGC 4741 ATCACGCTGC TGTTTCTGGT CAACGTGAGT ATATAAATCG GTAGCAGATG TTCCTTTTTG 4801 TCCCAACTGT TGGGCCACTA ATACTTGATC TTTCGTTACC TCATACATTT CAGAAGCAAG 4861 GGTGTGCCGT AATTTATGGG GAGTAAGAGG ATGGCCAAAT GCGGTTGAAT ACTTTTTGAC 4921 CATTTTTTCA ATTGCATTAG CTGTCATCCG TCGAGTTTGC TTGTGATAAA CGGTTAGGA 4981 GAAAGCAGTA TCCTTTTTTA AAGCGTGGTA TCGTTGTGCA CGAATCGCTT GGTAAGTTTG 5041 TACCCAAG GAGCAATTGG TACCGAATCC CTCTGGCCAC CTTTTCTTGT 5101 TACATCTAGC AGCGATTGTT TTAAGTTTAA ATCACCAAGG TTTACATTTG CCGCCTCGGA 5161 TACCCGGACG CCTGTTCCTA AAATAAGAGC AATAATTGCA ATATCTCGTT CCTTATTGAC 5221 CTTATAAGAG GGGAGAGCTC TTTTATCACA TTTATTAGGG TATTCTTTTT CAATGAAAGT 5281 AATAAAATCA AACTTCATTT GTCCCCGGTA CATGTGTGAA GCCAGCGTAT GAGCCCGATA 5341 ATTTAATGTT TTTGTATCAT TAAGGGAGTC AATTTTCAGC ATTACATTAC GGTCAAAATA 5401 AGATTCACCA TTATTGTTAT CTGCGGTAAC TGTTAAAAAT TTATACAATG ACCTTAATGC 5461 ATTATTAGAT CGATTGATTG AAGTAGATATTTAACCGT CCTTGTGCAT TGGTAGTATG 5521 CTGCAAATAA TCGATATACA ACATTACATC GCTACGCCGT AGATTCGCCA GTGTATCAAT 5581 TGGTAAGTCC TTATTAGAAT TAACAGAGAC GAGTCCACTT GACCGTAACC AATCAAAGAA 5641 TCGACGGATT TCAGTTAAGT ACTGATAGGT TGTTGTGACT GCATGGTTGG TCCCTAAATA 5701 ATACTCGTTA ACATAATCAG GAAGGTTCTG AAGCTCCTCT TGAATTAGCT TTAAATATTT 5761 ATCTGCTTCC ATTTTTATAT CCTCCTTGAT ACTAAAAAGA GTCGCTTGAA AGAAAACTTT 5821 CAACGACTCT CTAAACCTAT CGGGAAAACA GGATTCGAAC CTGCGACCCC CTGGTCCCAA 5881 ACCAGGTGCT CTACCAAGCT GAGCTATTTC CCGTTAATAA CGAACAAATA TTATTCTACC 5941 AATTCTCAAT TAATTAGTAA AGGAATATTT TAATTTAAAG TGATTAATAG TTAATGATTA 6001 AATGACATAA TAGTAAAATT CCTATTAATT GCAAAAAAAT CATGATTAAC CGAAATCCTT 6061 TTCTAGCATC TAATGAAGAT GATAAATAAT TTTATTTTCG ACTAGTTATA AAAGATACCT 6121 TTCCGAAAAT AATTTGACAT TCAAAATACT TTTGAATATA ATTTGATTAT CGAATATTTT 6181 GATACTCGAA ATATTTTCCG AAGGCAGGTG AATCTTTTTG GCAATAATGA ATGCGCAGGA 6241 GATTATGGAA TTAATTCCTA ATCGATATCC GATTTGCTAT ATCGATTATG TAGATAAATT 6301 AGTTCCTGAA GAAAAGATTA CCGCAACAAA AAATGTCACA ATTAATGAAT CATTTTTTCG 6361 CGGTCATTTT CCTAATAATC CTGTTATGCC TGGAGTTTTA ATTATCGAAA CATTGGCCCA 6421 AGCTGCTTCA ATTTTGATAT TAAAATCACC GCATTTTTAT AAGAAAACAG CTTATCTTGG 6481 CGCAATTCAT AAAGCAAGGT TTCGACAAAT GGTCCGTCCT GGTGATGTAT TAAAACTAAA 6541 CGTTGTTATG AAAAAAGTTC GATCATCAAT GGGGATTGTA GAAACACAAG CGCTTGTGAA 6601 CGGCAAATTA GCTTGTAGTG CGGAGCTTGT CTTTATCGTT GCTGAACGAG AAGAAAAGAT 6661 TTAGCACGGT GAATCATTAT CATTTATAAT ATATTTTGAT AATCAAATTA TTCGGGCTAT 6721 AGAATAAAAT TGAAGGGAAG AAATATATTA TGAGTAAAGA TAATGATTAC GAAAAAATTA 6781 ATAAAGGATT AATCAAAGTT TATTCCGGAA TTCTATGGAT TGAAGAAAAT GAATTGCGGA 6841 AAAGTACATT CAATGATTTA ACAATTAAAG AGATGCATGC AATTGATGCA ATTACGATGT 6901 ATAACCATCA AACAATTTCT CAAGTAGCAG AAAAGCTTCA TCTAACTCCA GGAACAATGA 6961 CTTCAATGGC TGATCGTTTA ATTCGAAAAG GATATGTGGA AAGAATTCGT GATAAAGATG 7021 ATCGCCGCAT TGTTCGGTTA TGTTTAACCA AAAGAGGCCG GGTACTATAT CGTGCGCACC 7081 GGGCCTTTCA TAACATGATG GTTGAACGTT TTCTTAAAGG AATGGATGAT TACKAAATGA 7141 AGGTTGTTAA AAAAGCCTTG CAAAACTTAG AAGATTTTGT GGATGAGCAT GCTTAGAGAT 7201 CONTACT AACATTGCA AACATTGCA CONTACT CTGCACCC 7261 CTTAAAATTA CTTACHTAG ATTATCAACT CATCHTAG CTTCATGA GTGGATTAAG 7321 ACGCGGACTG GAATTCATCA ACGTTATATC AGCAACACTG AAAATACTTC AGACTTAGCT 7381 GTCAATGTTG GTACCCAGTT ATTGACTAAT GCCAATTTAA AGGCAACTGA ACTTGATTA 7441 ATCATTATTG CAACATGTC TCCTGATGCC TATACTCCTT CAACTGCTGC TATTGTTCAA 7501 GGAATTAG GTGCGAAAAA TGCAATTGCG TTTGATATCT CAGCAGCTTG TACTGGTTTT 7561 ATCTATGCCA TTAATACAGC TGAATTAATG TTGAAAAGCT CTCATTGGAA AAATGCAATG 7621 GTAATTGGTG CACAAGTATT ATCAAAACTG ATTGATTGGC AAGATCGAAG TACTGCCGTA 7681 TTGTTCGGCG ATGGGCTGGC GGAGTGTTAC TTCAAAAGAC AACTACAACA ACCCCTTTAA 7741 TTCTCGGCCG TGATCTCCAT ACATTTGGTG ACTTAGGAGA TAAAATTATT GCCGGAAAAA 7801 AACGCCTAA AACTGGCTTC CCTAAAAAC TAACATCCCT TTCACCATTT ACGATGGCCG 7861 GCCGTGACGT ATACCGCTTT GCCACTCATG AAGTACCACG ATCAATCACT TCTGCCGTTC 7921 AACAAGCTAA TTTGAAATTA GACGATATCG ATTATTTTTT ATTACATCAA GCAAATGAAC 7981 GGATAATTAC CCAAATTGCA AAGAGACTGG CGCAACCAAT TACAAAGTTT CCAATGAATA 8041 TTAGTGATA TGGGAATACA GCTGCCGCTA GTGAACCAAT TTTATTGACT CAAGCTATTG 8101 CTCATGAATT GATTAAACCA GGTAACATTA TTGCAATGAG TGGCTTTGGT GGCGGGTTAA 8161 GTACAGGAAAC AATAATTTTA AACTATTAAT AGAGAAAGAA GAATGGATAT GACTAAAGAG 8221 GAAATTTTTA ATACTGTAAA AACTATTACT GTTGATGAAT TAGATGTTGA CGAAAATCGT 8281 GTAACAATGG ATGCACGAAT CAAAGATGAT CTTGATGCTG ATAGTCTTGA TGTTTTTGAA 8341 ATTATGAATG AGCTTGAAGA TAAGTTTGAG ATTGAATTAG ATGCCGATGA AGGAATCGAG 8401 ACTATTAGTG ACGTTGTTGA TTTCGTAAAG AAACAGTTGG ATGAAAAAATA ATGTACTACG 8461 GAATATTATT TAGCGGTCAA GGTGCACAGC GATCGGGAAT GGGAGTCGAG CTTATGGCCG 8521 ACTCCCTTTT TTCAAGGATT GTTAGTCAGG CAAGCGCTGT TTGTGAACTT GATTTGCTCA 8581 AAATTATGAA AAACGAGCAT AAGGAGTTGA ATAAAACAGC ATATGTTCAA CCAGCAATTG 8641 TAACAGTTAG TTATGGAATC TACCGAATGT TAAAACGGGA TTTACCTCAA CTACCAATTA 8701 AAGGGATGAT TGGCCTATCT TTAGGCGAGT ACGCTGCTTT AATTGCTAGT AATGCACTTT 8761 NEAR CATTTGAAA TTAGTTGCGG ACCGTGCTCA CTTTATGCAA CAAGACGCGG 8821 ATAGAGAAAT AAGTACATTA GCAGCTGTCC TTGATCCTCA ACTTCAAGAG ATAAAAGAAC 8881 TAATCACCGC TCAACAAGAA AATGGTCAGC GAGTTTATAT TGCTAACTAT AATTCACCAC 8941 GACAAATCGT AGTGGGCGGG GCATTAACG CTTTAAAGGC TACCCTTAAA AAGATTGAAG 9001 AGGACAAGCT TGCTAAAAA ACGATCCTGC TCAAAGTTAA TGGTGCATTT CATACTCCCT 9061 TCTTTAACGG TGCACGTCAA CAGATGCATA ACCGGTTACA AGCAGTCGAC TTCCATGAGC 9121 CACAGATTGA AGTTATTAGC AATACTACTA ACAGCTTGTT TCATTGTGAG GATCTTCCAG 9181 GAATTCTTGA AAAACAATTA GCTGTTCCAA CACACTTTGG AGCTAATGTT AAGGAATTAG 9241 TCAAGCACGC GAAAATTGAC ACAATATTGG AAATTGGTCC TGGAAAGACG TTATCTCGCT 9301 TCGCTCACCA AGTTGACCAG CACTTAAATA CCCAACACAT TGAAAATCTTT GCTGATTATG 9361 AAAAATTTAT AAAGGAGCAA AAAGATGGAA CTGACAGATA AAGTCGTTTT TATAAGCGGA 9421 AGCACACGCG GGATTGGGGC GGCTACTGCA TTAGAGTTTG CTAAGGCTGG TAGTCGGCTA 9481 ATCCTCAATG GGCGGCAGGA TAACTTACCA AAAACGTTTA AAGAAAAGCT AGATCTACTA 9541 GGGGCGGATT ATCACTATCT TAAGGGCGAT ATTGCAAATG AAGAATCAGT TAGTGAATTA 9601 GCAGCAGCGG CTTGGCAAAT ATACGAGAAG ATCGACATTC TTATCAATAA CGCGGGAATC 9661 ACGAATGATA AGTTAATGAT GGGAATGAAA GCGAGCGATT TTGACCAGGT CATCAATGTT 9721 AATTTACGCG GAACATTTAT GTTAACGCAA CCTATTTTTA AGAAGATGCT CAAAAAAAGA 9781 GTCGGTTGCA TTATCAACCT TGCTAGTATT GTGGGTCTCC ATGGTAATAC GGGACAAGCT 9841 AATTATGCGG CAAGCAAGGC AGGTATCATC GGCCTTACTA AATCTATTGC CCAAGAAGGA 9901 GCACGCCGTG GAATTCGTTG CAATGCGATT GCTCCCGGAA TGATTACTAG TGATATGACT 9961 GAAAAATTAT CTGAGCGAGT AAAAGAACAA ATTCTCAGTC GCATCCCCCT CAACCGCTTA 10021 GGACAGTCAG AAGAAGTTGC TAAGACCGCA AAATTTTTAG CAGAAAACGA TTATTTGACT 10081 GGTCAAACCA TTGTAGTTGA CGGTGGCATG ACAATTTAGG AGGAACTAAA TGACAAGAGT 10141 TGTAATAACA GGAATGGGTG CTGTTGCTCC TAATGGTAAC GGTATTCAAG AATTTATAAG 10201 TAATAGTTTT GCAGGCAAAG TTGGAATTAA AGCGATCAAG AAATTTGATG CCAAGTCGAC 10261 AGGAATTACC GTGGCAGGTG AAATTGACGA TTTTGACCCT AATGATGTCA TTGGAAGGAA 10321 AGCCGCGCGC CGAATGGATC TTTATTCTCA ATACGCCTTA CAAAGTGCGA TTGAAGCAAT 10381 GGAAATGGCG GAGATTAACG AAACAAATAC CAAGCCAGTC GACATGGGTG TTATCTATGG 10441 ATCTGGAATT GGCGGTTTGA CAACTATTCA AGAGCAAATT ATCAAAATGC ATGATAAGGG 10501 TCCTAGACGG GTATCACCAA TGTTTGTTCC AATGTCAATT GCTAACATGG CAGCCGGTAA 10561 TATTTCCATT CACTTTAATG CGCAAAATAT TTGTACATCG ATTGTGACTG CTTGTGCCAC 10621 TGGAACTAAT GCAATTGGTG AAGCCTTTCG TCAAGTTAAA GCAGGTCGCG CTAAAGTAAT 10681 GATCGCTGGT GGATCAGAGG CTTCGGTGAA TGAGATCGGG ATTGCTGGTT TTGCGGCATT 10741 AACAGCCATTA TCACAAGCAA CTGATCCGCT TAAAGCTTCT TTGCCATTTG ATAAGGCACG 10801 TCAAGGATTT GTTTTGGGTG AAGGCGGTGC AACACTTGTT TTAGAGGATC TTGAGCATGC 10861 GCAAAAACGC AGTGCTAACA TTCTTGGTGA GATTGTCGGT TATGGTGCTA CCTCGGACGC 10921 TTACCATATT ACATCCCTG ATCCAACTGG TGCAGGGGCG GCAAGAGCAA TGGAACTGGC 10981 AATTAAAGAA GCTGGAATTA GTCCTAGCGA AATTTCCTAT ATTAATGCCC ACGGAACCGC 11041 TACTCATGCT AATGATGAAG GCGAATCCAA AGCAATCAAT CAGGTATTTG GTTCCGATAG 11101 TAATGTTCGC GTTAGTTCAA CGAAGGGAAT GACCGGCCAT TTGCTTGGGG CTGCGGGCGC 11161 AATTGAGGCA GTCTTAACAG TAGCCGCTTT ACAAAAGGGA CAATTACCGT TGAATATAGG 11221 TTGCTTTAAT CAAGATCCAA AATGCTCGGT TAACCTTGTG ACGGCAGAAA ATAGGAACGC 11281 CTCAACCGCC CGTTACGCAA TAAGCAATTC TTTTGGTTTC GGTGGTCATA ATGCTGTTTT 11341 AGCCTTTAAG AAATGGGAGT GATCTATCTT GGAATTTAAA GAAATTCAAA CATTAATGCA 11401 AAATTTTGAA GATTCTGATA TTCGTGAATT AGAAATAAAT CAAGATTCCT TTCAGCTCTA 11461 TTTAAGCAAA AATAAGCAAA CCCACAAGCA TGAAAATCTT ATAACAACCG AAAAAACGA 11521 GCAAACGACT TCAGCTAAGA AAAAAGCAAA CGAACAACTA ACTTTACCTT CGCAAAATAT 11581 AACTGCGCCC CTAGTCGGAA CAGTCTATCT CCAACCAACC CCCGATGCAG ATCCCTATGT 11641 TAAAAGTGGC GACCACGTAA AAAAGGGGGA TGTTGTTTGT GTGATTGAAG CAATGAAAAT 11701 GATGACAGAG ATAAAAAGCC CTTTTAACGG AACCATTACT TCAATTTGTG TAAGCAATGA 11761 AGAATTAGTT GAAGTAGAAC AACCGCTTTT CTCAGTTCAG GAGGATAAAG ACAATGCCTA 11821 ATAAAACTTT AGATATAACT GAAATTCAAA AAATCCTTCC GCATCGTTAC CCGATGTTGC 11881 TAATTGACCA AGTTGATGAA TTAATCCCTG GTAAGAAGGC CATTACACAC CGTAATGTCA 11941 CGATTAATGA AGAGGTTTTT AATGGTCATT TCCCCGAAAA TCCAGTTTTA CCAGGAGCAT 12001 TGATTGTTGA ATCATTGGCG CAAACAGGTG CCGTCGCTCT CTTATCTCAA GAAGAGTTCC 12061 AAGGGAAAAC AGCCTATTTT GGTGGAATTC GGTCAGCAGA ATTTCGTAAG GTAGTCCGTC 12121 CGGGCGATAC GTTAAGGTTA GAAGTCAGAC TAGAAAAAGT TCACAAAAAT ATTGGAATTG 12181 GTAAAGGCAT TGCAACGGTC GATGGCAAAA AAGCCTGTAC AGCCGAATTA ACTTTTATGA 12241 TTGGGTAGGT GGTTTAATGT TTTCCAAAGT ACTAGTGGCT AATCGTGGTG AAATTGCTGT 12301 CAGGATAATA CGGTCATTAC GGGAGCTAGG AATTAAGACA GTAGCTATCT ATTCAACTGC 12361 AGACCGCGAA AGTCTTCATG TTCAACTAGC GGATGAAGCT GTATGCGTTG GAACTGCCCG 12421 GGCCCAAGAT TCATATTTGA ATGCGAAAAA CATTTTAGAA GCTGCTCTTG GTACAGGTGC 12481 CCAGGCAATC CATCCTGGCT TTGGCTTTCT ATCAGAAAAT GCGGAATTTG CGACAATGTG 12541 TGAAGAATGC GGAATTACGT TCATCGGTCC CCAAGCCTCA GTGATTGACT TAATGGGAAA 12601 TAAGGAGCAT GCACGGGAGC AAATGAAAAA ATCAGGGGTG CCTGTGATTC CTGGAAGCGA 12661 TGACTATATT ACCAATGTTA ATGACGCTGT TGAGGTCGCA AACAAGATTG GGTATCCAAT 12721 TTTGTTAAAA GCAGCTGCTG GTGGTGGCGG TAAAGGGATC CGACGAATTA ACGATCATAA 12781 CCAGATGCGG CAAATATTTA GCGAGGCCCA AAACGAAGCC CGACTTTCGT TTAATGATGA 12841 CCGAATGTAC CTTGAAAAGA TTATGGAGAA TGTTAAAACAC ATTGAGGTCC AAGTATTTCG 12901 TGATAATTTT GGCAATGCCG TTTTCTTTCC TGAACGTGAC TGCTCGATTC AACGGAATAA 12961 ACAAAAATTG ATTGAAGAAA GTCCTTGTGT CCTAGTAAAT GAACAAGAGC GAAAAACGCT 13021 AGGACAAATT GCAATGCGAG CCATTAATGC GATTAACTAC CATAATACGG GGACAATAGA 13081 ATTTCTAATG GACAAGGACC ATCACTTTTA CTTTATGGAA ATGAACACTC GTATCCAGGT 13141 TGAACATACA GTGACGGAGA TGGTAACTGG GATCGACTTA GTGAAGGCAC AGGTTATTGT 13201 CGCTGCGAAT GAACCACTTC CCTTTACCCA ACAGGATATT CAGGTTCATG GACATGCAAT 13261 TGAGTGTCGG ATAAATGCTG AAAATCCTAA ACAAAACTTT ATGCCAGTGA CTGGGACGAT 13321 TAATTACTTA TATCTTCCAG TCGGTAATTT GGGGATGCGC ATTGACACTG CTATTTATC 13381 TGGCAGTAAG ATCACTCCTT ATTATGATTC AATGATCGCT AAGGTAATTG CCCTTGGTCA 13441 AGATCGCCAA GAAGCTATTG AAAAAATCAA ACGACTTTTA AATGAAATGG TAATTACGGG 13501 CGTAACGACC AATCAAAATT TCCATTTAGC AATCCTAAAC AATCCTAAAT TTTTGGCAGG 13561 AACAGCTTCA ACAACGTTTC TTGAAGACTT CTTCTTGCCA CAATGGAAAA AGGAGCTGAC 13621 AGCGTGAAAT TATATGATCA AAATAATACT TTAAGTGAAC GGCACATCAA AGCAGATAAA 13681 AATGCTGATG AAAGGGTCCC AGATCAAATG TGGTTAAGGT GTCCACATTG TCATCAATTA 13741 CTATTCGCCA AGCAGTTAAC ACAATATGCT GTTTGTCCCA ATTGTGACTA TGGATTACGA 13801 ATACCTGCCC GCCATCGACT CTCGTGGTTA GTAGATTCAT TTAAAGAATT CGATAAGGAT 13861 CTCCAGACAA AGAATCCGTT ACATTTTCCT GGATACCAAG AAAAAATCAG CAAACTTCAA 13921 AGCAAACTA AGCTGAATGA TTCAGTCCTA ACTGGTGAAG CTTCAATTAA TGATCAGCTA 13981 TTTTCACTAG GTATTATGGA TCCAACATTT ATTATGGGAT CCCTCGGAAC TGTTACCGGT 14041 GAAAAGATAA CGCGCTTATT TGAATATGCA ACTATCCATC GTCAAGCAGT AGTACTATTC 14101 ACTGCTTCAG GCGGGGCACG GATGCAAGAA GGAATTATGT CGCTAATGCA GATGGCGAAG 14161 ATTTCACAAG CAATAAATGA GCATGCTGCT GCCGGCCTTT TATACATTGT GATCTTAACC 14221 GATCCAACAA CTGGTGGAGT AACAGCTAGT TTCGCAATGG ACGGAGATAT TATTCTCGCT 14281 GAGCCCCATG CACTTGTTGG CTTTGCAGGC CGTCGAGTTA TTGAACAGAC GATTCATCAG 14341 CAAATTCCTG TTGATCTCCA ATCAGCTGAA AACATCCTGC ATCATGGATT TATTGATCGA 14401 ATTGTAAAAC GTCAAGATGA AAAAAAGCTG CTTGAATGGC TATTAAAAC AGGGAGCTT 14461 GCTAATGAT COMPETITION CHANGEGCGA COMPETITION CGTGCTCGCA COMPETITION 14521 AATTACGGGG ATGGAGATTA TTCAAAATGT TTTCCCAGAT TTTGTTGAGT TGCACGGCGA 14581 CCGGGCAGGC GGGGATGATC CTGCAATCGT TGGTGGAATC GCTACTTTCC ATCAGCAAGC 14641 AGTTACCGTC ATTACKACTG ATCGAGGAAA ACACACAGAA GAAAAAATCA ATTACKTT 14701 TGGCTCACCA ATGCCTAGTG GTTATCGCAA GGCACTCCGC TTAATTAAGC AAGCAGTTAA 14761 ATTTAAGCGA CCTGTATTCT GTTTTGTTAA TACCGCAGGA GCATTTCCTA GCAAGGAAGC 14821 CGAAGAAAAT GGGCAAGGAA GTGCGATTGC CCAAAACATT TTACAAATAA GTCAGCTTGC 14881 CATTCCAATT ATCACGATTA TTTATGGTGA AGGAGGTAGT GGGGGAGCCT TAGCATTGGC 14941 ATGTGGAGAT GAAGTATGGA TGTTAGAAAA CAGTACTTAT TCTATTTTAT CTCCTGAAGG 15001 GTTTGCCTCC ATCATGTGGA AAGATAGTAC GAAAGCAGAT AAAGCGGCAG AATTAATGCA 15061 AATGGTGCCG CAAGCTTTAT TAAAACAAGG GATTATCGAA GGAATTATTC CAGAAAGCGA 15121 AGAGCATCGT AAAACTTGCA AAAATATCGA GCAGGTTTTA CTAAAGCGAT TAAACAAGCT 15181 GCAAGAATTA CCGCCAAACC AACTTCTAGC AAACAGAAAA AAACGTTATC GAAAGTTTTA 15241 AGGAGGATAA TATGGGAAAT ATATTAACAG GAAAAAAGAT CGTTGTTATG GGAGTAGCTA 15301 ATAAGCGTTC TATTGCATGG GGATGTGCAC AAATGATGGC TGAACAAGGT GCCCAAGTTA 15361 TCTATACTTA TCAGAATTCC AGAATGAAAA AAAGCTTACA ACGGTTAGTA GATGATGAAG 15421 ATCAATTAAT TGAATGTGAT GTAGCAGATG ATGAAAGTAT TGACCAAGCC TTTACGATTA 15481 TCAAGGAACG TTTTACAAAA GTAGATGGAA TTGTACACGC AATTGCTTTT GCAAAAAGAG 15541 AAGAATTAGC TGGTTCAATC CTTGGTGCTA GTCGCAAAGG TTATGCAATT GCGCAAGATA 15601 TTTCGTCTTA CTCCCTTATT GCTGTCGCTA AGGTTGCTAA TGAGTTAAAT CTATTAAATA 15661 ATCCTGCAAG TATTGTTACC TTAACTTATT TTGGCTCAGA ACGTGCTATC CCTAACTATA 15721 ATGTAATGGG AATTGCTAAA GCTGCCCTTG AAGCTAGTGT TCGCTATTTA GCACGGGATT 15781 TAGGACAAAA ACGAATCCGT GTTAACGCAA TCTCTGCTGG CGCGGTTAAG ACATTAGCAG 15841 TTACAGGTAT TAAAGGTCAT GATGAACTTT TAAAGATGTC CCAAGCAAGA ACTGTTGACG 15901 GAGAAGATGT GACTATTAGC GAAATTGGGA ATGTGTGTGC ATTCTTAATG AGCGATTTAT 15961 CAACTGGAGT TACTGGCGAC ACCATTTATG TTGATAAGGG GGTACATTTG ATTTAAAAAT 16021 ATAAATTTTA AAGACTGAGA AATGAGTTTT TTTCAGTCTT TTTGCTGTCT TTTAGAAGGA 16081 AAACATAACA ATAGCAAGAA CTTTTTTTAA TTTTTTCTAA AAAGTTCTTG CTATTTTATA 16141 GCTCAGTTGG TATTATTAAT AACGTTGTGA AAGACGAGTT AATAATTTTG AGAAAAATTG 16201 TTTAATATAT TTAAAAATGG CCCGTTAGTC AAGTGGTTAA GACACCAGCC TTTCACGCTG 16261 GTATCGTGGG TTCAAATCCC GCACGGGTCA CTTTTGCGGA OWNER TGGTOWNER 16321 TCACCTTGCC ATGGTGGGGG TCGCGGGTTC GAATCCCGTC TTCCGCTTAG CCAGTTCTAT 16381 TATGCCGGGG TGGCGGAATT GGCAGACGCA CAGGACTTAA AATCCTGCGG TTAGTGATAA 16441 CCGTACCGGT TCGATCCCGG TCCTCGGCAC TATTTCGGGA AATAGCTCAG CTTGGTAGAG 16501 CACCTGGTTT GGGACCAGGG GGTCGCAGGT TCGAATCCTG TTTTCCCGAT CTGGCTAAAC 16561 AGCTAAGAGG TAATCTTCTT AGCTGTTTTT TTGGATATCT GTCAACTGGT ATGGTTGACT 16621 AAAAATTTTT TTAGTGCGCC CGGCATGGGT ATTAGCTAGG TGGTGAAAGT CCGCTATGGG 16681 CCGTAGTAGT CGGAACCATG AGCTGAGGAC AAGGGTGTCC ACCGTGAGGT GGAATCTGAA 16741 GGAAGTCTAA GGCAAAGTAC TGCATCGATG AACAAGAAGT AGCTATAAGG CTGAAATTAA 16801 CTGGATAAGG CTGCTAGACA AGTTGAAGTC CAATACTACT CGAAGTTGGT CTCAGTAAAG 16861 CTAACGATGA CATGGTACGA AAGCTAATAT TCTTACCCGG GGAGATCTGG CCTACACGTT 16921 TCCGACAAGC AGTACTAACG CAGCCATTAA TTAGTTTTTT GAAATAAAAT AAACTTTTTT 16981 GAAAAAAGTA TTGCTTTTTA TAGGATAACT TGATAATATA ATATTCGTCG CTGATATGCG 17041 GGTATAGTTC AGTGGTAAAA CCACAGCCTT CCAAGCTGTT GTCGCGAGTT CGATTCTCGT 17101 TACCCGCTTT TAATTAATTT AATATGGCCC GTTAGTCAAG TGGTTAAGAC ACCAGCCTTT 17161 CACGCTGGTA TCGTGGGTTC AAATCCCGCA CGGGTCATTT TTGGAGGATT AGCTCAGTTG 17221 GGAGAGCATC TGCCTTACAA GCAGGGGGTC ACAGGTTCGA GCCCTGTATC CTCCATTGAA 17281 CATTTTAATA AGTTGTTCAA CATTTTAATATAATTGGGCT ATAGCCAAGC GGTAAGGCAA 17341 CGGTTTTTGG TACCGTCATG CGCTGGTTCG AATCCAGCTA GCCCAATTAG TCTAAAACAG 17401 TGAGTAAAAA TTACTCGCTG TTTTTTATTA GAAAAAATAG GCAATCTAAT AACGTAGGCT 17461 AAAAGCGAAC ATCATTGGAT TGCCCAATAA TTAGCATAAT TTATTCACGT CGTAACATAA 17521 TATGCCAGAC AAAGAAGCCG ACTCCAATAA TTAACGCCAA CCATGCCCAT AGTTGCAATG 17581 PRICE AGTACACGTT AACAAGCCTA AAACCCAACT PRICECATC ATCGATAATC 17641 CAGCAATATC GCCACCTAAA CCATCAATAC CACAAGTAGC GATATAGACG ATTCCTGATG 17701 CCAGATATAA TAGCGAAACA ATTAATTCGG CTGTTCCGGC ATTGCAGGAT 17761 TAGTCCC AAAACCTCCT CAAGTCTTAT TCTACCCGGA TGATTAGAT TTATAAAGA 17821 TTACAGTTTT TCTATTTACA AATAGAGCAG GGGGAACAAA AAATCAAACC AGAAATTATC 17881 TTCTGATTTG ATTGGATCTT ATTTAGTTGT ATCTTTTACT TTTTTCAAGG CTTCTAAAAA 17941 TACTTCATAA GGTTGTGCAC TACTTCATAA TTAATCACAA ATAGCGGTGC 18001 ACTTGGCATT CCAATCATA ATGCGCGCCG TTCATTTTTT CGAACTTCAT CTTCATACTG 18061 ATTAGATTCA AGAACTTTTT TAACATCAGC AACAGGTAGT CCGATTTCAT TCATTGCAAC 18121 OWNERCT TCATAGTCCG CGATTGATTC ATTATCATTA AAATAAAGTT GATAAAGACG 18181 TTTAACAGCC TTATTAAGTA ATGCTTGGTC ATTTAAACTC TCAATGTATT TTATTAAGCG 18241 ATGAGCAGCT AATGTATTAA CAGGAATCGC ATTTTCCATC TTAATTGGTA AATCAATATC 18301 GGCAGCAAGT TGATCAATTT TATGTATTTG TGTAACAGCT TCTTGCTTAG TTAGTTGATG 18361 AGTTTTTGCA TAATATTCTG TCATTGATAA ATCAGTTGTT GTTGGCAACG TTGGATCTAG 18421 TTGAAATGAC ATAAATTTTA ATGGTGTCTG ATCGGCAATC TTTAATTCTT TAAGCGCCCG 18481 TTGTAATTGT GTAATTCCCA TATAGCAATA TGGGCACGCA ATATCAGCCC TATATTGAAT 18541 TTCCATAGAT GATCGCTCCT FATHER FATHER ATCTAATCAT AAAATAAGCG 18601 AAGTTGCTAG TAAATACGTA AAGAGGGAAC GATTTATTTT AAAATTAACA TGTCATTAAA 18661 ATTATTTT TAATGCGACT GAATTTAAAA TTCCCCCCAG AATATCAATT TTTAGCTTTC 18721 TCAAAAGAAT TTATTTAATG CTTATTTTTA ACTTTAATA AACTTTTTCT AAACAAAACT 18781 AATACTTTTG ATTTATGTTT TAAAAGATTT ATGTAATACT ATTGATGAAG TCTATGTCAA 18841 AAGTATTTTA AAAGGAGTTT TTATCATGAA ACATACGCTT AAAGTTGATC AAGTACGTGA 18901 CGGTTTATGG CTAGATTCAG ATATTACGTA TACGCAAGTT CCTGGATGGC TTGGTAATAC 18961 AACGCGAGAT TTGAAGCTTT CAGTCATTCG GCATTTTCAA ACTAATGATG ATACACGTTA 19021 CCCAGTAATT TTTTGGTTTG CTGGTGGCGG CTGGATGGAT ACTGATCACA ATGTTCATCT 19081 GCCAAATTTG GTTGATTTTG CTCGGCATGG TTATATTGTT GTTGGTGTCG AATATCGTGA 19141 TAGCAATAAA GTTCAGTTTC CTGGGCAATT GGAAGATGCT AAGGCTGCTA TTCGTTATAT 19201 AAGAGCTAAT GCCAAGCGCT TTCAAGCTGA TCCTAATCGG TTTATTGCGA TGGGAGAATC 19261 AGCTGGTGGT CATATGGCAA GTATGTTAGG TGTTACTAAT GGTCTTAACC AATTCGACAA 19321 AGGTGCTAAT TTAGATTACT CCAGTGATGT TCAAGTAGCG GTTCCTTTTT ATGGTGTAGT 19381 TGATCCCTTA ACCGCTAAAA CAGGAAGTGC ATCAAACGAT TTTGATTTTG TTTACCGTAA 19441 CTTGCTTGGC GCTGAACCTG AAGCTGCAAA TCCCCTCACG TATGTAAATT CTACTTCTAC 19501 GCCCTTTCTT ATCTTTCATG GTACGGAGGA TGTCGTTGTT CCAATCAAAG ATAGTGAAAA 19561 GCTTTATGAT GTATTAGTTG AAAACAACGT TCCTACTGAA TTATACGAAA TTGAAGGTGC 19621 AAGTCACATG GATGTAAAAT TCCTTCAACC ACAGGTATTT AAAATTGTGA TGGACTTTTT 19681 AGATAAGTAT TTAACCCGGC CATAGATCAT TTCTTGCCTT TACTACTAAA AAGCAAACTA 19741 ATAACAATCC AACTTTCACA TTATTGACAA AATCAAAAAG CACCATGAAA TTACTTTTTC 19801 ACGGTGCAAC TATTGTTAAT ATTTATCTAC TTGGCTTCCA TCAATGGAGA AATAGACAAC 19861 TTGATTTGCA AACCTAATCC AGCAGCATAT TTATTTAATG TAGGCAGCGT AGGGATTGAA 19921 TCTAAATTCT CGATTTTAGC CAATTGAGGT TGTGTCATAC CGATTTTTTT TGCAAATTCT 19981 GTTTGCGAAA TGCCCTGTTT AATTCTTTGT ACTTCTAAAA AAGACAAGGT ATCAACAATC 20041 GATAATTCTT CTTTTGTTGC AGCCGTCTGA TGCTTATCTA TATCTTCCCA TTTTCTCATT 20101 ATTTACCCTT CCTTTCGTAC CAATCGTCAA GTAGCGACAA GGCTCTTTCT ATCTGACGAG 20161 GATCTGTTTC ATCCTTTTTC TTAGCATAAT GATTTAATAA TACAAAATTA TTTTTCTTCC 20221 ATACTCCATA AAATACTCTT TCTGGCATAG GTCGTAACTC CCATAGTTGA TGCCTATAAC 20281 CCTTTAATTT TTTTGCTTGT GGTGTATGCA ACACAGGACC AAGAGCTTGT AACATCTTAA 20341 TTTGATGGCG CATTTTTAAA TAAATTGCTT TATCTTGCTT TTGTTTACTT TGCGAAATTT 20401 TCTCGAAATA ATCACCAATT TCACTATTTC CATTTTTATC TTCGTAAAAA ACTACTTCAT 20461 ACATGCACTA TTTCCTTTAT TATAGCTTAT TTATTACTAA TTATAGCAAG ATTGCTATAG 20521 CTTTACTACT ATTAAAATAT ATTCCATAAT CAAAAATTTT TCTATTGAAA GCACCCGCAC 20581 ACTCAATTAA ATCAAATAAG TTTACGGCAA TGATTATTTT TGGTGCACAA AAATTGCCGA 20641 TGTTCCCCAG CTTTACAAAC TTTCACCATT TCATACCATT TTAACTAAAC AAAAGCTCCG 20701 GTAAAATGCC GTTATATCAG CATTTTATCG GAGCTTCTTT TTTATACAAT CTTAAAAAAA 20761 TGCGTCCCCC GAGCATAGAA GATTGTTGAT ATATCAACGT TTTGAAGGAG TTAGTGTGCC 20821 AAACGTGTGC GAACTTAACT AAAATAAAAA AGAGCGCCTA TCAGGGCGCC CCACGTTATA 20881 CCGGTACGGA TCAAGTAACG AACTGAATCC AATTTGCGTG CCGATACTTC TCATCTGATA 20941 TTTAAATTAT AACATAATTA TTTTATGATA CAATAATTAA TGCGTGTCGG GAGTAACGAC 21001 CCAAACTATC ACGCAAAAGG GGTGAATTCC CCGTGACATT TATACTTCTC ATTCTGATCG 21061 TGCCGAACGG GCTCGTCAAG CAACTGATGC ATTATGCAAA GGTTGTAATC AAAAAGGCTC 21121 TCAAACATCT AATTGATGAA TTACTTGGTT AATTCTGATA GGAAATGTGC GAGATGCTAT 21181 TTCAGCGGTA GTGTTTGCTA TCGCTGTTTT TTATTATACT TAAGAATAT AGTCATGGTA 21241 TTTTTTTACC TTAGTAACTA TTCAGTTTAA TGTTACTCTA TTAAATTTTG AATTCCTTTTA 21301 CATCCTTAAC CTCTATCATA TTACAATCTT TATCTTCAAC GTAGACGAAT TCTGACATAT 21361 CATCAATATC ATTGAAATCT TTATTAGCTG CGAGTTCTGC AGCATCCTTA AAAAAATTAG 21421 GCCTTTTTTC TTCTATTTTG TCCATCGGTA CTAAACATTT TAATATGTAA GTTTTGAAAT 21481 GCTCTTGTTC CCATCTTGTT TGAAGAGGCC CTTTTAATGG CCTACTTCTA ATATTATCTA 21541 ATTCATATAT GGCACTATCA AGGTACCTTA AAATTTCAGG ACACTTATAA ATGCAAGAAT 21601 AATCAAAATG ATATGGTATA AAAAAGCCAC TAATTCCGTT ATCATTTTCC AAACGTGCTG 21661 CAATATCATT CCAACTTCCA CCAGATTCAA TCAGGTATGA GTGCCCATTA TATGAAATAA 21721 GROUP ATTACK CONNECT CONNECT CLOCK TTCTAAAAAT CONNECT 21781 AGGTACTAGA ATCTGTTATA ACTTTGCTAA GTGGTTTTAA TCCATCATAT AAATAGTTCC 21841 TTTGCTGTGA AGAACAAGTT GTAAAGTGGT AAAAATATGC ATTTTCAATT TCATCTTTTT 21901 TATATAGTTC TAATGATCTT TCAGCCATTT AIDGAGTCGA TAAATCAAAT ATCTTGTATT 21961 TTTTCTTTTC AGACACCATG GTTTTCTCCT TTTTATGATA TATCTAATTT AGATTACTAT 22021 ATGACAAAAC ACCCTAGCAA CCATTAATCG GCTACTAGGG TGTTTATTAC TATAATTTTT 22081 CACTTAAATC TGAATTTGTTT ANSWER AATCATTATT GGATTTGCGA TGCCATTCTT 22141 TTGAGCTAAT GCTTGCCAGG TCTTGCCAAA CTTAGCCGCA ATTCCGCTTA GTGTGTCCCC 22201 TGCTTGGACA GTATAAGCAT TGGATTGTCC GTTGCCGGCT AAGTAGAGTT TTTGCCCAAC 22261 GTAGATCACA TTCGGGTTAG TAATGTGATT ACGGCTTACG AGGTCTGAGA CAGTGGTGCC 22321 GAATTTGGTG GCAATTCCGG ATAACGTATC GCCTGATTGA ACAAAGTAAG TATTTTCGTT 22381 TGATACTTTT CCGGTGACTT TGAGGACTTG GCCGACATTG ATCTGGTTTG GATTACCAAT 22441 ACCATTGATT GCTGCTAGGT TCTGATAAGT AGTCCCGTAT TTTTCTGCAA TTCCACTCAA 22501 TGTATCGCCC GGCTGAACAA TGTAGGTTCC AGTAGCTGGG TGACCAATAT GTTGAACCGG 22561 CTGTGGTGCT GGAATAACAG CTTGCGGAAC ATTGCCTGAT ACTAAACCAG TCGTAAAGGC 22621 ACCGTCAAAG TCATAACTAG TATCAATTCC CATGATGCTA TGATCAGAAT ATTGCCAAGC 22681 ACTTGCATTA TCAATCCCCA GTTCAGTCAC ACCATAGCCA GCAATCCAAA TCTTCCGGGA 22741 ATCAAAGCCA TGTGAATTAA GAATACCGCC AGTGAAGAAG GACTTCATGG AGTAAATCCC 22801 AGTATTCTTG TAACCAAGAG CTTCTACTTC TTGAAGAAAG GCTAAGGATA CTGATTGATA 22861 ATCTGCAGTT GAATGAACTT CCGCATCATC AATCATCAAA GTATCGTCAT ACATACCAAA 22921 TTGCTTAGCG ATTTTAACGA AGAATCGAGC TTCATTTTGT GCATCAGTCA CTGATGTATA 22981 ACGAGCAAAG TGGTAACAGG AAACGCGCAA GCCAACCGCT AAGGCATTAC GAATTTGAGC 23041 GGCCGCACGT GGATTAACAT AAGCCGAACC ATCTTCGGAC CCTTCCGTTA ACTTAACAAC 23101 GACCCCTAAT GCACCCTGAG CTTTAGCAGC TTGGAAAAAG GCAACAGTAT CTGGTTGATA 23161 ACTTGAAACA TCGATGAATT GATTACGCAT ATTATTCTTC CCCTTTCATT GGATCGATTG 23221 CTGGTGCTTG GCCGGCTGGA ATAGTAGCGG GTTTAGTTGG TTGTGATGTC GGATCAACGG 23281 TTGGTGTCAA TGCAGACTTT TCATAAGCTG ATTGCACAAG CGTTTCAATA GCGTTAAGGT 23341 CAATATCTT AATACCCTGC TTTTGAAGTG CTTGTTGAAC AATACCTGTT GCTTGATGAA 23401 ATTTCTCATG ACCAGCCATG TCTTTGCCAA CTAAGGAAGC AACGGCATTA TCTGCAAGTC 23461 GTTCAGCACA AGACCAAGCA GCACGAGAAG TTTCTGTTTT GGCATGAGTG ACTTTAGCGT 23521 GAATAAATGT CTGGCTTTGC TTTAAGGCAA AATAAAAGAC CGTTGAGATA ACGGCCGTCA 23581 TGATATAGGT TGGAATTGCA TTAATGATTG TGCTCATGTT GTTTCTCTTC TTTCTCTACA 23641 TAATCTTTGC TGAGCTTGTA AATATGATTC TTTACCCAAG ATGGTAATGG TAGTCCCATT 23701 TGGCCCCAGT TTTCGATAAT CGAAACTAGG TAAAATAGGA AAAAGAAAAA GACAAGCGAG 23761 TCGCCTGCCT GTCCTAATCC GCATAATTCT AACATTGGAT AAACGGTTAA AGTCAAAATA 23821 ATAACTGCAG CATGTTTCAA AAGTCCACCC GTTCCTTTAC TAGAAGTTGT TCGGTGCGTA 23881 ATGATACTTT TGAAAAACC TGTCACAATA TCAATCACAA TCGCCCAAAC TAACCATTCA 23941 ATGAGCACGT TGTCAATCAT GCTGGCAAAA TATTGAATGT ATAGAACGTG TTGTGGCGGT 24001 TGTGTCAGTA GTAAGTGCAT TTATAGTGGT CACCTCCTTA TAAGGGTAAA ATAAAAACGC 24061 CCTGTAGAGG ACGTTTAAAA TTATTAATT TTTTAAAAA GATTCCCAAT TTCCATCTTC 24121 ATTATTATTG ATTTATTA TTAAGTCGTT AAGTTTATTA TCAATATCAT TAGCTAGCTT 24181 ATACGCACTT GAATCACCTC GTACTCTAGT AATTTCATAT ATTTTTCCTT GACGAAGTTC 24241 TTCAGTCAAA GATTATAT TATCTATTTC GTTAGATAT TTCTGTTTGA GATTCACTTT 24301 ATCCCCATCT CCTTACCGCT AAAATAAAAG TGTTATTA CGCTGTTACT AAATATGGAA 24361 TATTATTATC AGATAACCAT TGAACTGCAT TATTATTATC TTTTACACA TCATCTAAAA 24421 TTATCTAA ATTACKTATA TAACCAAATA TAAAAAATTC ATGCTTATGA GGATCGTATA 24481 CTCTTAAAGT TTCATCTTTT GTAGGAGTGA ACACTTTGTC TCCAACTTTT ATAGTTTGAT 24541 ACAAATTACC ATTACTTTGT TTTTCAACCA TTATGTGCTG ACGTCGGTTA AATTTAATAA 24601 GTCCTTCATC AATATGTTCT AAACTATTCC TGAGGCCTCT TAAATTTTCA TTTTCGACCC 24661 TATTATATA GAAATCATCA GTTACATTCA AAATTTCCCT TACCTTTTTT CGATCATTAC 24721 TATTTTTAGA GTTAGAACCC CATAGAAGCT TAGCTATATC TGACGTATAC AATGCAATAT 24781 TTTGTAAATT ATACCAAATC ATATTATCTT TATAATTT TTCATGTTTG GTATTATATA 24841 TATTTAAT CONNECTIONS GTAAATTAC CONNECTIONS AGTTTCACTA ATTGCATACT 24901 CCTCGTCTTT ACTATTCATA GTATAATGTT GCATAATATT TACCATTCCC CTTATTAATT 24961 GTTTAGTAAT ATTATCGTAT CONTROL AATAATTATG ATTATTAT GAAAAATTGA 25021 AGAAAACCA AAGGCTAATA ATTATTAC AAAAGTATGG AATCAAAATTT TTATAAAAT 25081 GCCGCCCATA ATAAAAGCCC CGCTCGTTTG AGTGAGGCTT ATTTATGTAT TGTGTATTTC 25141 TAAGGCGACT ATAAGTAATT ACCGTTAAGC TAAGAATTCA TTTAATTATT AGCCATTTTC 25201 TTTAGCTTTT CTTTATCTTC AATCTGATAC AAGCGAATCT TAGTAATTAA TCCCTGATAC 25261 GCTTTTACTT CATTGGGAAA ATTATTAGCA GGAGTAAATT TATCATCTTC TTGGGACAAT 25321 TCTATATA NATIONAL TCTATAAA CCTATAAA GTTTATGGTT CASETTCCTA 25381 TATAATTTAT TTTTTTCAAT AATTTTTGeT TCTTTAGGAG TATAACCATC TTGTTTTCGG 25441 TCAAAATAGG CTTCCCATTT AATGCACTGT TCCTGTGAAT TAATCCGATT TGTTTTTAAA 25501 CCAAATGCTG CTAATGGATA CCCACCTAAT TTGGGATTGT TACACAATTC ATTATCATAT 25561 TCGTAAGCAG CHAPTER ATCTTCTAAT GETTTGAAA CHANGE AACCACCTCT 25621 ATTTTAGA GTATCACTAA TTTATTAC WINDOW CTTAAATAAT TTTATTGTCA 25681 TGATTATATGC TCCTTGAATT TCGTAATTCT GACCGGTTAC CGTCTTATAT TCATCTTTAG 25741 TGATCGCTCC GCATCGTACA TAAACTTTGT AGAATTCTAA ATCATGGTTA CCCCAGTCAT 25801 TCCAAAACAT TTGAAGCATT TGTAATTGTG TCATCATTAT GCCGTTACCT CCTTAGATTT 25861 TTCGACTGCC TGTTGCTGAT TAACAGTCAT AAACATTTGT TGTAATTGCT TGATTTGAGT 25921 TGCTTGTTGA GCATTAGTAG CCTGCAATTT TGCATTTGAT TGGTTCTGTT GCATAATCAT 25981 TGCTTGCAAA ATAGTGATTT GTTGATTGGT ATTCCCGTTT GAATGCGAAA TAATCGTCAC 26041 AGGAATTTGA CTATCATTCA TAATAAAGCT CTCCTTAGTA TATTTTTGTT TGATAAAACA 26101 CTGTTACAGT TACCCCTGTA TTTTGTATAG CTGAGTTATC AATGTTTCTA ACGATTAATC 26161 CATCGCCGTT TCCAGCTTCT GAAACACTCA ATTGCCAGCG GTCGCCTTCT GCAACATAGT 26221 TAAGTATTTT CCCAGTAACT CCAAGTTCTT TATTGATAGC ATCCATTGGA AGTGTCTTGA 26281 CCTCTTGCGA ATTAAGTTGA TCAATAGCTA TAAATTTAGT AATCGTCTTT AAATTAGAT 26341 TGTAATCTGT TTGATGATCT TGCAAACTCA TTCCTAGCGA TGTATTGCCT AAACTAATGA 26401 GCGAAGTTGG CGTTTTATCA GCATAAATTC TCCCAGCTTG AAAATGGGCT GAGTTTTGAT 26461 CGTAAAATT AACTCCAGTA TTAAAAGCCTT TTCCACCTAA CTTAAAGTGA TCCACATCTA 26521 GATATGTTCC AGTCGTACTA GGCCCAATAT ATAGCCCATT CATGCTTTCT CTTTCAGCTC 26581 CTAGCATAAT CTCGTTTGCT GTAAACTCAG CGTTAGTTTG CAGAGTGAGC AACTGATCGC 26641 ATTTTCCCCC AAGTGCAAGG TAATCAATGT GGCCCTTTGA TAGCATAATT TTTAGATTAG 26701 CTTGTCCACT TTTATTTGTA ACAAAATGGC TTTCCCAATG TTTGATAGTT AGATCGTAAG 26761 TTGAATCAAT CACTGATCCA ATAGCATTGT CTGCTATATC AAACGTTTCC TCCCACACAA 26821 AAGAATATTC ACCGAAACCG GATTGTTGCG ATACCGAATG CTGATACAAT GTTTGATAGC 26881 AATTATAGTT CCAAAGTTTG ATTTTGATCC CAATATTATG TGTGTTATCT GCATCTGTAC 26941 CAGTTACGTT TAATATACAT CCTCTGAAAT AATACCCTTT AATCGAAATA TTACTATGAA 27001 ACATGGTATC AAAAGAAACC CCATACTTAG CTGCACCTCG CTCTAGCATA ATTTGAATAT 27061 CATTTTGATT TCCATTTCTA AATTTGAATG CAATTTGATC CACGTTTAGT GCTGGTGTTA 27121 ACTTTAACCT CAACGAAATA TGAGACTGCT TCAAGTCAAT AGCTAATGGA CTTTCAATTA 27181 GATAACATCC ATTCCCATGA ACACTTTTAT TATTATCAAC TGCATAGGTT AGAATGCTTT 27241 GAAGGATTTG GTAATCATCA TTTTTACCAT CTCCATGTGC TCCCCATGTT TCAGGTATAA 27301 TTTCATTTTC AATAAGTTCC GCTAATAGTC CTGATGCTAA TTGTTCTGCA TGTTTAGTTG 27361 TTGTATCTGT GACATAAAAA AGCCCTCCTC CTCCATCATT TGGTTCATAA TAGCCAAGAG 27421 TTCTTGCGCA CATATCTTTG CTTAAAGCAC TATCAGCTTT CATGGCAGCT ACATTTGGAT 27481 ACACATGTGC ATAGTTAATC GCAATTGCCT TCATCATTTC CTGCTTAAAC GCCTCTGCTT 27541 CCGCCTGGGT AAACAAATTG TCTTGCTTAA TCTTAGCGTC TAGTGCATCT AAACCATTTT 27601 GAACAGTAAC GCCAAGAGCT TTGAGCGTGT TCATTGATTG GGTAAACTTA TCAATAAAGT 27661 CACTGGTCAT CTTGGTGAGC TTGTCGGTAC TGTCTTGGTA CTTGGCTTCG ATTTCGTTAA 27721 TTAACTCTTC GACGGGTGAA ATATATGTTC GTGGTACCAA GCCATCAATG ACCTTATCAG 27781 CAAGGACATC GAGGTCGAAT TCCAAGGTAG TGATAGAGTT ACCGTCTTTG AGGATGCGAA 27841 AAAAGGCTTG GCGATAGGAA CCAGCGACTG TAAAGGCATG GCCGGGCATG TCGAAACGGA 27901 AACGTCCGGC GGTTGGGTCA AGGGCAACGT AGCCTTTATC ATCAATTACT CGGAAGTCGC 27961 CGGCGGAATT CTTAGGAAGT AATCCTTCAA ACCAGACGTT ACAGCCAGTT AAATCTAGTG 28021 GTGTCCCGTC TTCGTTCTTA ATATTGACAA AAACTTGACG CATACTTCGC TCATACTGAC 28081 GCGCTTGGAC CCAGTTAGTA TTACTGCCAT CAAAGTTAAC CTTGAAGTCT TGTACATTGT 28141 CAACATGCGG ACGCCGGTCT TGACCGATCA CATAAGTTAA AGTTTGTGAC ATTAAATCAT 28201 TCCTTTCTCT TTCAAAATCT GCATGACAGC TTGTTCAACC GTTTCATAGT CGGTCCCTAA 28261 AGCCACATGC TCAATTTTCT TTTTCCACGC TTCTTGAGCC TCTTTTAGTT CATCTCGCGT 28321 GGCTTTTTCT TGTTCGAGTT GGTCGAGACG AGTATTAATC TCCTCGAGTA GCCTAATCAA 28381 TTCTTTATAC TGCCTGTCAC GGAGATTATC GTCTTTGTTA TCCTCATTTT GAATTATCGT 28441 TAAATTATTT ATTAATTGCT GGCGGAATTT TCTTCCACTC TGCAAATCTA GATTAGTTTC 28501 TAAATCCAAA TGACCATCCC CCTCCTCACT TCAAACTACT CCAATCCGTC ACTCTGTAAC 28561 CTAGATTTAC CTGGGCCCGT GATACGTATG CTTTATCAGA TCCGGAAACA TTAAAAACCA 28621 GCCTTCCTTT TAATGTGCCG GCTGGAATTT TAATGTTAAC TGTGCCGGCG GATTGCCAGG 28681 CGCCATTATT GACGATTAT ACAATATTCG ATTTGCCGGC AGAACTACCA TCGCTCTTCA 28741 AGAACTCGAC TAAGTAGTA GCGGAACTTG AATTATCGGT CGCATTTAAC TTAGCCATGA 28801 GACGACTTGA GACGGAG ACACCGTTGA GGTTAAATTC ATTGCTTCTG AGAGTGCCTT 28861 GCTCTACTTC AATTACTGGA CTGTCATTAT ATTTTTCGCT GGAAACAGTT CCGCCAGTCA 28921 TCATAGTTAC CAAATTATGC TGGCCATTTT GCATCCAGTA AATATTCTGG TCTACTGCTT 28981 CCATATTCTT ATCCGTCTCT TTCTTATCAT TCACGACTTG CGTTAATGAC TTGGATTGCT 29041 GATCCATGCT ATTTGCTAAT CCACTAATCC GGAGTCGTTG TTCTTCAAGA GCTTCTTGTA 29101 GACGTTTAGC TTTCTGATTT TGATAATCTA AAATAGTTGT TTTTGAATTA TTTAACGTTA 29161 TTTGATTATC TTGTCCCTTA GCTTCCGGAT ATATCGTATA ACCGACAGTC TTATAACTAC 29221 CTGAATATTT ATCTCGCGCA AGTACTCTTA AAATTTCACC AGCAACAGGT ACAAATGAAT 29281 TTCCCTGAAG CGTGACTTCA ATATTTAAAT CTGGATCAGG TTTAAGAGTA GTTAAGGCAT 29341 ATTTACGCAT TGCATCCGCA TCTTGAAATC TTTCATCAAC AAGATCAGGT CCAGGATGTT 29401 CTCCCCATTC GTCAATTGAC TTTTGATCAA CTACCATAAA CGGTTGAAAA TAATACTCTT 29461 CCTGTGATTC TGTGGTTGTA TCATTTCCGA CAGTATCATT GGTTTCTTTA CCACCGATAC 29521 CATCACGAAT AACTTGTAAG GGATCAAGCC AGGTTCCATC ATTTGACCAG GCACTTTTCA 29581 ATGCAGTCAT TAAATTCTTT TGCTTAGTAA TTCCAATATG AAGATGGCTA GTATCACGGT 29641 GGCCAATAAC ATCCCCCGTC TTAATTTCTT GGCCAACTTG AACAGTAATA TCTCCTCGAT 29701 TCAAAAATGC TTCTTGGTAG CAAATTAAAT AATCATTCGA CACAATAGTT ATATAGTTTT 29761 CCAGTCCAGC AATGTATCCA ATATCCTGGA CTTTCCCACC ATGAATCGCA TGAACATCGC 29821 GTCCAGGATG ATCGACAGAA CCAAAATCAA GGCCATCGTG AAAACCATTA GTTCGCCCCA 29881 CTCCATCTTG AGGGTGTGTT CCAAAAGTTT GCCCCAATGA AAAATGACCT TCTCCAACAT 29941 CTGGGAAAGG CCATCCCCAC GGATTAGGTG GTGAAATGAT CAATTTATCT TTCGTGATTG 30001 GGGCACCATG AGGACTCCAA CCAGTAACAC CATTAATTTG TCCTAGTGCA TTAGGAATAT 30061 TGAAGAACGC AATTAACTGG TCAAAACCCT TTAAGATATT TGTATAGGGC TCCCGACAAT 30121 AAGTATTAAA AGTTCCTCGC TTAAATTGAA GTAACCCAAG CGCCGGACCA GAACCATCGC 30181 CATCGGGATC AGTTCCTGGT TGCGGAATCG TCTCGTTTCC ACCTGATTCC AAATGAATTT 30241 GTGCCCGTAA AACATTAAGC TGCTGAGCAT TCGGTTTTAT TCCATAAAAG CTAGCAGCAT 30301 ACTGAATAAC TGGTGTCCAA TCACCGTTGA CTGGCTCAGT TGGTCCATTA GCATTAGTTC 30361 CACCTGTCCC GGTATAAACA GTGTGCTGAA CCTCATGCTT ACCACCAACA CAACGAATCA 30421 TATTAATAAT TGATTGACTG TCCCGAGTAG TTTTAACTGA CTTTGCATCC CTTGGAAAAT 30481 CAATCACTCG ACCATTATCC TTATAGAACT CATCTTCTGA ATAAACTCGT ATCTTCTTGT 30541 TATCCGGATA TATAACTGCA CTTGGCCATA ACTCAGTAAT CTTACTAAGC ATCTCTTTAC 30601 CACTGCCGCT ATCGAACTTA GAAGTTGACT GCTTATCAAA ATTACCATGA ACTTCATAGC 30661 TAAAGCCTAG CTTATTTCCA TCAATCCAAG CCTTTAGTAA GTCCTCAACT CCATAAGACT 30721 GATCCTTACT AGCATTACTA TCCTGATTGT TATTTAAGGT AAGGTCACTT CGTTTATAAA 30781 TTCGACTAAT CTCATTATAG ACATGCCAAG CAGTGATATT TTTCGTATTA GTATCAAAGT 30841 TTTCAACACA ATTTTTTACA ATATATTCCT GTCCCTCAAG CACAATCGAA CTTTCAACAT 30901 CTAATGGATC ATACAATGCT GAATCGTAAT CAAATACTGA AAAAGTCAAT TGAAAGGTCG 30961 AATTCTTAGA CCACTCGCTT TGCATTGTTG GCCAGAGAAT AATGTCTCCG ATTGGCTCCT 31021 TAGTTGTCTC TTTATGAGGT GTCATCAATA CTAAACTAAT TGTCCTCACC TCCTAACCAA 31081 GATACATAAA TGGGAAACTG AATGTAATTT CCAAATCATC TGCACCAGTA ACTTCAAAGT 31141 CATTCTTTCC AGGCGCTAAA GTAATATACC CATAATCGGT ATTGGCACTG TCTGGGTTAT 31201 TATTCTTAAA TGTTCGCCGT CCCTTTAGCA AGAGAGTATC GTTTCCAGAT AGATTTTGAT 31261 TGTACGTCCA AGAAGTATTA GTAGTTGTAT TCTTTACTGT GAATTTTCCA CCATTATGCT 31321 TAATAGTAAT TTTTAGATCA TGACGCTGTT CAACAGGATC GATTGTAATA TCACTATCGT 31381 TAAGGATAGA AAACTTATTC TGGCCTTTGA AATGGTATGA AGGAGTTTCC TCATCCATGT 31441 TCATATTCAA GTCTAAAA TCCTCATCTT TCATCTCATC CGTATGCAAT TTACTAAATC 31501 GCATTCCGCT TGGATTTTCA AAAGGCACTT CAAACGTACA ATAGTTAACT TCTTCTGGTT 31561 CGCTTTTAAT CTCAAAGGAA CTAGCCCGAC AGTAACGGAC AATATCCGGC TCAACTCCTG 31621 TTCTTAACCT AAAGATTCCT TTTTGTGCAA AAACGCGATA AATCTCATGC TTTGCCATCT 31681 TAAAATCTTT TCGATCAAAG AACTGCAATA AGAACTTAGC GGTGATCGTC GTTTGGCCAT 31741 AACGGGAATA ACTCCAAATT TGACCATCTT GTTGGGAATC ATCACGATAA TTATTAATAA 31801 CACTAGGCGA TTCAGTTAAG CCAAGAAAAG TTAAGTGGTC AGTAATATCT GTGCTGGCCA 31861 CTTCTTTTTG ATCATCAATT TTAATGTAAA GAATGTTTAC AGCGATTACG ACCACCTCCTT 31921 AAAGATGTTG ATTATCAAAT AATGCTTGAT CAGTTCCTTC AATCCCATAA AACTGGTTCT 31981 TGTCAAAGGC GCCGGCTTTA ATTGCAGAAA GTTGAGCTGC ATTTAAGCCC AGCATTGTCC 32041 CAAAGCGGTT GAGCATCTGG TCCATCCGAT CTAACATCTC TTTTTGCATT CCATTATTAC 32101 TTTGGCCACC GTTATTATAA TTATTTACAA CTTGGGTGCT TTGCATATTG GGCTTAAAGT 32161 TAGTTAATAC CGAAACAGCA TCATCAGTAC CATTAGCATA TTGTGGTAAG TGCTTAAACA 32221 TCTTAGCAGT ATCGCTAGCT TTAACAACTT TTGTTCCTCG TGGTGCTGGA AAGACTACAT 32281 TACGCCCATA AGGAATAAAT GGTGTTTCAC CTGGGAATTG AACTAACTCA CGAAAGACGG 32341 GGCCAGGTTG ATCATTAACT TCCATCAATC CACCTTTATG GTAATTAGTT CCCTGAGCAT 32401 GCTTTGATTT ATGAAAAATA ACATTAACTG TTTTCTCAAT AGTATTAGGT ATACTCATAA 32461 AATTATGGAT TGCATCAAGT GCTGTTTTAA TTGGCCCAGA AGCTTTATCA TTAGCTTTTG 32521 CAATTTTTGC TGGTCCCGTA TTTGATCCAG CAAAAGCATT TACACCATTG CGAGCACTAT 32581 ACATTGGTCC ACTAGCATTA TCAACGGCTA AAGCATTTTT AGGAGCGCCA GGATTTGAAC 32641 TAGCAAAAAC ATCGACACCA CCAGTAGCAT TTCTCATCGG ACCACTAGCA TTGTCAATTG 32701 CCAGTGCATT CTTTGGTTCT CCCGGATTAG CATGACGCCA AGATTGAAGG GCATCGTTAG 32761 CAGCTTTTAG ATTTCCACTA GCTTTATCAT CAGCAATGAT TTGTTTTGCA GCACTAACCG 32821 GCATCCCCTT CCACAGCCCA TAATCAGTGA TCAGTTGCTG TAGTTCGGGT CCACCCTTAG 32881 CATTTACGAT TGCTTGCTGT TGCTTAGGAC TAAGTTGATT CCAGCGACCA ATTTTATTGA 32941 GCGCATCCAT TAATCGACCA GCACCCTGAG TAGTAACCAA AGCACGTTGT TGCTTAAACG 33001 AAAAGACTATT CCAAACACCA GCCTGCACTA ATGCATCAAC TAATTGTGGA GTTCCTTTAG 33061 CGTCAATAAT CGCTTCCTGT TGTTTTAAGG TTAAATTATT CCACTGTCCG GAACTTTGCA 33121 AGGCTTCATA AATTGGCTTA GTTGCCTTAT TAGTAATTAC TGCTTCCTGT TGTTTTAATG 33181 ACAAGGAATT CCATGCACCG GATTCAAGCA GAATGTCGGC CATTTCTTGC TTACCTTTAG 33241 CCTTAACAAT TGCTTCTTTG GTCTTAAGAT CAAGATTATT CCATTCTCCC GACTTCTCTA 33301 AAGCTTGAAC AATTGTTTCA CTAAAGCCGT CTTTCAACCA AGCTTTCTGC TCTTTCCAAC 33361 TCATGCTATC CCATTTACCA TTTCGATTA ATGCAGCTGC CACCATTTGT TGAGCATTGG 33421 TACTTAACTT ACCTTCCTTT TTCATTAT TAATTTGGTT CCATTGATCT TTAGATTAA 33481 CAGCCTTATT AACTTCCTCC TGGGCATTAG TCCGAACTTT ACCAGTTTTG GGATCGAAAA 33541 CTAAGTCATT CCACATATCA GCGGCTTTTT TAGCTTTTCC ACTTAATTTA GTAGTATTTA 33601 CCGCTAAGCT TTGTAGGTTT GTTTCGGCAG CTTTGGATTG CCGCTTAATC TCATCAGTGC 33661 CATCTTTATA ACTAAGTCCC ATACTTTTTA GGTCATTCTT AATTAATTTA GTACTTTCAC 33721 CATTAGCACG GGCCAGGCGA ATATATTCGG CAGCTGCTTT ATTCGTGTAA TCTGTTAATG 33781 CTTTCTTATT AGCACGCATA CCGACCTTAT ACAGTTCAGA ATCTTTTCCG TAGCGTTTAG 33841 CAAGCATTGA AGACTGCTTC TTGTATTGGT TTTCCATTTC AGCAGTTTCA CTGGTTATAT 33901 CTCCCATTTT TGTTGAGCGT TGTTGCATAG ACATATGCTT AATATCGTTA TTAAGGACAG 33961 CCATTGCTTT AGCACGCTTA CTTCCACTTA ATTTAAGAAT TTTCATCTCA TCGTTAAGCA 34021 TTTCCTGCTG GTTGTTCTTT AACATGACTC GCTGAGTATC ATTTAATTGT GAAACTTTTT 34081 TATTGTGGTC AGATAGAATT GTTTGAACAC GCTGATTGGC ATTATCTGCA TCATTCACAT 34141 ATGAATTATA TTGTTTTTTC TCCTTTTCTA ACTCATCGTC AATAGCTTTA GATATTTCTG 34201 GAGACAGACC TTTTTCTGCC TTTTTGGCAT TAGCAAAATG TTGTTTTGCA CTATTTTCAA 34261 TATTAGTAAA CTCACGGTCA AAATCAGCAG CTAATTTCTT TGTTGAAGTT GAGGCAGCAA 34321 CATCCATATC TGACAGAGTG TTCTGAATTC CTTGAGAAGT CGACTGCATT TTTGATAAAG 34381 CCTTATCAGC AGCTGCACCA ACATCAGATC CCCAACGATT CGTTCGTTGT GATGATTCGA 34441 CAGCTTTCTT ACCCCAAAGC TCCCAAACAG TAATTCCACC GGCAATGGCT AAAGTAGCAA 34501 CTCCAGCAAC AGCGGCAACT GTTCCTAAAG ATACTCCAGC CGCAGCAGTA GCAGCACCTG 34561 CTTCACCTGC AGCTACACCG GTACCTTGTA AAGCGACAGT CGCAGCACCA ACACCGTTAG 34621 CAGCTTGAAC CGCCCGACCA CCTGCACCAG TCATGGTTGT TCCAAACTTT GCAGCTTGAA 34681 ATGTTGATTT TGAAAAAGCT GAGCCAATAA CGTCTAACCC ACTGGCTCCT AGTTTCATTG 34741 CAGTTTGTAC ACGGCCGATT CCGGAAGCAA TTTTTCCAAA GGCAAGAACT GTCTTCCCAG 34801 CACCACTAGT CAGTTTACCC AATGCTAGGA ACAACGGGCC TGCACCAGCA GTGAACAGGG 34861 TAGTTGTTAC AATTGCCTTC TGGACAGCTG GTGATAAATC ACCAAAGCCA TGTGCAAGTC 34921 TGGAAAGGCC TTGAACCATT GGAATAATAG ATGGTAAGAC GTACTTTGCC ATATCCATTC 34981 CAGCGTTAGT TAAAGATTCC TTGAAGATTG CTAATTGTGC TTTAGGAGAT TGAAGGTTTT 35041 TCTGTGACAA GTCGCCGATA TAATCCCGCT TGGCAGAGTT TTGAACTTCT TTATTAAGTT 35101 CACGTAACCG ATTAGCGTTT TCGGTTAAAA TTGCCCCAGC TTGTTGTCCA GTTGTTCCAA 35161 ATAACGCATG AAAAATATCA TTCTTTTGGT GACCAGATAA GCCTTTCATA TGGTCATTTA 35221 ACGTCTTAAA AATAGACGAC ATTGATTTTA ACTTTCCACT CTTAGTAAGA AAATCTTTAG 35281 TACTTAAATT AATACTTGCT AAAGCTTTTT GACCATTAGC GGTTGGCGTA ATTAGTGAAT 35341 TGATAACCTT TCGTAGACCG GTACCAGCTT TGTCTGCTTC TAGACCATTA TTAGACAAGA 35401 TCCCCATTGC ACTAGCAGTT TCTGAGAGAC TAAAACCTGC TTGATGAGCA GTTGAGCCAA 35461 CATATGACAT TCCCACACCA AGTGATTGAA AATCAGTTGA TGTGGCATCG GCAGCATAGG 35521 CTAACTCATT TAATGTTTTA GTAGATCTAC GCTGCATGAC TGTAGCATTC TTGATTGGAC 35581 GTCCTGCTTT ATCAGTAGCC AGTCCAAAAG ATTCCATTGT CTGCGAAGCA ACTTTGATTA 35641 CATCATTAAA GTCATCCCCA GTGGCCACAG ATGCTTTAAG TTCGTTCCGC ATTACTCCAA 35701 TTGCTGCTTT AGATGTATAA CCACGCTTTA CTAGATCTTG ATACCCGGCA GCAATCTTTT 35761 GCTGACTAAC ACCGTACTCG TCAGAATACT TTCGGGCATC TGCAGTCATC GTTTTATATG 35821 CGGCATTCGT TTCTGCAGCT GATTCTCCGG AAGTTCGAAT AACGTTCTTG ACCTTTGTCA 35881 TTTGATCTTG GAAGTCAACG AGTTTCTTAG CGGAATATGT TAACCCTGCC GCAATTGGAG 35941 CTGTTAAATA AGTCGACATC CCTCGACCGA CACCTGATAT TTTAGAACCA ACATTGGTGG 36001 CCACATTTCC AAAATGTTGA GTGCGATTAG CAAGTTGTGT CCACTTATTC GACTGCAATT 36061 CAATATCACG ATTAAGAGCT TGCATTCGTC CACGTAATTG TTCAATTTGC GCAGACGTTT 36121 TATTATATTG GGTTGCTGCC TTAGTTCGTG ACTGCTCGCT CCTGGTAGTA TCATCCATTG 36181 CTTTCTTAGC ATTCTGGAGT TGCGCATTAT AATTGCGCAT TTGTTGACTC ATAGTCGCAT 36241 AAGCAGCACG RECORD ATACTTCCAC CGGATGCTTT CAGTGCCGCT TCTTGCGCAC 36301 GCAAAGCATT GGCTGTTGAT TTAATTTGCG CTTTTAAAAC ACCATTAGCC GCTTTAAACG 36361 GATCAATATC CAAACTAACA GTTGCTGCCA AATGTCCTAA TGATTGGGTC ATTATTTAAC 36421 CTCCTTTCCT AGAATAAGAA TGGGAATGCT TTATCAATGG TTGTCTGCTT TTCTTCAAAG 36481 ACGTAATTCA TTAATTTCAA ATCTGAAAGT GTTAGCTTAC TGACCTCATT CCATTTATAT 36541 CCATCGCGCA TTTTATTTTT AATGAAATCT GTGAGACTCT TGATTGAATC ATCAATCATC 36601 TCAACAGTTA TTTTTTTGGC TTTTCGTTAT CCTTTTTCTC TTCTAAGTCA TCTTCACTTA 36661 GAGGAGAACC GAGAGTTTCA TTAATTGCAT TAACAATGCT AATTAACCCT TCTATAGCCG 36721 TAACTCCTGA AAGAACATCC TTTTTAGTCA ATCCATTCTT CCAAAAATTA GCAGCAAACT 36781 CAGCCCGTAA ACTTAATAAT CGTTCATTAT CTTTATCTGT TGGCAATTTT TTGGGATCAG 36841 AGTACATCAC TATTTCTTGA CGTTGAACCT TTAATGCATC TAATAGATTT TCAAGCATTG 36901 GGGCTTCTTT TCGTTCATAG ATTGTTTCTT TGCCATCTGT TTTTACTTTT AATTTATATG 36961 GCATTTCCAT ATCCTCCTCA TCGTCTCACT TAACTCGTCT CTGTCTGATT AATTAGTTAC 37021 CCTTTATCAA CAACAGTTTC TGGTTTAGTA TCTTTTGTAT TGGTTGGATC AGTTACTGGA 37081 GCTTCTTCCC CAAAGACCAT TGCATGGAAC TTAGCAAAAT CAAATCCTTC ATTATCTTCC 37141 CGACCGATTA AAAGGATGGT TCCAGTATCC GCATCCCCAC GCGGAACGAA ATTACCTTCA 37201 ATTTCATCTG CTTCTGGGTC TGGAGCACCG TCCTGAGTCT TGATTGAAAT ACCTGGTAAG 37261 GAGAACATCC CCTTGGTTAA ACCAACCCAA CAATGCTTCC CGTTTGAAAG CTTTGTCCGG 37321 AACATAGTAG CAACATAATT TGGTACAAGA TTCTTAGTAT AAACTTCTGT ACCGTTCTGA 37381 ATATCAATTC CATACAAGTC TTTCTTCATG ATGGAATCAA TATCATAAAG GTTGATGGTT 37441 TCCTTAGCTT CGGTAATTCC ACCAGAAAGA ACCAAGTAAG GGCCGTCATC GGCTGCTAAC 37501 GTCTTTAATT CGTTAGTCAG CTCCAGCTTA ACTTCACTTA ACCCGCTCAT CTTTCGGGTA 37561 TCTTTAATCT TTTCGTTCTC GTCTAGCACC CCATATTCAA AATTAGAGGC CCCAAACTTA 37621 GCAACTTTTG CATTTGGTGT TCCCATTAAA TATCATTCCT TTCTTCAAAC CCTTCAAAGT 37681 TAGCTGTGAC CATTATGCAA TTATCCAAGT CCGGATCCGG ATAAGAATTC TTGTAGTAAC 37741 GTTCAAAGCC ATGACTGTGG AGGGTTTCAT ATATTCGTTC TTGAATATCC ATTAGCCGGT 37801 CATCATTCTC TTCACGAATC CAAAAATCAA CTTGTACACG TGGGTATTCA AAAAAGCGAG 37861 CATTGTCACT GTAAATTGCA TCATCCCCAG GTAGGGGGGT GATCCGAATC CACGGTGCTG 37921 AACTCGCTTT AATAAATGGA TCATCAGGCG TACTAGTAAA AATTGGAACA TATGATAATT 37981 TATCTTGTCG CAACTCATCC ATCATCACGA CTAGGCACTC ATCATTCGTT AGATAATCGG 38041 CTACTTGCAT CTCTGGAGTT TTCATACTTT CAAGTCCTCA ATAAATTTAG CCAATATTTT 38101 CTTCTTAGCA GCATTTCTTG AATCTTCAAC AAAGTGTTGT GGATCTTGCT TAGCAGTTCC 38161 AGCATCGGGG AAGTGAGCAA TCCATCCTTT ATCTTTGTCA TAACCAACAT CGACAGAATA 38221 ATCTCCACCG TTAGTCTTGA GATTACCGTG TTTAGTATGA TCTTTTAAAG GAGTCTTGCC 38281 TGAATGATCA GAGCCTTTAG AAGCCACAGG CGTCCATTTT CTTAATTCTT CTTGAAAGAC 38341 TTTAGCACCA TCACGGGTTG CTTTTCGTGC CTTCTTTTCT TCCGTCTTTT CAAGTTTAGT 38401 TAAGTTAGCA ATCAGCTCTG CTTCACCGGT CACTGCCATT TTGGACAACC TCCTGGGCGG 38461 TAATTTTTGT TAGATCTCGC TTTGCATAAT CAGGATCCAT TCCCGTGATT TCATACCATT 38521 TTCCTCGCCA GTTAATTAAC CAATTCGATT GAATTTCCTT ACGAGTTTTG AAAGCAATTA 38581 AAAACGTGGG TGATTCTTTT CTGAACCCCA CGTTTGAACT GTTTTGGACA AATTCACGGA 38641 CTGACAGCTT AGGAACTTCT GCCCACACGG TAAATTCCTT AACTTTCTGA TCCTTGATCG 38701 GTCGATGAGT TTCCGGATTG ATCCCCATTT GGACTGAGTA AAATGTTATC CGTTCCGTCA 38761 TGTTCCGTAG TTTCATCGGT ATTCACCTCA CTACTTATTT GATTAATAAG GCCATCAATT 38821 CCTGATGAAA GAACTGGTCG GTAACTATCT GCAGTAATTC CTCGCTCGTA GAAGTCTTCT 38881 TTCACCTGCT TCATAAGTGC AATTTTGAAT CGCGGTTCGT CAGAGTAGTC AGCAGGCTTA 38941 CTCTCCCATT TAATTGCCCT TGCAATCATC AATGCGGCAG CATCAACAAT TATTTTAAGA 39001 ATTTCATCAT CAAAGTCCTG GTCAATTTTG CAGTAGTTTT TTAGATTGGC AAAGAATTGT 39061 TCATCACTCG AGAAAGTGTG GTCTGTTTCC ATCCTACTCA CCTAGCTTTG CTAACAGTTG 39121 ATCCTTAGTA TCGGTTGAAG TATAGGCAAT TCCATGATCA TCTAAGTACT TTTTGATTGT 39181 GTCTACCGTA TCAGCACTAG TCGGTTTAAC GTCCGCCCCG TTGTCGGACG GCGTTATTTT 39241 GACGCTGCTG ATGGACCAGT AACAAAGTAA CCAGCGTTTT CATCGGCCTT CTTCACATCT 39301 AAACGAAGAA CCGCTTGGAG ATATTGACCA TAAATGTCAT TATCAACCCA CCGTACCTGG 39361 AGATCTTTTC GATTTGCTAA AATAATTGCA CGGTATGGAT CACCAACAAA GGCATGAGCT 39421 TCACCCTTTG CTCCAAATAA GTCATCTTCA ATTACAGCAA CGTTGATTCC AGAGACCGCT 39481 TTACCAGACG GACTAGAAAT ACTATCTTGA AGTAAGTAAC GTCCATTCTT ATCTTTCAAT 39541 GTATCAAGCC AGTTGTAGAA GCTTTGGCTG GCAATAATCA TCTTATTGTA AGCCACATCT 39601 AAATCGACAT TCCAAATTTT CTTTAGGTCA TCGATTGCAT TAGAGCCATC AACGGTCTTA 39661 GCTGAAAATC CCTTAAAAAT TGTAGCAATA GCCGCATTCT TTGTATTTAA GGATTGTTCT 39721 TTTGCGTTTC GAGCAACTAA TCCAGTTAAA TCAATTGCTG AATCATCAAT CGATTCTTGT 39781 GAAATAGGAA TTGCTCCACG ATAGGTCTCA ATTTGCCATG CTACCTTAAG AAATTCAGGT 39841 TTTTGAAGAT CAGGATTCTT TGCAAGTTCT TCAACAGTAT GCATTTGAGC AGTTGCCTTT 39901 TTAAGAATTG GATAACTACC AGAAGCAGTT GTGGCGTTAA ATACTTGAAC AAATTGGCTA 39961 AGATCAGTTA CTGTTTTAAT TTCATTTTCA GGATTGTAAA TGATTGATTC AGGAATAGTA 40021 ACGCTTGCGT CTGAAGAAGT AATTCCAGTA GTACCATCAC GATGTTCTTG GTGAAGATAT 40081 GCGTTGAAAT TACGTTTTTC TTCATTTTCG TCCTCGTTAT TTTGAGAACG CTTATGAGGA 40141 TCTGGAGCTG GATTACCCTT AGCTGCTTTA CGGTAAAGCT TAAGGTCATC TTCAATACTC 40201 CGAACTTCCT TTTCAGCAGC TTCAATTTCA GAACGTAATG ACTTAGCTCG TGTTAAGTCT 40261 TCATCAGTTG CGTCTTCATT TGAGAGCAGT TGGCGCATTT CATTAGTTTT TTCGTTAATT 40321 AATGCTCGCT TACCTTCTTT TTGAGCAAGC AATTCTTTAA TTTTTTCGCG AAACATTTAA 40381 TTTCCTCCTT CGAGTGTCTT CAATAATTCT TGTCGTTCTA ATTCACGTAA CATCTTTTTA 40441 CGTTTCTGAT CAGTAGCATC TCTATTTTCT TGGCTCTGCA TTTGCTTAAC CATATTGATC 40501 GAACGCTGAC CGACCTGAAC TTCTGTATCC GGATAAGCAG GTGTTGTAAC TACTGATACA 40561 TCGAACAAAC GATCAATTTG TCGAATGGTT CGTTCATAAT CAACTCCATC CTGGTCAGAT 40621 TCTTCCCAAT CTTGGGCCTC ATCTGTGTTG GCCACCGTAA AAGCAAAGCT GCATTGATTA 40681 ATAACGCCTG CCTTGATATT GGCGATCAAA TCACGCGCAA ATGATGTATC AGTTGGCTTA 40741 ACAGTGAATT TCAAGCCAAT TGCATCAGAA GATAAAGTCA TGTTCACCCC TGATCGTCCC 40801 AGTACCTGGT TAGGATCGTG ATTGATCGTC GCTACTACAT TTGACATATC AGCGTCATCG 40861 AACGCTCCTG GAGCAATTTG CTCAATAAAG CGAGTAAAGC CACCCAAAAC TTCGGATGGC 40921 TTATTGTATT TGGCTGCATA ACCTTCAATT ACTGGTTCAT CATCTTCATC AGTTGCCGTT 40981 CTCATCTGAA TTGGCATCAT TAACTGTCGA GTTTCCAAGT CGCTTGTCAT CGATTCCACC 41041 TCCCTTCGCT GTTGATTGTT TCTGATACTC TTCTTTTTTA TCAAGGAAGA CAGTATTCAA 41101 GGTTGATTGG AAACGGTCTA AGTCTGGATT GTCAGATTTG ACTAACCCCA TCCGAACTCG 41161 TCCTTCATTA GGAGTAATGA CGTTATTTGT AACTCCCTTT TGTACATCGT CCATTGACAT 41221 CCCTGTTTCT TTGCGTGTAT CAAATTCGAT GTGGCAGTTA TGACGTTGCC GATCAGTCAG 41281 CATTGTCATT TCCAAATTAC TTGCAATCGG CTTGAAGTAA TAAGGTAAAT CAGAAGTAAT 41341 AAAGTCTTCA TTTAATTGTT TAATCGATTG GTTAGGACTA TTAACTGCTA ATTTATATGC 41401 TGGAATATGC AACGCTTTGG CAATTTGAGC AGTTGAATAG TTGTTGCTGT TAATAGTTG 41461 CAAAACATTG GTATCAATCT CAATTGGCGA GTAATCGAAT GTATCATCAG TAACGATTGG 41521 GCTACCGGCA TTGCTATTAG CTTGTGCATA TTCAAACGCC TTTCTAGTTT TAAGACGCGC 41581 TTCCGGACTT AACTTACCTT TAGCCTTTAG TAATCCACCT TTAAGACCTG ACTTAAAGAA 41641 CCGCCGTAAA GTCTTAATTC CATCATCCTG TAATCCAATC TCATCAGCCA AAGACAACAA 41701 CGGCGACCGG CCATGAATAC CATCGTAGGT AAAGACATA AAATGAATTA CATCTTCAGC 41761 CGGCACAACG ATTGTTTGAC CACCGCCTTT TTGATTGATA GGTGTAAATT CGTATTTAAT 41821 ATTCGTTACA TCAGAATCAT CAATATAGGT TTGCGATGGT GGAAAATATT GTATTTCTAA 41881 CGGTGCTTTT GTATGAGGAT CACGAATTAT TCTTGAAAAA CCATCCCCAG TTAAAATTGC 41941 GTTAACTGTC ATTAGGAAAC GCCAATGATA ATTAGTAAC ATATCGTTTG GGTGCTTATT 42001 CAGCAAATAA TCAACACTTT TGATATTCTT TACTGCATTT TTACCATCAT CCAAAATGAC 42061 AATCGGAAAT CGAGCTACAT TACTAGCAAC ATGAGAGACT GCAGTCAGCA CATCAGAGTT 42121 TCTAAGAGCA CCGATTCCAC TATAAGATGG CATATTGCTA AACCCCGGAA GAATCCCCTG 42181 GTCAATATAA TCTTGTGCCC ATTCGCGTTT CTCGGTATGA AATAACACTC AGCTTCACCC 42241 CCTTTCAATT CONTACTAG CATTCAATT CAPTAIN GTACCATAA 42301 CTTCGTGGAA AATAAAAAGC CTGTAACTGC TAAACAGATA CAPACITY TGAACAGCAA 42361 AACCGGTTCG TTTAGTTTCC AGAATTCAT GGCATCACCC GGAGAAGAAA TTTCAAGTCT 42421 TCATCCGTAA TCTCAAATTT CTCAATATAC GGGGCAAGCT TTCTCAGTCG TTCCAATCGT 42481 CCCTTGATTT CATTAAGTGC GGGAGTTACA TCAATCTTCA TTCCTTCTTC ACCGTCGTAT 42541 AGATACTTAG CCATGTCTAT TCCTCCTCGA TTCCTTTGAT AAATTCAATT GCTTCCTTAG 42601 TTAAGGCCAA TGGATGGAAA TATTCTCCAT CTGAACAGTC ATTGATGATC TTCCCTTTTA 42661 ATAGGTGCTC CACATCATTT TTAGTGATAA AGGTGGTCCA GTTGCTATCG TTGCCATATT 42721 CATCTAGTTG CTTAATATCA TGGCTAAATT TATCTTTTTC AGAAACCAAA GTCATCATTA 42781 AACACATCCT CATCTGTTAA ATAATCATCA ATATTTTCAC GGAAACAAAT TGCATATGCG 42841 TCTAGCAATG CATCGGCAGC ATCAATCTTA TTTGAATAAC GGTTCTTATC AATCCGGACA 42901 CCATTGTTAT CTGATTTAAG GATCGCGTTA GCCATTGCGC CAGTTAAAAT TTCATTGTCA 42961 GAATGTCGAA CTCGCTTATC TAAAATATCA TCCCTAAATT GCTTGGTTGG CATTGAAAGA 43021 GTTAGTGTTC CTTGACGAAC AGATATCTGT TGCCATTCCG GATGACCTTT TTCAATCTGA 43081 GTTAACAAGG TTCCATATTG TGCGGGGTCA TAACAAATTG CCTGAACATC AAGATTGTGT 43141 TCTCTGACAA AGCCATCCAG CCATTCATAT ACCCGTTCAA CATCAATAAC TCCAGATTCA 43201 AGCTTCGTAA TTTCACACTG GCCCATCCCT TGCAACCGGA CATAATCTAA CCGGTCTGCT 43261 TTAATCTTTG CTTCCAAACC ATTATTAGTA CCGACAAACG CATAAGAATC CGCATACCAA 43321 TACCCCTCTT ACCAACGTCA GCATAAAGGT ACCAACGTCA 43381 ATCCCAAACC AAACTCGTTG ACCATCAATG TCAATTGGAT CAATTTGAGC TGCATTCCAA 43441 GTATCAATAT CCATATAACT ATCCTCTTCG GCTTGTCGCC ACATTAAACT GTTCTTAACT 43501 AGAACAGA TCTTTGTCCC TTTCTGTTTA GCTTCTTTCC ACCGCTTTGC CAAATATCCA 43561 TATACCTGGT CTTGCAAAGC CGGGACACTC AGAATTGGAT TGGATTTAAT CCAGGTACTT 43621 TTATCATCAA CTTCTGATAC ATTATCTTGT TCAGCAATGT AGGCAAATA AGTATCATCA 43681 GTAATTTCAC CTTTCAAAAC CTTCGTTGCA TAGGATTT CAATTGTATG CATTGGAACA 43741 TTCAAATCAA AGCCGGCTGT TGAAATAATC ATGATAAGTG AGTTGAAG TAAGGCCTGA 43801 CCGGATTCTA GTAATTCCAT CATTTCAGTG GTCTTACTTG CAGCATACTC GTCTAGGATT 43861 CCAACATGAG GTTCAAAACC ATCAACCGTT CCCGTTTCCT TGGAAAGAGA CCGAACATAA 43921 GAATAATCAT CAAGGTTACT AATTAAATCA CGATTAACTT TTGTCCCACG TTTTGTATCA 43981 CCATCACTGG AACGTAGAGC ATTGAGGCGT TTCTTAATCA TATTAAAAAC GATGTTCGCT 44041 TGCTTTTTAT CGTTAGCGGT ACAAAATATT TGCCGGGAGA ATTCAGGTGA GTTACCCATC 44101 AAGAACTCAT ACAATGCAAT TCCGGAAATA AGGATCGACT TACCATTTTT TCGTGCCATT 44161 GATAACATTC CTTTTCGGAA GCGCCGTTCA GATGGCTTGT CTTTTTTCCA CCAGCCATAC 44221 ATATTAGCAA TAATGAAACG CTGAAAATCT GCTAAAGGAT ACGCCCGCAT CGTTTTTGGA 44281 TCCGGAAGTA TTTCCATGAA TTGAATAACC TTATTAGCAC GTTCATTATC ATAAAAATAT 44341 TCAAAGTCAT CGTTATCCGC CTTTTTAAGA TCATTTAAGT ACCTTTTTGC AGCTAAAATC 44401 ACCTTTTTAC CAGCAACTAT TTTGCCGGCC ACGACCTTTT CAGCATAATC TTTAGCGTAA 44461 TTCATCATGA AATCCTAAAC TTATCACGCA AGGATTGATG CTCTTCCTTG TCAGTTTGTG 44521 GCATGTTCAT CTGCAGCCGC GAATTAACAT TAAGCCCAAG ATCAGATGCA AGACCCTTTA 44581 TTGCCCTGGT TGCTTTATCA ATTGTCTTAA TTGCGTTATT GATTTTAGCA ATGTTCTTTC 44641 TTTTCTTGGA CTGTTCCTTA TTTAATTGAA CGGAAGCATC TTTATAAATG CTGTACCAGG 44701 TACAATACAA TTCCAATTCG CTCCGGTCCA AGTTACGCAA TGGCAGCTTT CCGATAGAAC 44761 CAATAATTCG CCGATATTCC GCTTTGGCCA CCTTATCTAA ATGTGCCGGC GGAGTCTTTT 44821 GCAACTCAGG TAAACCATCG GCAGCCATAA ATTCTGCCTT ATATTTTGCT TCTTGTTCAA 44881 CCACTCTAG GTGGCCTGTT GACTGCGATA ATAATTTTTG CTTTCTTGCC AA (SEQ ID NO: 11). Bacteriophage locus 3 has the following sequence: 1 CTATACAAGC GCCCGCAATT GTTGAATCAT GCTTAACACT TGGTAAGGGG TATTTGACAT 61 GTCAATACCT CTATTTTGAT ACCAAAATTG CGCCAACATC TGAACAGCGA ACGTATATTG 121 TTCATACTGG GTTAAGTCTG CTGTGGGGTT TACAGCGTTT TGTACATAAG CCTTAGCGTT 181 CTTTAGATAA TCCTTGATTA ATTGGTCTTC TTCTTCACCG TCAAGATATA AGGCTTGCTT 241 AAAGTTGTCT ACTTCCCACT GCTCTACATC AAATTTCATT AATTTCACCT TCTTTTAGAA 301 CACATCTAGG TCTAACTTTT TAGCAACATC TACTATAAAT TGATCACGTA ACTTGTACGC 361 TTTTGTAGTG CTACACCATA TATCGCCAGT TGCTACTAGG TTCTTTATCG TCTTATGATT 421 AGGGTTAAAA TAGCATTCTT TAATTATCTT CTGGGTACAG TCCCCAGCGT CTTGTAATGC 481 TAAGTCAATA GCTTCTTTCT CACGTTTTAA GCGGTGCATA TATCTATCTT GGTCAATGGT 541 TATTAACATA TCATCGTAAT AAGTCCATGG TCGATTGATA GCACGTCCAC CACCTACATT 601 TTCATCTCTT TTGCGGATAG GGTGCATTAG TTCAAACTTA CGGCTTTTTA GTTTCTTATT 661 AATTGAAGGA TAATCTTTCA GTATTACTAT TACTAGACTT TTTACTTCTT TTCGCATTAA 721 TACACCTCAT AAAAAAAGAG TGGGCGATAT TGCCCACCCT GTGCTAGTAG CTATTATTTA 781 CTTTCGGTCG CCTTAGTTGT GGTTAAAGAG AGATTAAAAG CAGCGTCATT ACTAATTGGT 841 TGGTAGTCAT TACGGACGAT AACAGATAAA CCTTGACTGT AACTGTCGAA CTTGTCCCAT 901 TGGGCTGTAA CTTGATTACG CCGGAATACT GCTACCGCTT CTGAAATATC ACCTAAAATC 961 ATTGGATGTG AACCGTCTGT GTTATCTGGT AAGAACTTAT TACTAATCTT AACAACGGGT 1021 TGGCCAAGTA AAGAAAATCC ACTAGGAGCG GTTACATCTG GTTGTAATAA GTAACGTCCT 1081 TCATTGTCTT TCAAAGTATC TAATACTTGG AAAGCTGATT GATTTACTAA CCATGTAGAA 1141 GTACTTTGTA AGGCTGGGTC AAGGTCAACG TTGAATACTT GCTTCAAGTC GTCAACATTA 1201 GCTACGGTTT TCTTAGTAAA GTTATCGCCT TGTAATACCT TGATAATTTC AGCGTTATCA 1261 GTGTTATCAA CTAACTTTTG AAGTTGGTTC TTTACTTCAG ATACAATATC AACTTCTGAA 1321 TCGTCAACAA CTTCATTTGA TAGTGCAATC TTACCGGCAC GGGTCTTTAC ATCAAACTTC 1381 ACATCTTCAA ACATATTAGC GTCTACATCA GCAATTTCTG CTTGTTCTTC CTTAGTAGTA 1441 AGTACCGCTG TGTTGTAACG GGTAGCGATT GGATAATGAC CGGAACCAGT CCCTACAGTC 1501 TTTACAGTAG CGTACTTTGC TAAGTTATAA GCACTGTTCT TTAAGTCTAG GACTGGAGTA 1561 ACAACTTCTT CTGGAATAAC GGCTTCTGCC CCCTTAGTTG TTAATCCGTC ACGGGTTTCA 1621 CCACGTGAAC GAATGAAGCT TTCAAAGGCG TTAGCTGGTT GTTCTGTATT GTTTTTGGGG 1681 TCTAAGATTG TGTGTTGCAT TTTATTATGT TCCTCACTTT CGATAAATTG GTTGTAACTA 1741 CGAATGCTTG TTTTATCTAC ATCAACATTT GTCTGATCAT ATGAAGGCAC TGTAACGGTT 1801 GAAACCTCAA ATAAATCTTT AATCTGATTA ACGGTGCGTG TAATTTGTCC GTTGTCGTCA 1861 CGTGTCCAAC TGTCAGAACC ATCATCAACA TCAAAACGGA AAGACATAGA ATTAATGTTC 1921 CCATTCTTAA CATTATTAAG AGTGTCACTT GCGTAACTTA CACTTGGGTC AATAGTTGCC 1981 TTGAAGTGAA GCCCCTTATC GTCCACATCA AGTTGTAATG AACCAGCCTT AACGCTTGCT 2041 AGTGGCTTAG TGTAGTCGTG TTGATCAAGC ATAACTACAT TGGATAGGTC TACGTTATCA 2101 AGGGCGCTAG GGTCAATCAC TTCAACAAAA CCGCCTAAGT CCTTGCTGGG TTGATTAAAG 2161 AGTAACGCAT AGCCTTCAAC TGTATTAGGC TGTGAGGCTT GCGTTTCATC TTGGTTATCT 2221 TGCTGGTCTT TTGTTGGGTC TTCTTTAGGG CTTACCGTTT GTAAACCTGC GTTAGTTGTT 2281 AGTCGTTTCT CCATTGGCTG TAACTCCTCC TTCTTTTTCA ATAAAATTAT CTCCATTAGT 2341 TACCGGCACT AAATTAAGTA AGGCTCGGGC TTCATTGCGT GTGTAGATAC CGTTAACATA 2401 ACCATCAACT GCCATCTGCT GTTGAGCGGA CGGGTCAAGG CTTAATAGCT TGCTATTATC 2461 AAAGCTAAAA TCTTGCCCTA GCTTGTAGTT CAATTCAGAA GTAAAGCAAT CTTCATAGTG 2521 CTGTAAAGTA CCTTGTAAAT ACTGAACGTT ACTTTGTTGT TGGTTGCTAT GCTCGTTTTC 2581 TACACCTAAA CGCTCGGGTG GTAGTCCGAA CGCTTTCGCA ATTTGACGGG TATTCCAGTC 2641 ATTAGAATTT ACTAGCTTTA ACACGTCTGT ATTAAGTGGT AGGCTTTTAA CGTCCATACC 2701 ATCATCAGTA ACAATTGTGT TAAGTGAATT ATTGCCGGTA GTTGCCTCAT CAAATTGTTT 2761 TCTAATGTTC TCTTTACCAT CCGAACTAAG ATCAGCTTGG TGGACTTGGA CAACTGTTGT 2821 GCCATGAATT CCATTATTAA AGAATCCAGT CATTAACCTG TTTCCAGCCG CCTGTATCTT 2881 CATTTCATCT TTTAGCGCAT ACAGTGGCGA TAGTCCGACT AAACCATCAC GGGTAAAATA 2941 CTTAAAATGT AAGATGTTAG AAGAGGCAAT TACTCGCTTA ATACGTCCAT CTGGGCTGTA 3001 TGTGTAAGTC AGCTTTTGCG TTACATCATC TTGCTGGACA GTTAATTTAT TGTTAGGAAT 3061 AAAATTTAGC GTGTGTGAAC TTAAATCAAT TTCGGCAAAC GCATTACCAT TTAATAGCAT 3121 TTCAACCGCT AGGGCGTACT TGAAACTTCT GCCGTCCATT AACTCGTTAG GATGATCATT 3181 AATCATCTTG TTATATAGGC TAGAACTAGA CTTAATCGGA TTACTGGCAA GATCACCAGC 3241 CONTINUOUS ATTGCGACCAA ATATATCACT ATTACGTAAA GCCGAAGCAC TAACGTAACT 3301 ATTAGGGTCA TTACTAGAAA GACTTACTAG AGCGTCTAGA AAGGGGTCTT GTGCGCTTGT 3361 AGTCGTTGTT CTCTTACTAA ATAGGCCCAT TATCTACCCT CCTTTACTTG TGATTATCAG 3421 CONNECTED HELP AGCT EMERGENCY ERROR CONNECTIONS TTTCAACC CATCH ERROR ATCCCAAACA 3481 ACCAACCGGT TAATCCTATA GCACTGATCT CCATTAGAAC GCCTCCGGTG ATCAACAAAA 3541 CCGGTTTAAT ATAGCTAGAA AAGATTTTTA GCAGTTTCAT AGTATTCATT TGTACGTTCT 3601 TGCTCCTTTC TCTTAGTGAA GTAATCATAA CCAGCCGCCC AAGCATCCAT AAGAGCAGCA 3661 AGGCAATCTA TTTTATTG CTTTCTAGTC TTGTCTAATA ACGCTTGACC ATTAAAGTTA 3721 TATTTCAATA TTGCATTTCC TACGTTGTAA GCTAACATCT GATTGTTAGT GTGAAGATG 3781 TTACCAA TTAATCTTC CTTAAAAGTC CCAATTGGTA CCGATAAATT CTTATAGGAT 3841 TGTGTTAATT GAAGTTGTGG TAGTCCTGCC CGTTCAAAAC GATTAACAAG ATCAGCCCAT 3901 TTATAGGT CONTACT CONTACT TTTAGGAT ACTTACCGAT TAGGTCCATC 3961 ACGAAATCAT ATACGGAATC ATAATCAATC AAGCCACTTT CTAATGAACT ATACGGAATC 4021 TCTCCACGTT TAGCAGCCAT TTCATAATCA ATTCCATCAC GTTTTGATTT AGTAACAATT 4081 CCACCATAAC GAGATACAAA GGCGTGGGAA TCAGCGTAAA ACTTTCCATC TTCTAACGGA 4141 ACTAACCAAC TAATCGCCGT TAAATCTCGG CTTTTTGATA GATCAGCACC AATATAAACA 4201 TCTCTATTAC TAATATCTGG AGCTTTTTCA ATCAATCCAT GTTCCCAATC TTGCGTACTA 4261 ATATATGAAT TTTCATTCTG CTGTACAAAC ATATTCATAT TCTTTACAAG TACGTTATTA 4321 ATATTATTTT GTTTTGTGGC TACATCTAAA TCATTTTGAA TGTGTTCCCT CATTGTCTTA 4381 GCAATCTTAG GATTACTCAT CAAGGATTA GCTTTAATCC ACATTGTGGG GTCGAATATT 4441 TCTTCTTTTT TATCAAGACA ATACATAACC GCAAAGTAAC GATCATTCTT AATTTTGCCG 4501 TTGAGTATAT CGGCTGCATA GTCCCATTCA TTTTTGAAGG GTGAATTAAG ATTAAAACCA 4561 GCAGTAGAAA TAATCGCTAG AATACCATTG TCTTGTTGAG CCATACCTGA ATTCAAGGCG 4621 TTTAGAATAG TGTTATCTTT AGCTTGGTGA TATTCATCGA CTACGCCCAG TGTCGGGTTA 4681 TAACCGTCCG TACTGTGGGT ATCAGTAGAT AGTGGAATTG CGAAGCTACC TGTCTTTTTG 4741 TCAGTCACCC GTTGTTTATT GATTTTCACT CGTTGCCTTA AATACTTTGA ATTACGCCGT 4801 AAGTTTTCTA GTTGGTCACT CATAATATCA AACGCAAGGT GTGCCTGCTG GGAACTGTTA 4861 GCAGTAAATA GTATTTGTCG ATTACGGGCT GGTTGCTTTT CCATAAGAAG AGACACAACG 4921 CCAATCGCTG CCAGTAAGAA GCTCTTTCCA TTTTACGGG CTTCACTTAA ENDCCGA 4981 TTGAAGCGCA ATGAATTATC GTCTACCTGT CGCCAACCAT AGATATTAGA TAAGATAAAC 5041 ACTTCAAATG GCTCTAGCTT CAATGGTTCA CCGTTTGTTT GTGGTAAGCT CTCAACAAAT 5101 TTAATAACCT CHAPTER CGTTTCHAPTER TATATAACCT GAAAGTCATC GGTCTTTTGC 5161 TTTTTCATGT CGTCTAAGAA GCGCTGGCAA GCATGAATAA CTAACTTACC GGCGATTAAC 5221 TCACCTTTAA CAACTGAATT AGCATACTGA ATAGCTCTAT CCATTATGAC AACATCTCTT 5281 CAAACTCATC AGTAGGAGCT TCTTCACTCA TTGCCTTGTG GACTTCTAGG CGTACCCGTG 5341 ATTGTGGGCT AAGTGCCATT TGACTATCAA TTGACTTCAT TTCTTTAATA GCCTTATCAC 5401 GTGCCATGTA GTAAGGTGAC TGCTGTAATC CTCGTTTTGT ATCAATAACT ACCCCAGTAC 5461 GATCAATCTC TTTAGTACAT TTGATAATTG TTGAATACAA AGTACAGTGA GTAGCGATTA 5521 AACTAACATC TAGTTCGCTA ATAGGGGCAC TCTTCTTTAA GAGTGGGACA ATTCTACGCC 5581 ATTCCTTTTT TGCTACATCA TCAAGCCATT TAGGGGCGTG AGATGTTAAG TTTGGGTATT 5641 CTGCCAATGC TTTTTCAGCG TCTTCACGTT GTGCTTTTTC TGCCTTAGTA ATATGACCTT 5701 CTGGACGGGT CTTCATTGGT TGAGCCAACT ATTTAACCTC CTTCTATTTA TTTGGTGACA 5761 CCATGTCACT ATTTGTTTAA AAAAATAAAA AAAACATCAT TTCATATTCA ATTATCGTAT 5821 TATTTAACCC TTATTATACC ATATTTGAAT AGTTTGTTAA GTTCAATGCC TAAAAGTTAT 5881 AATAAAAAAT CCTTGACATT TGAGGCTCTA AATTATTTAA TAAAGTTGAA AAGAAAACCA 5941 TACAAAATAA AAAGAAACGT CTTGAAATCT TCGGATTTTA AGGCGTTTTT TTGTAAAGGG 6001 AGAATTTTTT TAAAAGAAAC CCCCACCATT ACGGCTCCTA CCGGTCTATA CCAATAGCGG 6061 GGGTATTAAA ATTATTTCAG CTATTCATAT TTATTTTCCT TTCTCGTTGA TGATCTTTTC 6121 TTGTCTTTTC TCGGTGACAA CGATAGCAAA GTGATTGTAG ATTAGTTGAA TCCAATCTTT 6181 TACTCCAATC TTCACGTATA GGTACAATGT GGTCAACTAA ATCAGCTTTT TTTACTATTC 6241 CCTTTCGTAA ACACATAACA CAAACTGGGC TTTTCTGGAG CGTTTGACGG CTTAATTTAA 6301 CCCACTTACT CGTTTTGTAG AATCTATTAT AGTCATGAGG AGCTTTGGCG CTTCTTTCCA 6361 TTCGCTTTTT GTATACTTTT CTATTGTATT CATGTTTCTG TTCTTTGGTC ATCTTTTTAT 6421 AGTTATCTCG TTGCCAATGT TTACGCTTGT CTTCATATTC TTTTTGTAGA TATTGATGTT 6481 TTTTACAAAA ATATTGACCT ACTGGAATCA CCTCTCGACA ACCAGCAGCA CTACAAAACC 6541 TTACTACACT CATTTGATAA CCTCCTATGA AAAAAGGGCA TCGCATAACA CGACACCCTT 6601 AGCACTTACT TATTAATTAA TTCCATTGCC TTACTATATG CTTCAAGCCT GCTTATGTGC 6661 CAGCTTTTAA CATCGTTAAC CGTTCTCTTA ATGCAAGCTT CAAGCTCCAT TGTATCGGCG 6721 CTGTAAGGGT CACACTCGCT TAGTCTATAC CTTGCCATCA TCACCCAGTC TTGGCGACTT 6781 TCCTCTGCGT CCTTGCATAC TGCCACTTGT GCAATACACT TTACTAGCTC TTGGTTGTCT 6841 GGTAGTCCTA GATCAATCGC TAATGGTAAT GGACTGCCAT TTACTGAGAC TAATTTTAAA 6901 CTATAAAGCG TAGTATACAT ATGATAATTA GAAGGATCAT CACCGCTTGC CTCAATCATT 6961 ACATTAATAA AGTTGTTATA CTCTGGGTGC GTGTTGACTG TTAATTTACT CATCCCCATT 7021 TCACCTCTTA TTTATGACTA TCAAGCTTGC GTAAGGTTAC AATATCATAC GCCAATAACT 7081 CATCATCAAT TGACCAACCA GCAACTTTAT AGATACTGCC ATTGTATTGT GCTTCTGGAT 7141 ATTTCTTCAT GTCCGTTAAA TCTTTCTTGT GACGAACTAC CAATATAACA TCATCAGTAA 7201 TTGAACTACC TGCCTCACTA ATAGCTTGAC TAGCACTGAT TGAATAGTTA CCACAATGTA 7261 CTGTCACATC TCCTACAAAA CCTGTCATGA TCATACCAGT ATTCGGGTTA CGTTTCCCCG 7321 TACCACCTTC ATGACCGAAT GTGACCTTAT GCTTTAATCG TGTAATTGCG TATTTATTAC 7381 TTCGCATTTA ATTATTCCTT TCTGCCTGTA CTTGCAGATA CAAGCAATAG TAGAACGTTT 7441 GCAGCCGTTC TAGTGAAATC TACTGTTACT TTATTTTTAA CTCCTTAATA GGCTTTTCAC 7501 CTATCCGGTG GTATGTGGTC ACTGCCTCAA AATAAAAGTA CGGTAAAAGC AGTTTTAATT 7561 GTTAATTTTC ATCTCTTCAA TTGAAAATAG TTTTTACTTT TATCGGTTAC CCCGTTTCAA 7621 GTACCCACAA TCGCCTTTAT ATCAACATTT ATATGGTAAC CGATAGGATA TAAAGGTAAC 7681 CGATACATTG CAGTTACTTA ATATAGTAAC CCGAAACTAT CGGTTACCTC AAAATGCTTT 7741 CGGTTACCTT TAAATAGCTT TATATCAAGC TTTATAAGAA CTTCTGCAAA GGTAACCGAT 7801 AAATATAAAA CTATAACTAA TTTTTAAGAG CAATTCCTTT ATAACCTTA ACATTTTTAC 7861 CGTTAATCTT AACTGTAGTG TGTTTGTATC CTCGTGCTAT TAGCTCTTTC GCAAACTTAC 7921 GATTACTAAG ACAAGGAACA GCAGTATTTT TACAATACTC TTTGTAATTA TCATATAGAT 7981 ATACTGATTT TTCTTTATCT TTCTCATTTG TAGTACAGCA ATCATTAATC CAATTACCGA 8041 TATTGTCATT AGCATTTACC CAGCTTCGCT TTTGCTGTTC CATGTATTCA GTCACTGGAA 8101 ACTTACCAGA ATCAAGTGCT TTTTTATAAG ATTTTAAGCA TTCATAGGCA AATGCTGGCA 8161 TTTCTCTTTT AAAGTCTTGC TCTTTGAATT GCTCTTTAAA ATGTTTAATC TTATGGAACG 8221 TTACAATAAT TGGTCGTCTT TTAAATCCGT CTGTAAAATC ATTGAAGGCT GGTAAATCAT 8281 TAGCGCTAAA AATCAATTTA GCTTCATTTT CAAGTTTAAA TGGATCTTTA TATTTAAATT 8341 GAGCTGTTGT AGTGTCGTCA CCAGTTAATG TTTTAATAAT ATTAGTCTGT TCCATAAATT 8401 TGGGGCTTAT ATCAGCAAAA ACATTAGCAG CTTTATGATA CAGCTGAGAA GTAGCAAATT 8461 TAGCTTCTTT TTGGTCGGAT AATGCTTCTA AAGAAACGTT TGAAACGTTA GGCTTCCCTA 8521 TTAACTCCAT TAGTTTATTT AGAAATGTAG ATTTACCATC CCCACCCAAC CCGTATAGAA 8581 TCATATAAAT TTGAAAGTCC TTAAAACTAC CTGCTAAAGC AAAACCAATA AAGGCTTTTA 8641 CTGTTTCAAT TGCTGTTAGG TCATATTCAT CTTGTAGTTT TCCAGTATCA TCACGGATTT 8701 CTTTAGTTGA GGGTACTAAT GATTGTTTTA ACCATTTATT CCACGTTGTA GCTTTTCCTT 8761 TTGTTTCTAA TTCATATGGT CTATTTTGTA AAAGATAGTT CTCTGGTGAA TTATCTTCTA 8821 AAGTGTCCGT CATCAAGTTG TAAGTGTGTT TACCAAACAC TGCTTTATAA GGTGCTGGTT 8881 GATCAAATGG ATTGTCTTCT ACAATTTCTT GTGAATCTAA GGCAATTAAT TTGAAAACCG 8941 ATGCTAATAA GTTCGTTCTC CATATTCCAT GAGGTACAAT TTCATTTTTG ATTGATTTTT 9001 CAATGACTGA ATCAGCGTAA TTTTTCCATT GTCTACTTTT AGGATCGAAC CAATAGCCGT 9061 GTTCTATAAA TTGGTTGGAT GTAAAGTGAT ACTTTTTTTC TAAATATTTA GCCAACTTAA 9121 TTTCATCAAC CAGTTTATTT CCTTTATCAC TTACAGTTAA CCATTCTGGA AAACTATTGT 9181 TATTTACTAA GTCATCAATA TTAGCCATAT TTTTCCTCTC TTTACATGGT AATTTAGCGT 9241 TTGTATTTAA GACTGATAAT CTCTACTTCG CCTTTTGTTT TGATATATTTC AAAGCTTTTC 9301 CCGTCTAAAC TTGTTTCTTC GTATATATTG TCCCAATCGA CTATTGATTG ATCTTCGTTT 9361 TGACTAGCAT TATTCCAATA CTTAAAGAGT GGTGTACGGT GCAGTATTCG GTTAACTTGT 9421 TTAACGTCAT CCCCTGTGTA GTAGAGAAGA TAAAAACACA TTGCACCAAT AGCAGGTTTA 9481 ACGCTATGAT ATTTATTTAG GTAGTAGGAA ATTATTTCCT CATTATTTTT ATAAAGAGCA 9541 ATAAATTTTC TACTACTTTT ACTACTAACA GCTCGTTCTA TAACCTGTTA ATCATCGTTA 9601 TAGTATTCAA GTGCTTTCTG AAACTGTTTC TTTGCGTACT CATTAAGGGG ATGTGACGTT 9661 GATTATA TTTTTTCCAT CTTGTCACTA TCTAATAAAG GATTACGGA TAGTTTTTCT 9721 TCAAAACTTA ACACTATTA TCACGTCCCA CCTATTGCAA TTGATCATGA ATTTGATCTA 9781 ACTTATCCAA CAAAATACTA ACTAGTGCTA ACAATGCTTT CTTACGTGAT ACTACTGTTT 9841 GAGCAACCGT AGACACTTGT TCATCACTCA TTGCTGCATA ATTGTCTACT CGTACAATTG 9901 GAGCAAAAAC ATCATTTAAC TGATCATACA GTGCTTGGGC TATTCCGGTT GTTTCTTCAA 9961 CATTGGAATC TGCTTCCCAC AACTGATTTT CAAACGCTAG TTCTTGGTTC TTATCTTTTT 10021 CCATTGTTTA AACCCTCCAC TCATGTTAGA ATGAAAGAGA ATTAAATTT AGTAATTCGT 10081 CCAACATCCC CCGTAAAGAT TGTTGGCTTT TTTATTAGCT AAATTTAATT CTCTAAGTTT 10141 TATTTAGTCG TTGTTAGTGT CTGAATTGGC GTTCTCACTA TCAACGGCTT TTTTATTACC 10201 ATCCATAAAG TCGTTTTCAA AATCAGTTAA AGTTTTATAT TGAATTGCTA AATCTTTAAT 10261 TTCTTTAGCG ACCTTAATAA TTTCATCTGC TGAGGAAATC GGATCATCTG CAATTATTTC 10321 TCCATTTTCT TTAGTGATAG TACCTTCAAA ACAATCTTCA GTAATTGAAT TTATATAACT 10381 GCCAGCTTTA ACAATCCTGT CTTCTATATC AATAATTCTT TTACTTAATA TTTCTTATTC 10441 AAATTTTTTA GTGTATAAAC TCATTTCTTA TTACTCCTTA AAATAAGTTA CTAATTGCAA 10501 CAACAATACC CAGCAATGGT AAAAACGTTG CTAGATAAGC CCAAAGGCGT TGGTCTGGTG 10561 AAGTCCACCA GTAAGCTAAA ATCTTACCAT CAATTTTTTG TAACATATGT CTCACCTCCT 10621 CCTATTTATT TCTCTACAAT CACTTGCCAG CCAGCTGTGC GATTATTACT TAGAATTTTC 10681 TTTTACCCAA CGGTCAACAT CTTCACGTTT ATATACATAT TTTCCTCCAA CCTTTGATGA 10741 TGGAAAATTT CGGGTCTTAA TCCAACGATC AATAGTTGTT CGGAAACAC TTAGATAATC 10801 CGCAGTTTGG CCCTTATTCA TAAACTCTGG TTCGGTTTTA ACAGTCTTAG CATCTTGTAA 10861 CTTATTGTTC TCTAGCTTTT TAGCCACAGC TTCAGCTAAC TGATCAATGA ACTGATCTAA 10921 AATAGCTGTA CTCATTATTA TCACCTCTTT ATTTCATATC GTAATTACAA TATATAACAT 10981 AATGAAATAT TATGCAACAA CAAAATAAAA TATATTGTGT TTTGTATTGT TATTTTCGGT 11041 TATGTATAAT ATATTAACTA TACAAGGAGG AATTAATGTG AAAGAAATTT CATCTGACCA 11101 GAAAATAGGT TCTAACATTG CACTAATTCG TAAAGCTAAA AAGATGACTC AAAAAGACTT 11161 AGCAAGAAAA ATTGGAATAT CACAACCAGC CTTGGGGAAT TATGAACGTG GCCAGCGGAT 11221 TATACCTGCT TCGATTTTTC ACAGTTTACC TCAAATATTA GATGTTCCTC TAGATTTTCT 11281 AGTCTATGGA ATTCCCAACA ATATTACCTT TCATGATTTA GCAACGCTCG ATTCCGTATC 11341 TCTCAAAAAG AAAGCTGCTC ATATTGAAAA TGATAGAAGT ATTATTGAAC GTGGGTTAGG 11401 GCGTGACGAC ATAAAAAGAC ATTTATTAGC TGCTGTTTTG CTTGATAATT ATGGTTATCT 11461 TGTGTACCCA GATGAATCTA GCAATGACAA AGAACATGAA CAACTTAAAA AATTTGTTTG 11521 GAATACATTA GATGGATTAC TTACCGGCGT ACCAATTACC AATGAAATAA ATTTTAAACA 11581 AATTAATGAA CAATTTGAAT TACTTGCAAA TACGTATTTA AGCCTAATTA TTGACGAAGA 11641 GGCAAATCGC TATCCTGCTT TCCGCAAGGA TTTACCACCC TTCAAAGAAA AACTTACACA 11701 GTTTTAAAT GATAACGGAT ATTTAAAAAT TTTAAAAAAA TATTTAAA CCTTTCTCTA 11761 CAATCTCTTG CCAGCCAGCT GTGCGATTGT AGGAGGAAAG TAAAAATGTC AGTATACAAG 11821 CHATAAAGAA ATGGTACGTG GTATGTTAAA TACCGCATTA ATGGTAAATC AACCAGTAAG 11881 CGAGGTTTCA AATTAAAATC GGACGCTGTA GCGTGGGAAC AAGAAAAAGC TGTGGAGCTT 11941 AAAAAATATG GTCAAATGAA TAACCATAAC ATGACCGTTG AAGAGCTATC AAAAAAATGG 12001 TTGCCAGTAT ATTACK TGGGATAGAA ATTCTACTTA TTCATAAAAC AAAACAAATC 12061 ATTAAAAATC ATATTCTACC CCGCATTGGA AACTATAAG TTGCTGATCT TAGCATTGAG 12121 TTATTAACTG AAGTTGCTGC TAAATGGAAA QUICK TRACK CCCTTTTAAC 12181 TATACTAAGC GAATGTTAGA CTACGCAGTA CHARTAGAG CGATCCCAAC TAATCCAATG 12241 AATTCTGTAG TAAAGCCTCG TAAAAAACAT CONVERSATION TTACTAACAA TAATTTCTTT 12301 AATGAAAAAGC AACTTCACAA TTTTATCAAG TGTATAAAAA AAGACTACGA AGAAAAAAAAT 12361 CCTCGTGCTT TCATGGTTCT ATGGTTAGCC CTTTTTACTG GCATGAGAAA ACAAGAACTT 12421 CAAGCCTTGA CGTGGCAAGA TGTTAAATTT ACAAAAAGCG GTGGAATAAT CCATATTAAC 12481 AAGGCTATTA AGAACGCAAA ACATCCCTAT CTTGGTGGCC CTAAAACCGC TAACTCTTAT 12541 CGCTGGATTT CAATAGATAA AAAAACTGCT TCCTATCTAA AAAGATGGAA ACAGCAACAG 12601 ATAGATATTT TAACTAAACT AGGTTTTAAT CCACACCAAA AAGAGCAATT GATTTTCTCT 12661 ACCTACACTA AAAATAAAAT TGTTTTAGGT GCAGAATTGG ACAAGCCGTT AAATAAAGTA 12721 ATTGTTAGAA ATAATCTAAA GAAAGTTACA TTCCATGGAT TACGTCATAC CCATGCTACA 12781 CATTTGGCTT CTATTGGTAC CCAGCCAAAA TTAATAGCAG ATAGATTAGG CGATACAATG 12841 GAAACTGTTC TTGAAGTTTA TATTAATGCA GATACTGAAC CAGAACAAGG AATCGCCGAC 12901 AAGTTCGCCG ATAGTTTAGT ATAA (SEQ ID NO: 12). Bacteriophage locus 6 has the following sequence: 1 TTAAAATTGA CTAAGTGCCT GGACGATTTT GTCATCAGTT TTACTTTTAT ATTCATCAAT 61 CAAGTAGGCG TATGTGTTCA TTGTGGTTGT GATATCATTA TGTCCAAGTC TCTTGCTAAT 121 TGCATAAATA TCTATTCCGT TACTTAACAG TAAAGCAACG TGACTATGAC GTAAACTATG 181 GAAATGAAAA TTCTTCTTTG ATAATTTTGT ATCACTCATA ATTTGTCGAA GCGTTTTATT 241 TAATGCTGTA CTAGTAGGGA TAGTATTAAA TTGATCCATA AAAACAAGGT TACTTGATGA 301 ATTATTGCGC AATTGTTTAA GTAGTAATAG TAGTTTTTCA TTAACTTTTA TTTTACGTGT 361 AGATGATTCA TTCTTGGTGG GTTTAAAGCG ATGTGTATTA AAATGTTCGT CTGTTTCGTC 421 TCTTCCTTTT ACCTCTCTCC ATGCTTTATC AATATTAATG GTATGATGAA TGAAATCAAT 481 ATCATTCCAG GTAAGAGCTT GAATTTCTTC TTTTCTCATT CCAGTATATA TCGCAGTGAC 541 TATCATATAA CGGCTTGTAT ATCTTCTATT AGTAATTCCA TTGATTGTAG TAGTTAATAA 601 TTTCCTTATT TCAGTTACAT TAGGGTATTC TACCTTCATT GTTTTGCTAG TATTGGCAGC 661 TAAAGTAACA CCTTTAGTAA AATCTTTAAG CAGATAATCA TCAAGGATAG CAGATTGTAC 721 GCAAGACCGT ATTATTGAAT TAAGCTTCTT TACACTTGCT ATAGCATGAG TTGCTCCATA 781 CTTGTTAATA AATTCTTGAT ATTTAGAACG GTTAATTTCT TTAATAGAAG CTTCTTTGAA 841 ATAATCATTA ATTAGATTAC CGATTATAAT ATAACGATTC AGAGTTACAC TTGATATTTT 901 AGGTTGCTTA TAAGTATTAA CCCATTCTTC GTAATAATCA CTAAAAGCAA TTTTTTCTC 961 AATGTGTATT CCGCGATTAA GATTAGTTTC CATTTCAGCT GCCCACTTTT TAGCTAGTGC 1021 TTTTGTTGCA AAACCAGCTT TGGACTTTGA AAAACGTTTT CCTTCAGTAT CTTTCCACTG 1081 AATTCTTACA GACCATTTTC CGCTTCTTTT ATATATTTGA GCCATACTTG TCCCTCCATT 1141 ATTAAATTGT GTATAATGAA AGGGTTGATA GAATTTGTTT GGACGCAATT AATATCAACC 1201 CTTGGTCCAC TGACAGTTGC CGCTGTCGGT GGGCTTTTTT AGTTTAAATA GCTTTTTACG 1261 TCATCAATTT AGTTGGACGA GAAATTTAGC TTTTGTTTAG CTTCTTTAAT TGATTAATAA 1321 TTTCTTGATT TTGCTTAATT GTTATCCAAT TTTGCTGTTT GATTATTCTT AATTCATGAA 1381 AAAGGGCTTT TGTATCATTA CTTGTAAAAG TAGGATAGGC ACCTGTTAAT TTTTCGGCAA 1441 CTGCTATATC TTTTACAGAT TCGAGAATTT CGTCATCTAA ACTTTCTAAA CGATTTTCTT 1501 TAATATATT ATCTTTGTCT TTAGCAAATC CATCTTTACC ATTGAAAATA CTCATTTTTA 1561 GCTTTCTCCT ATCTTTTTAA TTTTTACATT GTAAAGAGCG TTATTTAAAT CATTACAGTT 1621 CCTAAGATAG GAAAAAGCGT TTTTTAAAAG TTTATTCATC CTTTGACTCC TTATATTCCT 1681 AAAATTTGTT TCTTTTTAGC ATCAAATTCT TCTTTGTTAA TGATTCCATC ATCAAGTAGT 1741 TGTTTTAATT CTCTTAATTG CGAAAGGTCA TTACTAGAAAT TGGATTGTGC TGATGTCTGC 1801 TTAAAATCTG CAGCTGCCTG TTTAATAGTC TCAGCCATCT TTTTAGCAGG GTAGGGTTGC 1861 ATATTTTCTA TTTGAGTTGT AATAGCTCCG TTGGTTACTG CAATAGATCC CAACATTAAA 1921 CCTTTAGAAT ATGAAACGCC ATTAATCATA TCAAGGGGAA TGTCAGTTGA TTTACTACCA 1981 TAAATCAGGC CGTGGTCAAG AAAAATTACG CGCTTATTAG TACAAACCGC AAGAATGGAA 2041 TTAGTTTCAA CGAAAGCATT AGCAGCATAA AGTATTTTTT CTCCACCATC GACATCTATT 2101 ATGTCTGGCA AGGCTTTGAT TTCCTTTTTA GTACCGAATA GATTTTCTAC ATTGGCATCC 2161 TTTAACTGTT GCTTAATAAC ATCCAATTTT TCTTGTTCGC CTTTGTTGAT TTCGTCAATT 2221 GCTGCTTGTA AAGTATCAGC TTTTTTACCA GCGCTATCAG CAATTGAATC AAGTTTCTCA 2281 GTTACTTTAG ATAGCTTTGA TTTATACAAA TCAGGATGTT CTTTGTAAGG TACGGTAGAA 2341 TGAATCCCTA ATAAACTTTC AATTTCACTA GCGGTATGGG AACTAATGAA ATTGCTAAGT 2401 TTAATTGGAA CACGGTAAGT ATTTGCTGGA CGTTTGGGAT CAAGTCTGTT GGCATCTTTG 2461 CCACAAATTA AATATCCATC TTTGGTAATG CAAGAAGCCT TTAACATTCC CAGGGCATCA 2521 TTACATATGA AGCATCTCTT TTTACTCATT TGGATCACCT TATTCCATTG TCACTGAATA 2581 TTTAACTAAT TTACCAACAA TTCGACCTGG ATGCTCTTCA TCAAGAATTA TTGGATCATA 2641 GTTTTTATTA TCTGGCATTA GCATAACTAA ATTGCCTTGA TGCTTAATAC GTTTTAAAGT 2701 AGCTTCGTTA TCATCGTCAA CAAGAACTGC AGCTATCTCA CCATCTTCAA CTTCAGGTTG 2761 CTCTCTAATA ATGGCTAATG CGCCATTAGG AATGGTAGGC TCCATGCTAT CACCTTTACA 2821 ACGAAGACCA AAAAGTGTTC CACTAGGAAC TGGTTTTTCA AAGATTTCAT CAGTATAACC 2881 TTCGATATTT TCTTCAGCAG TAATCGGATC GCCACAAGCA ATTTCACCAA TGATTGGAAT 2941 TGAAACAACT TCTAATCCTT CTTTAGGATA AATAATTA GAAGGTTTCT TTTCTCTGGT 3001 DOWNLOAD TCATTAAATA AATTTCAGCT AATTTAAATA AAACATCTTG 3061 ATTTGCCTTT CTAGATCCTA ACTCATATCT AGTCACAGTT GCTCTTGTCG TATCAAGTTT 3121 GTCTGCAAGT TGTTCTACTG AAAGGCCACG TTGTTCACGA AAATTTCTGA TTTTTTGACC 3181 AATGAATTA CTTAGTTCCA TTTTATGTAC CTCTCTTATG TAACTAATTA TATAACTTGC 3241 GTTACCGAAA TGGAATTT TTTATCTTTT TCGAAAAAAA TAGTTGCATT TGTTCCAGAA 3301 TGGTTTAT ATATAATGTGT TCCAAATTGG AACGGAAAGG AGAGATAATA TGCAGTCAAG 3361 ATTACKGAT TTACGAAAAC ATGTTAAAGG ATTTACTCAA WINDGG CTGATTATCT 3421 AAATATTAGT GTCAAAGCTT ATCGTGATAA GGAAAATGGT AAAAATCAAT TTACTCAAGA 3481 TGAAATGTTT GCTATTAGTA AATTATTTGA TCTTAATATT GACACTATTT TTTTGCCTCG 3541 TAAGTTCCAT ATTGGAACAA AGGGCTAAGA GAGGTGACAC AAAATGCAAG CATCGCTAGA 3601 TEXTTAGE TTACTAATGA GGTTCTCAGG CGTATTAAGG AATGTTACAA 3661 CTTAGTGCCT AAACAAGATG TCCAAACTGA CAAATGGGTC GGTATCAAGG AATTCACGAG 3721 TAAGTTGCCC GTTATAAAGG ACAAGGAATG GGTCAGAATG TTTCTCCTTA CACTTCCAGT 3781 CTTTAAGAAC TGGGTTATCA ATTTGAATGC AGGTCAAGGT CATCGAACTA AGGTAAATGT 3841 GACCAAGGCA TTGCCTTGGA TTATGTCTCA TCAAGCTGAT ATTGATTGGA ACCAGTCATT 3901 GCCACGTTAG GAGGTGAACA GATGGCACAA CCGATATTTG TAAAAGGAAT TTTTGGAAGA 3961 CGAATTATAG TTTCTCAATT TGAACAAACG TCTGATTTTA TTTTGCAAAA GAAAAACGCT 4021 GACCTAATAA AAGAAGCCAG CGGATTTTCA AAAAACAAGA AATTGTTTAC TCGTTATCAA 4081 GGTAAAGACT TTCAAATTAT GGAGCAATTA AAGTGGCAAC CCAGTGTTCT TTTTGATGAT 4141 GCCAGTAAGA ACCGTAGTAG CCACAGATTT AAGGACACCA ATGGAAACTG ACTTTAGAGT 4201 GTTAGTAGCT TTCTTTGTTT GTTTCCAAAC CTCATCATCT CGAATGGAAT CAAGTAGTTC 4261 ATGCCCAGAC CAAGTGATGT CATAGACAGT TAATTGGCGA ACCATTTTAT TAATAAATGG 4321 TTTGGCACTA ATGAAACCGC CTGAGTAGAG CTGATAAAGG GTATAAACAA TATCATTTTT 4381 ATCAAAGGTC TCATTAGCAA TAACATTTGC AATTTGAGAA TCTGTAAAAC CTTGGTAAAG 4441 CATTTGCAAT TGCTGTTTTT CTAATGATAA AAGAACATAC CTAACACAGT CTTGCTTCAA 4501 TTTCACAATT TTCACCACCT TTATTTTGAA TTAATCAAAG TATAGCAGAA AGGGAGAGCA 4561 GTTAAATGGC GTTGGTAATT GGATTACCAA TATTAATTAT TGCAATGTGT TTGTTATATG 4621 CATTGGTGTA CAGCTTATTG TATGAGCGGA ATAAACCATT GCTATTGAAA GAAAAGTATC 4681 GGAAGAAACA TTGAAAGGAG GTGATATGAA CTTTGGTAAA TTTATTTCTT TTGTTGTTTT 4741 TTATCTTTGT TATAATGCCG CTTTTGTATC AATTTTTGAA TTACATCAGA AGGCAAATTG 4801 AAAATTTCTT TTGGAAAAAA AGCCATAAAAA ATAAGAACGA ATGAAATGAA AGTAGCTGTA 4861 AATTCAAATT GTTCTTTGGT CTGAGTTATT AATAGCCCAG TAATAGTAGA AAGAATAATT 4921 GCTATTTTTG AAAGATCATC CAAGTATTTT TCGCTATTT GAAATCCTAA AGTTTCTGTA 4981 AGCCAGCCAA GGATAAACAA TGGAAAAGAA AAGAAGCCAG TTAGAAAAAG AATAGTAATT 5041 AAGCAATCAA ATATTCTGAG TTTTTGGAAT TCAAAATTA CAGCATCTGG ATTAGCAGCA 5101 TATGTAATAT GTAGAGCTAA ATAAGTAAAA CAGATGAGGC AGAAGATACA AACCATAAAG 5161 TCGGTTAGTT TCTTACTATA GTAATTAAAT TTGGTTAAAA ACTTAAAAAAT TTTACGCATA 5221 ATGATTTTCC TTTTGTACTG AGTTAATCAA AGTATAGCAA ATGAAAGGAT GGTAGTTTAA 5281 TGAGTAAATT AATTGCGCTA ATCGTTGGTG CTTGGATCAT GTATTGTCA ATGATTGGCT 5341 CTTATGATGG AGCGATGGCG ATCCTAGCAG TTTATCTTCT GCTAGTGGTT CTTGATCCAC 5401 TAAATAAAAA AGGTACGACT GCCGCAAACA GTCGTACCGA TAAATAAATA ATCTACGAGG 5461 TAATTATA TGAATGAGTT TAATTTATCA AAATTAAATG CCAGGGTTGG CGATAATTGT 5521 GTATTTGTAT CGAATTTGGC AGTTCGCTAT CAAAGCGCTG CTACTCCTGA AGAGCGAATG 5581 GCAATGGCCA TCAAAATGGA GAATGCTGCT ACGATGTTAC GCATTTCAGC TGAGCGTTTG 5641 GCCACTGAAA CTAAGAATGT TTACGGAGGT AAGAACAATG ACTAACGAAG AAAAGATTAA 5701 GGCAATTAAA CAAATTCTTG GACCAGAATA CGAGGAGGTA GCCATTTTCG CTGCTAAAAA 5761 ATCAGAAATT CGTGACGAAC GTACTAATTC ATTAGTTGAT GCGGATCCCG GAACGGTAGC 5821 AGCCATGATT ATGAATGGT TARGET TCCGATAGCA GCTTCAATTG TCAAAAGACAC 5881 TATTGATACT TTGGAAACTG ATCCAACTGC TGATTTATTT GCACAGATTT TTCTAGGAGG 5941 WINDOW TGROUND TGGATTAAC QUESTIONNAIRE AAACACTTGC GROUP TAGCGGGAT 6001 GACTTAGATC CAACTATTCT AAAGGATACA TTGGAATCAA TTAAGGATGA TCGGAAGACC 6061 AAATTGGACA ATCTTGCTTC ATGGGCAGAT ASSISTANCE CAGAAATTGA TTTTATGACC 6121 AGAAAAAGA AGTCATGGGA AGAAATT ACTTACCGAA AAAATAAACT TACTTGGATC 6181 AAGAAATATA TTACTGAAGT TCTTGATGAT GCCGGTATTA AGAAATATAAC TACTGAAAAT 6241 CACTTACTTA GTGCCCGGAA CTTTAAGGCC TCCACTTA TTGATAGTGA TAGAAGCTT 6301 CCGGATAAGT TCAAAATTAC TGAGACGACT ACTAAGCCAG ATAAGCAGGC CATTTACCAA 6361 GCACTCAAAG CTGGAGAAGA AGTACCAGGA GCACATTTAA AAGCTAACCG TAACACGGTG 6421 CONTACT GTTTGAACTC CGTGATTATC CONNECT ACCATCH ATCATTATC 6481 CTATAAGTGC TGGTCACCGT TCTATCATGG TTCAACAGCC GCCACGAACG GGGAAGACAG 6541 TTATTATGGC CGAGATTGCT AGACGAGCAA CGGCAAAGGG TAACCGTATC TTGTTCGTGG 6601 TTCATCGGCA AGAAATTGTC CAGCAGGTTA TCAAGACTTT CAAAGCTAAT GATGTAAATA 6661 TGGATTTAGC TAAAATCGGC ATGGTTCAAA CGATTACCCG ACACGTTAAT AATTTGGACC 6721 CACCGGCGAT AATTTTTGTT GATGAGGCCC ATCATGTTCT GGCTAAATCA TATCGAAGGA 6781 TTCTTGATGC TTTTCCGAAA GCTTATAAGT TACTGTTTAC CGCTACTCCT TATCGGTTAG 6841 GTGGACAGGG TTTTACTGAT GTGGCTGATG ATTTAATTAT TGGCAAATCA GTCCCCTGGT 6901 TAATTGACCA TCACTTTTTA GCACCAGTTG ATTATTACGC TCCTTCTTAC ATTGATACTG 6961 CCAAGTTAAA AGTAAAACGA ACTGGTGAAT ATGACACTGA TTCAATCAAA AAAGCCATGA 7021 AGCCTAAAAT CTACGGGAAT GCGGTTAAGC ACTATTTGAA ACTTGCTACG GGAATGCAAG 7081 CCATTGCCTA TACCTATAAC GTTGATAGTG CAATTAAGTT AGCCAATGCA TTTAATGGCT 7141 ATGGGATAAC TGCAAGCGCC GTTTCCGGAA AAACGCCCAA AGAAGAACGG AATAAAATCA 7201 TTGAGGACTA TCGCCAAGGA AAAATTCAAA TTGTAACCAA TGCAGAATTA TTTACAGAGG 7261 GCCTAGATTT ACCAAATGTT GATTGTGTCA TTATGTTACG GCCAACTCAA TCATTATCGT 7321 TGTACTTACA ATTTGCAATG CGCTCAATGA ATCCACGGGA AGGTAAGACT GCAATAATTA 7381 TCGATCACGT GGGAAATGTT GAACGATTCG GGCTGCCGAC TGATGAGCGG CAATGGACAT 7441 TAGAAGGTAG CGGAAAAAAT AAACAACAAC CAGGAACAAC GCTTAAACCT GTATCAGTAT 7501 GTCCGATATG TTTTGCTTCG TTTTATCGTA CAAGTGATAT TTGCCCTTAT TGCGGGGCGG 7561 CATTAGGAGA AGAAAAAGAA ATTGAAGTCG TTGATGATGT TCAACTAAAA AAAGTTACTA 7621 AGTCACGGCT AGCGATTATT AAGAAAATTC AATCGTCAGC AATTATGAAT AATGTTGCTG 7681 GCAAGCGTCC AAACGAATTG AAGAATCTGA AAGAAATACA AGCCTATGCC AAATTAAAAG 7741 GTTACAAACC AGGCTGGGCT TACCACTACG CTAAACAGCG TGGATTTATT AAGAAGTGAG 7801 GTTGATATTA TGAGTATTTT GCCACCAAAT AAGCCACAGA AGGCACGGCG AGTTCCAAGA 7861 AATTACTTTA TCTACGGAGA TACAATGTCC GGAAAGTCAT ATCTAGCTGA ACGTTTTCCA 7921 AGTCCGCTAT TTCTTAACAC CGATGGTAAT AGTGAGATGA ACACCGCACC AAGTATTCAA 7981 TTAAAGAATG TCCGAAAGAG CGATGGAAGC TTGAAAGAGT CAGTGATTGA TCAACTAGAC 8041 AAGATTATTC TTGCTCTTGG TACTGAAAAT CATGGTTACA AAACAGTAGT TATTGATGTG 8101 SETGATG QUALITATION AATTQUET GCCATCTGTT SETGG ATTACK AACG 8161 CTGGGGGATG TTCCTTACGG CAAGGGATAT GCACAATTTA ATACCGTCTT TCAAGCATTT 8221 GTCACTGAGC TAAAAGCCTT ACCACTGAAT ACGGTTTACA TTAGCCGGTT AATGATGCTA 8281 ACTGROUP CTTCTGGCCA CHANGE CLASS CLASS CLASS ATTACK 8341 GTGGTTAACG GAAATTGTGA TTTAGTGATT GAAACTAAGC GCTATGGTGA CCGTTATATC 8401 CGGATGGTTA AAGATCGACG AATTCATTAT GTCAAAGATG ATATTACTGA TCCGGCAATC 8461 TTACGGGTAC TTGAACATGT AAATGGCGTC TTTGATAAGC CAAAGCAGAC TACTACAAAA 8521 EXTENSION AAATTGTTAA CHAAATTAA AAGCAAAATG INTERNATIONAL THRESHOLD 8581 MULTIPLICATION MULTIPLICATION MULTIPLICATION AGCT ACTmultiplication TTGATCCAAA MULTIPLICATIONCA 8641 GTTAATAAAT TTAAGGGACT GGAAAGTGGT AAATATACCG TTGTAGTTGC AAAAGTAGAA 8701 AACCATGAAA CTCCTTGGAA TGCTGAACAG CTTAACTTTG AGTTAGAAGT TGTCGATGGA 8761 GAATCAGCCG GCCAAAAAGA ATTCTTACAA ATTGGATTAG ATGATTAC TTCTAAGGGT 8821 AATCCAATC CAATGCTAGA AACTAATT CGATTGGTTT CTAAGTTAGC AGCAATTCTA 8881 GGTGTTGAAA TTCCCGATGA AGTTTGGGAT GACGATACTT TAATCTACGA GAACTTGGCT 8941 AAAGCATTTG CACCGGCAGT ATTAGACC ATGATTATGG ATTTGAAGGT TCGACCAAAC 9001 AAGAAGAACC CCCAATCC ATACCGTAAT TATGACTTTG ATGAAGCGGA ACAGCCGGAA 9061 ACGCCAGAAG TTACAGATGA TGAAATGCCC TTTTAAGTAA ATATTTGAGT CAGTGAACTT 9121 ATTACKCCGT ATGGCTGGGA GGCCATTAAG GAGGAAAAAAT GAAAAATCTA GTTAATTACG 9181 CCTTAGCCTA TCAAGCAAAG GGTTTAAGCG TCCTCCCAAT TGCTGGCAAG CGTCCACTAA 9241 TTAAGTTTGC TGATCGTGAT CCACTACCG CCGAAGAAAT AAGACCATC TGGATAGAAC 9301 ATCCATATGC TCAAATTGCG TTGCGGACTG ATAAGTTCTT CGTTGTTGAT ATAGCCCGCA 9361 ACCATGCTGA TACATTGAT GGTTTTGAAT ATTACCAGCG GAATATTTTC 9421 CGGAAACTTT AACCAAAACC ACCAAGCATG GTGGCCGACA GTTATTTTAT TTGAAACGTT 9481 CAGATATGCG AGTTAATCAG TTAATTGGTT ATTTACCAGG TGTTGATGTA AAGGCCCACC 9541 AAAATAATTA TGTTGTGGTT GCGCCATCAG AAGGTTACCA ATGGCTGAAT AAGAAGCCGA 9601 TTGTTACGGC TCCTAAGTCG TTAGTAGTGA ATATTAACCA AATGCGAGCC AGTAACCGGC 9661 GAAGTTCTCC NATIONAL GTTTTTAAAC CACGTGAACG CAACTCAACT ACTGACTTAC 9721 TTGACCAT CGCAAATGGA TTGGGATA AAGGATAAG AAATAAAAAC TTAGCTGGAA 9781 TGATTGGTGC TTTATTGTTT CGGGGAGTAG AACCAAAGTC TGCTTATCAA TTAGCGATGA 9841 TTTGTAATGA GAATACGCCC GATCCACTAC CAGAAAGA AGTGAACCGG ACATTTCAAT 9901 CAATGCTAAG ACGTGATTTG AGAAACGGGG GTGAAATACG TGGCGGATAA TATAATTCGC 9961 AAACCAATTG AATTTGATT AAATACTCAA GGCAATCCTA AAACTAATAG TTTGAAT 10021 ATTGGTTTAA TCCTTGATGG CGATCCACTA CTGCATGGCA CCTTCAAATA TAACGAGTTT 10081 GCTTATTCAA TTGATGTTGT TAAGCATT CCACAGCTAT TTATTGAAAA GGGGCAACTT 10141 BUYCT ATTCAGCAAT TATGCTCCGT TACATTGAGG ATGAGGG GGTGATGTTT 10201 CAAGAAAAAT TGTTAAATAT GGCAATCACT GTTGAAGCAA AAAGCCACCC ATATAATCCG 10261 GTTAAAGAGT ATATGGAAAA GTGCTATAAG AATTGGGACC ACAAAGAACG AATCAAAGAC 10321 TTCCTACCAG TCTATTTAGG AGTACCCAGT GGTGAAGTAA CAACGCTGCA GACAAAATTA 10381 TTCTTAGTCG GAGCGGTGAT GAAAGTCTAT AAGCCGGAAA GTAAATTTGA TTGGGTGTTT 10441 GATTTAGTTG GTGGCCAAGG CGTTGGTAAA ACTACTTTAC TTAAAAAGTT AGCCCATGGT 10501 TGGTATACAG ACCAATTTAC GGACTTCAAA GACAAGGATA ATTTTGCCAA TATGCTGCGG 10561 GCATTGATTG TTAATGACGA TGAAATGACG GCCACAAATA ATTCTGACTT TGAAAATTTG 10621 AGAAATTTA TCTCAGCTGA AGAATTAGAG TTCCGGCCAC CATATGGACG ACATACAATC 10681 CGCCGGCCAA AGAATTTTGT TATGGCCCGG ACTACTAACG AATCAACCTA TTTGAAAGAT 10741 AAAACCGGTG AGCGGCGTTT CTTACCTAAC ATGGCTGATA AGTCCCAAGC AATGGCTAAT 10801 CCGGTAACTG ATCTTGATGA TACGATGGTC AATCACATTT GGGGTGAAGC TGTTGGCCTC 10861 TACAAAGAAG GCTTTTCTTT CATATTGACG AAGGAGCAGC AGAAGCTCAT TGAGGATAAT 10921 CGAAAGATAT TTATGTACAT TGATGAAACT GAAAATCAAA TTGAACGGGT TCTCAGTACT 10981 TGGGACGATG ACTGGATTGA AAGCTCAGAA ATTGCTCATC AATTAGGTGA AGATAATCTG 11041 GTTAAGAATC GTTCATTAGC CAAAAAGATT AAGTATGTAA TGGATAACCG GCATGATTGG 11101 AAAGCAGGAC AACGGCGAAT TAAAGGAATT AGTCATCGTG GTTATAGAAA AGTGCATACA 11161 GATAATACAC TATGAATATA GTTAAGTGTA TGCAGAAAAA ACCTATTACA TCAACGTTTA 11221 TTAAGGTTTG CATACACTAC TACACTATTT TAATAATAAA AAATAAATAT ATATAAATAC 11281 TATATATGCG TTATAAAAAAG TTGAAAGTTA GTGTATGCGT GTATGCAGTA ACTAAATCCG 11341 TTGAGAGAGT AAGAATTAAG CTGTATACAC TACTGTATGC ATAGTGTATG CAAGGAGGAA 11401 AATATGAAATG AATTAAAAAA CATCAGCACA TCAGAATTAC TTGATGAACT GATTGAACGT 11461 AATGCATTAT TTCGTGTAGA TTGTGGTCTT TATCGGAATT GGGAGTTGAA GGGAAAATAT 11521 SUPPORT ATTAAATT GCCTAGCGCA TATCCTATTT ATGTAGGAAA TTCATTAT 11581 ERROR TTAAGTGGGA GTGTERROR ERROR TTAAGTGGGA ACATAAAATT CAAAACQUESTION 11641 TCCGGGTTGC ACTATCAAAA CATCAGTGTA CAGTGTTCCG GGTAAATGTC GGTTCGGTAA 11701 AAACACCAGA TGGAAGATTT TTTTCAGCTG GTGTACCTAG TGGTCACCCG GACTTATATG 11761 GATTTCGTTG GTCGGATCAT CAAGTATTTT ATATTGAGT GAAAAACGAA AAAGGTAAGC 11821 CTAGAGCGGA TCAAATTAGA TTTCATGAAA TGCTAACTAA ACGAAATT ATTCATGGAA 11881 TCGCTAGGTC TGCTGGAGAT GCAGTAAAAA TTGTTGAGGA AGGATTGATT GGTTATGGAT 11941 ATGAAATAAAAAAAGAACCA STORM WINDOW TGAAATAAT WEATHER WINDOW 12001 CCTCTCGTGG AGCTGGAACA AAGGAGGATC CGATAGAAA GATTATTCAG TATTGGAGCA 12061 AAGAAGGCAC ATTATTAGCA AAAGTTTTG GAAACTAATT TTTCTTTGAG TCACGTTTCT 12121 CTATGTGCTT TAGTTGTTTT TCAGGAAGAC TATTATAAAA CTTATCAATT TGATTTGGCT 12181 GTGTTATTAA ATTGTCTGTA ATTATTTA ACAGATTAA AAGACTTTTC GCCATTTCTT 12241 GGTTATCAGT TAAGTCTATC TCACCAGGAT GAACAGCATT ATTTCCAACA ATTCTTACAA 12301 TATCAAACGC TTGTTGTAAT TTAGCCGGAA GTCCCTTAGA TACTAGATCA CCAATACGAT 12361 TATCTAATGA ATGTTTATTG GAAAATTCTT TTGTTAGTTT ATCTATTGCC AGACGAGACA 12421 AAGCAGCAGA TGCTCTTGGT GAATCTCTAA GTACTTTTGC CGCTTCAATA TAAATTTGTT 12481 TAATATCATC GGGCATATCT GGATTAGGAG CTGTTAATTT TAAAGGAAAA CTAGGAAAGA 12541 TAAGTATATC TTCATTGGAT TGCCGATTAT GAAACCAAAT AGAATCTAAA TAACATGAAG 12601 TGCATTTTGC AACTATTAAA TTATATTCGT ATTGTTTTGA TTTTATTTTT TCTGCATATT 12661 TCCAATCAAA TTGAGCATAT ACATGACAAT AAGGACAAAT AATAGGAGCT TTCCCTGTAA 12721 AATCATTACT AAAAATATTTA GTCATTAAAT TCACCTCAAA TAAGATTATA GCGTAAAGGA 12781 GTAGATGTAA TGCTACACAA ATATAGAAAG TTACCAATTG TGGAAGCTGA ACAGTTTGAT 12841 GGGTCAGATG AAATGATTGA AAGGTATTCA GTGCATGTAT TTAATCCTAA TTTAGCTAAAA 12901 AACATCTTCT TTATAGGTAT GAACGTTCTA GCTATTGGTG ATTGGATTGT TAAGGATGAA 12961 TATGGGAATT ATCAAGTGGT AGCTGATGAT ATATTCCGTA AAAGTTATGA GAGGTGCGAC 13021 TAATGCACAT TTATGAAGTA ATCGTTGTAG CTGTATTTG CACAGATATT AGCCACTTTG 13081 TTGTTGCTAA GAATGCCGAT AATGCTAAA AAATTATTCT TGATTATTAC AGCACTCGTG 13141 ATGATGGTAT CAGGCCAACT GTGACAATGT ATGACCTAAC AACAAATTA ATCAATCTTA 13201 ATAACTACAT TGATGAGGTG ATGCTTGGAT GAGATTAAGT GACAAAATTA TTATGACTTC 13261 CTTTTTACTG TTATTAATTG TTTCAGTCGT CTTATCAATA GTTACGGGAA GTAAAGTCTG 13321 GATATGGATT TTTCTTTTTC TGATGACACT TGAGATGCTT TACAAAATT GGCGTTAGGA 13381 GCGTGACTAA TGAAAGCAAG ATGTGGCGAT TGGAGTACTG ATGTTTATCC AGTTGAACCG 13441 TTTGTTTATG AAGTAGCAGC TGATGGTAAG AAAGAATTTT ATCAATCAGC ATGGGATGCT 13501 TTTAGTTCTG AATTGCATAT GAAAAATGTG ACGGCGAAGA TTATCAAAAT ACCAGTTGTT 13561 CCAATGAGTA ATGATGAAAT TAAAGCAGAG AGTGTTGCAT TTGAATTAGG CGAAAAAAGG 13621 HELPCCAC ATGTGGAAGA ATTCACTAAT AGTAAACCGA GGAGGAGT ATCATTTCTT 13681 CAGGTTGCGG AAGCTTTTGC AATTATAACG TGGATTATTT TAATAATTCT TATAATAAGT 13741 ACGGCGTTTA TGTAGGAGGT AAGTTACTAA TGACATTTGA AGAGGCGTTA AAACATGAAG 13801 AAAATAATGT GCCAGTATTC TATAGCGATC GAAAATATTA TGTAATCGGG CACAATGAGT 13861 TAACCGAACA ATTTACAATT CGTGAGCTAA GTGGTAATCC GTTATTTACG GTGCCGGTTG 13921 ATGTACAAGC GGAGGAATTG TCATGAGTAT TAAAATTAAT GCGCAAACAG TTGTATTTAA 13981 GGGAAGT TTTATTCCTA GCAAAAGTAA CTGTGAGTAT TGTCAATTTTC HELP 14041 GTTAATGGTT ACTAAAGCAT CTCCAGATCC ACCAGATAG ACTAAAGCAT 14101 TGACGGTGAG GTATTTAATT ATTGTCCTCA TTGTGGACGG AATTTACAAG GGTGAGGCAA 14161 TGTTACTTTT AATTGTATTA ATGATGATTG TCTTTATTGC TGGGTTCCTA TTGGGTAAGA 14221 AAAATCCATG ACGAAAAAAG GACCCACCGT AAAAGATGTG TCCTCACTAA AAATATTAA 14281 CCATAATTAT TATATCAGAT AGCGAGGTA CGTCATGCAA ACAAGTTTGA ATTTAGAT 14341 TGATTGTCTG AAAACTGCAA GAAAGGTTAC TGACTTTCTT GATAAGAAGC TGGATCGCTA 14401 TCTGGCTTTA TCGGGGAAGC AACGTTTTGA TTTGAAGTCA CCAGGGATGG ACGGAATGCC 14461 TAAAGCTCCC AGCCATGGTA ACGGTAGTGA AAATCGAATG CTGAATATCT GGTTGGCAGA 14521 AGAGGTTGTT GATTGTGTGG GTTGCGCTAT GCGGAATG ACAAAGGAAT CACAACGGAT 14581 TTTACTAAAT CGGTATTCGG ATCAGATGTT AACGTATAAC ATTGCTAGGG AGCTAAGTAT 14641 TAGTTCAGCA ACGTATAGTC GAAAGCAGGA AAAAGCGCTG TGTGAGTTTG CGGACCGGTT 14701 TGAATTTCAG TTAGTTAAGC ACGGTATTCA TACTGAAATT GATGATCTAC ACGTTTATCT 14761 TGACGAGGAA GATTGATAAA TTGATGATAG ATTATTGAGC GAGCAATTCA TGATAGAAAT 14821 GTGATAATAG TATTGTCGAA TGATTCGATA TTCATATAAT AATCTTCCCA AATGAAGTCT 14881 AGCTATTATG GCTAGGCTTT TGTATTATGT TTAATTGGGT GATTTTTATA TGATTGAATA 14941 CTTAAAAACA TTTTTGGAGG CTTTGAGTAT GAAGCCAAAA ACTAAATTTG TTGGAGTTAT 15001 TTTTGGAATA GTACTTTTAT GCTTAAAACC ATTTTTAATT CAATATAATA TGAAATGGTTT 15061 TTACAATAAG TTTTCTTGGA TTATTATTTT AATTACTTTA TTTTTTGTAG CCTCATTAAT 15121 AATTGAAGTA ATAGTTGAAG TATACGAATG GGGTAGAAAC AAGTATAACA AACATAAAGT 15181 TGAAAGAGAT TACGAAAAAT ATATCTTAGG CTTGTCTGAT AAAAAGTTGG CAATTGTAAA 15241 GAAACTTTAC GCTAATGAAC ATCACCAAGG ATATTTAAGA CAAAACGATA CTAATGTTAT 15301 TGAATTGGTT AATATGTACG TAATTATGCA ACTTAATAAT GAAATTTAG TAAGAGAAAG 15361 CCAAGTTGAA GATATAAACG ATCCTGAATT TCTTTTTGTA TTACAGCCAC CGGCTTTAC 15421 CATCATAGAA AAGAATTCAG AAAAATTTAA ATAAATTTAA TTAGTTTAGC TTAACGGCTG 15481 ACTTTTTACT TTTTAGGAGG TGAGTAGCAT TACTCAAAAA TTAACACAGA AGCAACAACG 15541 ATTTGTCGAT GAGTACATTA TTTCGGGTAA TGCTACTCAG GCGGCAATTA AAGCTGGATA 15601 TTCTAAGAAG ACAGCTAAGC AGTCTGGTGC TGAAAACCTA GCAAAACCTT ACTTAAAAGC 15661 TGCAATCGAA AAACGCAATG CTGAAATTCA ATCCGAGAAA ACAGCTGATA TGACAGAGGT 15721 GATGGAATAT CTTACTTCAG TTATGCGTGG TGAGCAAACA GAATCGGTTG CTACTGCTAA 15781 GGGTATTTAT GAAGACGTTG AAGTGTCGGC AAAAGATCGT ATTAAAGCTG CTGAATTAAT 15841 TGGAAAGCGT CACGGCGCCT GGACTGATAA AAAGGTTATT TCTGGTGATG TTCAGATTGA 15901 TGTGGGAATG GGGGATTATG ATGATGAAGA GTGAAGAACA ATGGAGAAAA ATCAAAGATC 15961 ATCCTCATTA CTTGGTTAGC AATAAAGGTA ATGTTTACAG TGAGTATAAA GGCGGCTTGC 16021 TTAAACAGAT GAAAGATGCT TATGGATATT CTCAGGTTAA TTTAAACCGC CGCTCCAAAA 16081 AGGTGCATCG TTTAGTAGCG GAAGCTTTTA TCCCAAACCC AGACAAATTG CCTGAAGTTA 16141 ATCATAAAGA CGAAGATAAA AATAATAACC AGGTGGATAA CTTGGAATGG TGTACTAGCA 16201 AGTACAACAT GAATTATGGT GACGTGGAGA AAAGGTCAAT TCTTTCACAA CAAAGCCATA 16261 GTACTTGGAA AATTTATCAA TATGATTTAA ACGGTAATTT GGTAAAAGTA TGGAATTCAG 16321 CGAGAGAAGC CGACAGACAT GGATTCAACC GTAGAAGTGT GTATCGCTGT TGTGATGGGG 16381 AAATAAAATC TTTCAAAGGA TACATATGGT CAAGACAAAA GAAGGTGATA CCATGCCAAA 16441 CATCAAACTA AATTTTCTA AACCATACAA CGTTTTCAAT AAACAAATTT TTGATAACTT 16501 GTTTGATTAC AGTCATTTCG TTGAGGTTTG GTACTGACTT ATGGCGGTGC ATCTTCTGGT 16561 AAATCGCATG GTGTGGTACA GAAAGTTGTA CTTAAATCAC TCCAACACTG GAAACATCCC 16621 CGCAAAGTGC TATGGCTGCG GAAAGTTGAT CGAACAATTC AAGAATCTAT CTTCGCTGAC 16681 GTAATTGACT GTTTATCAAA TTGGCAATTG TTATCGTTAT GTAGAGTAAA TAAATCAAAC 16741 CGTACTGTTC ATTTACCGAA CGGTGCGGTT TTCCTGTTTA AGGGTATGGA TGACCCAGAA 16801 AAGATTAAGT CAATCAAAGG GTTATCTGAT GTGGTAATGG AAGAAGCTTC CGAATTTCA 16861 CAGGACGACT TCACGCAGCT TACCCTACGT CTCCGTGAAC CTAAGCATAA GAAACGACAA 16921 TTGTTTTGTA TGTTTAATCC AGTTAGCAAA TTGAACTGGA CTTATAAGCA ATGGTTTGAT 16981 CCGAAAGTGA AAGTTAATCC GGAACGAGTA TCAATTCACC AATCAACTTA CAAGGATAAT 17041 CACTTTTTGG ACGCTGATAA CATTGCAACG ATTGAGAACT TAAAACAAAC CAACCCGGCC 17101 TACTATAAAA TCTATACGCT GGGCGAGTTT GCTACATTGG ATAAGCTGGT CTTTCCAGAG 17161 TTTGAAAAAC GTCGGTTAAG TATTCGAACC TTATCACAGC TTCCCTCGTA CTTCGGCTTG 17221 GACTTTGGGT ACACTAACGA TGAAACAGCC TTTATGCACG TTAAAGTGGA TGAGAGTACC 17281 CGTAAAATTT ACGTGATGGA AGAGTACGCT AAGCACGGTA TGTTGAACGA TGATATTGCC 17341 CGAATAATTA AACAAATGGG TTATAGCAAG GAAGTTATTA CTGCTGATGC TGCTGAGCCT 17401 AAATCGATTG CTGAAATTAA ACGCGATGGT ATCTCGCGGA TTCGTCCAGC TAAAAAGGGG 17461 AAGGACAGCA TTATACAGGG ACTTTCATTT ATGCAGCAAT ATCACTTAGT CGTTGATGAC 17521 CGGTGTGTGA AAACGATTGA GGAATTGGAA AATTATACAT ACAAGAAGGA CAAACAAACT 17581 GGTGAATACA CCAATGAGCC TGTCGATAGT TACAACCACG AAATCGATGC TATCAGGTAT 17641 GCTTTATCTG AAATCAACGG AATGGCTAGT CCAAAGGCAA CTGTAATGAA AAATATTTAT 17701 ATTTAGGTGG TGATTGAATG GAAACAGTAA ACGGTAAAGG ACAAATTTTA GATGGCCATA 17761 TTTTTATCTA TCCAGCTGAT GAAGAAGAAC TTGATCCGCA TGATTTACTG TCGTTCATGA 17821 GAAGAAATAT TCAGTATGCT AAGGATTACA AGCATAATAT GCAAATGTAT CTAGGTAATC 17881 ACGATATCTT AGATCAACAG CGGCGGATGT ATGGGCCAGA TAATCGGCTA GTAGCAAATT 17941 TACCGCATTA TATTGTTGAT ACTTATAATG GATTCTTTAC TGGAATCCCA CCTAAGATTA 18001 CTTTAGATGA TAAGAATGAG AACGAAGCAT TACAGCAATG GAATGACACT AATTCGTTCC 18061 AGGACAAATT GAGTGAAATT AGTAAGCAAA CGGATATCTA CGGACGTTCG TTTGCTTTTA 18121 TTTATCAAGA TGAGAACGCA GACACTTGTA TTGCTTATGC TTCTCCTACA GATGCCTTCA 18181 TGGTTTACGA TGATACGGTT GCTAGAAAAAC CTTTTGCTTT TGTTCGTTAC TGGAAAGATA 18241 CTGAAAGCGG ATTATGGACC GGAATGGTTT ATTACGCTAA TAAAATTAAA ACCTTTAAAG 18301 GTAGTGTTGT TGAAGATTCA GATCAAAATA ATATGTATAA TTTAGTGCCA GCAGTTGAAT 18361 TTTATGGAAA TGAAGGCGG CAAGGTGTTT TTGATAATGT GAAAACCTTA ATCGACGAAT 18421 TAGACAGAGT GTTATCACAG AAAGCTAACC AAGTGGAATA TTTTGATAAT GCTTACCTTA 18481 AAATTCTTGG TCTTGATTTA GATGAGGATG GTGATGGTAG ACCGGATGCT AATTTAATTG 18541 GTAATCAAAT GATTTATTCG CCTAATGCTG ATGCTGCTAA TGCCGATGTC GAATTCATTT 18601 CAAAACCAGA TGGTGATAAT ATGCAAGAAC ATATTATTGA CCGGCTTGTT TCAATGATTT 18661 ACCAGGTAAG TATGGTTGCT AACCTTAATG ATGAAGCGTT TGCTGGTAAT AGTTCTGGGG 18721 TGGCTTTGCA ATATAAGTTA CTTCCAATGC GAAATATGGC AGCTAATAAA GAGCGTAAAT 18781 TTACTCAGGC ACTCCGGAAG TTATATCGAA TAGTGTTTAG TGCTGATCAA GTAGTCAAAG 18841 ATAAGGAAGC CTGGCAAGAC TTGCTCTTTG ATTTCAAACA AAACTTACCG ATTGATGTTT 18901 CTGAAGAAGC TGATACTTTA CAAAAACTAT CAGGGGTTGT GTCAAAAGAA ACTGCATTCC 18961 GAAATAGTCG TTTAATTGAT GATCCTAAA AAGAAGTTGA GCGTATGCAA AAAGAGAAGC 19021 AGGAAGAAAT AAACCAAGCG CTTCAACATT CTGCTTCTGC TACAGATCAA ATGCTAATGG 19081 ATGATCAAAA AGAAAATGAT AAAGAGATAG TTGGTTTCCG GAAGAACGGT GAATCCGATG 19141 ACGAAGAAGA ATAATTATTG GGCTGATCGT ATTGCTCGGG AACGTAAATG GCAAGAAGAG 19201 CAATTAAGTA AAGATGCTCA ATTTAATCAG CGCCTTCAAC AGTATTATGA TCAAGCAATT 19261 GTCCAGATTA TAAAAGACAT TGAAGATCAG ATAAATTCTT TAGCTGTCCG GAATAAAGTT 19321 TCTTATGCTG AAGCTCAAAA AGAAGTGTCC ACTACCGATA TTGCTGATTA TGAAACAGAA 19381 GCTAAGAAGG TAGTTCAGGA AGCTAATCGT TTAAGAGCAC AAGGGAAGCA TGTTACTTAC 19441 AATGATTTCT CTGATGAAGT TAATGAACGA TTGAGGAATT FATHERCGGC GATGCGATAT 19501 AACCGATTGA ATTATTGA ATCTAAAATT GGTTTATCGA TGGTTGAAGC CGGAATGAAT 19561 ATTGATGCTG ATATGCAAGC TAAAATTGGT AAAGATTATA CTGATGAGCT AAAACGTCAG 19621 TCTGGTATTC TAGATCATTC TACCGAAAAT AGTTCGTTTT GGACTTCTAA AGATGTTGCG 19681 AAACAAGTAA TGAAGCAAAT TAATGGAGCA ACTTTTAGTC AACGAATTTG GGCTAATCAA 19741 GATACTTTGA AAGCTCAACT TGATACGGTT ATCACCAACG GAATTTTAAC TGGTAAGAAT 19801 CCGCGAGTTG TAGCAAGACA ATTAAGAGAT AAAGTAAAAG TCACTGTTAA AAATCACAGT 19861 TATGTTACTG AACGTATTGC CAGGACAGAA TCAGCACGGG TTCAGTATTC TGCTCAGATT 19921 GAATTAATCA AAAAGAATGG TTATCAATTT GTCCACTGGA TTGCGGAGCC AAGAGCCTGT 19981 GATGAGTGTC GAAAGATTGC GACGCAAGAT AATGGCTTTG GTGATGGTAT TTATCGAATT 20041 AATAAAGTTC CTAAAATACC AGACGATACT CATCCTAATT GTCGCTGTTC AATTAGTGAG 20101 ACATGGGTCG ATGGTCAACG CAATATAGCA TTATCTGATG ATGAACAGGC GGCATTGAAT 20161 AATTATATTA GTTCAGATTC ATATAAGATT AATGATGATT TGAGGCGTAA TAAGATTTCT 20221 AAAAAATAAGA AACAATTTAT TGAAAACTTA GATGCCGCAT TGGCTAAAAT GCCAATTTAT 20281 CATAGTAGCA AGCCACTCCA GCGTGATTAT TTCTTTGATA AACAAGAAGC ATTGGATGAT 20341 TTTATTAGTA ATTTTGAAAT TGGTGGAGTC TTCACTGATT CATCATACAT TTCAACTTCT 20401 AAAATTTATT ATGGACAGGG CAAAGAGACA ATTCATGTTA TTATTAATC AAGTAAGACA 20461 GGAAGAGATA TCTCTGAGTT TAATTTTAAT GAGCAGGAAG TATTATTCCC CAGAAATAGT 20521 AAGTTTAGGA TTGATGATGC ATACGTTGAT GATAACGGGA AGATGACAAT GGTTTGGAGT 20581 GAATTAGATG AGTAACAAGC CTTTTACTGA TAAACGTTGG CGAGATAATT CTTTGGAAGG 20641 CGTTAAATTT GATAATTCAA AAGTAACGTC AGAACAAAAG AAGAAGACAG AAGAATTCCA 20701 TGAGTTATTC AAAAAGACGT TTGCTAAACA ATTAAAAGAA AAACACTCAC ATAAAAAGTA 20761 GGTGATCCAA TGGGAAATAA TGATTTCTTT ACGGTAACGT ACAAAATACT AAGTTATCTT 20821 AAGTATTGTT ATGAAAATGG AATTAATCCT GATCCTAATA TTCTTAATGC TGATACATTT 20881 AATATTAGTA AAGTTCAATT TGGAAGAACT CTACAAATGT TAAGCGAGCA TGGTTATATT 20941 TCAGGAGTGA GATTTACACA AGCCAAAATC GAAGGTACTG TTGTTGGTGG ACTCCACAAT 21001 ACGTCAATAA CGGTTGAAGG TCTGCAATAT TTAGCTGAAA ACTCAATGAT GAAAAAAGCA 21061 TATCGAATTT TTAAAGAAGT CAGAGATTGG CTTCCGGGTT TCTAAGCATT CACAAATTAG 21121 TGAGTGCTTT TTGTTTTGGA CTTTTTACTT GTTGCAGTCG TTAAAGAACA ACCCGGATAT 21181 TACAGTCCAC CGGACTATAA ACGAGGTGTA TTTATGTTTG AAAAATTACC AATGCGTTTA 21241 CAATTCTTTG CTGAAGATCC AACGCCAGAT CCAGATAATG ATGGTGCACC TGAAGGAACT 21301 ATTACKGGAG ATAACGGTAA ATTACKGAAAAG ACATTTACTC ATTACKGTATT AAACATTATT 21361 GTCAAAGCCC GAGTCAATCG AGCCTTGAAG AATAAGCAAG AGGAAATTGA CCAGGCTAAG 21421 REPEAT CTAAACTTGC SERIES AGATCAAAA SERIES TAAGCTTCAA 21481 CAAACTGAAA AACGTGCCCA AGATGCTGAA GCAGAATTGG CCCGTTATAA AATGCGTGAT 21541 ACAGCGAAGC AACAATTAAT TGATGGCGGT TATGACAATC CAACTGATGA AGATATCGAT 21601 TTAATTGTTA CTGATAAAGC AGAAACAACT AAAGAACGTG GTGAAGCATT TCTTAAAGCT 21661 TATAACCCAA TTAAAAAAA TGTTCGTCAA CONCLUSION AGGGAAAAGTC ACCACGAATT 21721 AATGGTGCTC CTGCTACTGC AATGACTAAA GAACAAATTG CAAAGATCAA GGATCCCCGTC 21781 AACGGGTCC AAGCCATTCG GGATACTTA TCCCAATG AAAAAAAAAA GGAGGAATAT 21841 AAAATGGCTG AAACTAATTT AACGAAGT ACAGACCTAG TTGCACAATC TATCGACTTT 21901 GTAGAACAAT TCTCTGGAGG AATCCAAACT TTATTGAATG CATTGGGAGT TATTCGTATG 21961 CAGCCAATGA CTACTGGTTC ACAGATTAAG ATTTACAAGT CAGAAGTAAC TAAGGTCGAT 22021 GGTAATGTTG CTGAAGGGGA AGTTATTCCG TTAAGTAAGG TTACTCGCAA GCTAGCTAAT 22081 ACTTTGACAT TAGGATTTAA AAAGTATCGT AAGGTAACTA CCATTGAAGC TATTCAGTCA 22141 GCTGGTGGTG CTACACCTGC TATCGTGGAT ACTGATAATA AGCTACTTCG AGAAATTCAA 22201 AAGGATGTTA AGAAGGACTT ATTTAATTAC ATTACCAAGT CTGATGCAAA CAAGACTACC 22261 GCCTCTGGTG ACGATTTTCA AAAGGCAATG GCGGCAGCTT TAGGACAACT TTCAGTTAAG 22321 TGGGAAGACT ACGACACACA AACTGTCGCC TTTGCTAATC CGCTTGATCT ATATGCATGG 22381 TTAGGTAACC AAACTCTTAC TGTTCAATCT GCCTTTGGTT TGCAATACAT TCAGAATTTC 22441 CTTGGCTTTG ACACTATTAT TCTAAGTGCT GAAGTACCAC AGGGAACGAT TGCTACAACA 22501 GTTGCAGATA ATATCAATTA CTTCTACGCT CCAATTTCAT CCGTTGGTCA GTTATTTAAC 22561 ATGACTTCTG ATGAAACTGG TTTAATTGGT GTAACTCATG ATGCAGTTAA TAACAATTTG 22621 TCATACGAAA CTGTTGTAAC AATGGCTAAT GTATTGACTA CAGAACGTTT GGACGGCATT 22681 GTATTGTCAA CAATCAGTGG TGCTAAGTCT GCTGGTAAGT AGGTGATTGA ATGGACCAGA 22741 ATACGGTTTT GCAAAACTTA AAAGTAATGC TTGAAATTAA AAATGATGAC CGTGATGCTT 22801 TGCTGAAACT AATCATTGAT AATACAGACC AAGCATTGCG ATTTAAGCTA GAACTAACTG 22861 AAGACGAAAA TTTACCTGGA GAACTAGGTT ATATTGAATT AGAAGTTTCA GTTCGACGAT 22921 TCAATCGACT GCAAAACGAA GGGATGAGTC AATATAGTCA AGAAGGGGAA AGTATTACTT 22981 TTAATTCTTC AGATTTTGAT GATTTCCTTG ATGATATTGA TTTGTGGAAA CGACGACACC 23041 AGAAAGATGT TAAATCTTTA GGTGCCGTTT CTTTTATTAA TCCTTATGCG GGGATGAGTA 23101 AAAATGCGAA AAACACAGAT AATTAAGTTT TATTTTCAAG ATGAAAATGG CTATAATCCA 23161 TATGCAGAAG AAGACACGAT TACTAGTCCT AAGCTAGTAG CACAACGGTA TGCCAATGTT 23221 ACTGATGTAG GGACAAATCG CCTAGTTGAA TTATTTAGCA GGCTAGATCA GAACGCCAAG 23281 GTAATTCGAT TGGAGTCTCC AGTAAATGAC TCTTGGTCAT ATCTGACTAT TGATGATTGT 23341 CCTATCAAGT ATCGTCTTGA AACCTGTCGG AAACCATTAA AAGGCACAAC GCTGATTGTA 23401 GGTGAAGCCA GTGGCTAATT CTTTTAAGGT TGATGTTAAA GGTACTAAAG AACTAGCGAA 23461 TTTCTTAAAG AAGAATAAAG ATTTGACTCC AGTTAAACGG ATAGTCGCAA AACATGGAGC 23521 AGGTCTCAAA AAGCAAACGC AGCAAAATAT GAACAATTTG TATAAGGGCC ACTACGAATG 23581 GAAGAAGGGG GCTGGGCTAA CAATGGTTAG CCCTACCGGG AATACTAGAC GGTCCGTAAC 23641 AAATACAATT TCTAATAATG GTTTAACAGC AACGGTTGCT CCACAAACTG AATATTTCCC 23701 ATATCTTGAA TATGGAACTC GCTTTATGGC AGCACGACCG ACATTACATC CAGCGTTTGC 23761 AATTGAGTCT ATGAAATTTG CTAATGATTT GAATAAGTTA TTTAAGTAGG TGAGAAAATG 23821 TCACCAAGTA TTGAAATTTA TGATGCAGTT TTTGCTCAGG TCCAAAAGCA TTATCAGACC 23881 TACGATCACCC CACCGCAGTT AAATGAACCA GTTACCTATC CATTCGTGGT TGTTGATGAT 23941 AGCCAGTCGA TTTTGACGAA CTATAAAACA GCCACAGGAA TGCGGGTAAC TTTAATAGTC 24001 CATGTGTGGG GGAAGTCTAA CCAACGTAAG ACTGTACTA AGATGGTTGA TGAAATTAGT 24061 CGTCTGGGGA TGCAAGCAGT TCGGACGAAA CATTATGCTT GGCAAGGACG ACCTAATGAG 24121 STORM ATTACK TGATACGAGT GTTCCGATA CTGTGTTAAA GCACGGTTAT 24181 TTAACACTCG TTTTTGATTT GAAATAAAGG AGGATAAATA TGGCAACATA TCCAGTATTG 24241 GAAGGGAAGA ATGCAGTTCT TTTTGAACGA CTATTAGAAA ATGCAAGGAA AGAGCCGGCA 24301 CAATTGATCC CGTATCAAAC ATCACTAAGT TATGATCCTA AACGGGATAC TGATTCAACA 24361 ACTACGAAGA TGGGGAATGT TCCTACTGCT TCTAATATTG AAACAGATTT AGAAGTAGAG 24421 TTCCTAAATG HELPTTCCAA AGCTGCAGAT GATGTTTATG ATTCTTTGTA CTTTAATAAG 24481 AAGATTGAAG TATGGAAGGT TCATATTGAT CGAGTCCGGT CAGATGGCAA AGTTTATGCC 24541 GAATATATGC AAGGAATTGT GTCAGAGAC TCTAATGATA ACGACCCAGA CGATCATTCA 24601 ACTCGGGATG TGACCTTTAC GATTGATGGC GTGGCCAAAC GTGGGTGGGT CACTCTACCG 24661 CCAGAAATCA AGGAAGAAAT TGACTATGTA TTCCGTGGCT TGGCACAGCT TAAAGGCGAT 24721 GACGACAACG GTGAAGGTGA AGCTTTTGCT GATGGCGATC GTGGTGCTGG TGCAAATGAA 24781 GCAGTAACAA CTGAATAGGA GGAAGATTAT GAAGTTAAAA ATTAATGGTC AAGACCAATC 24841 ATTTGTATTC GGAGTTAAGT TTTTGCGAAA ACTTGATGCT TATCGGGGCG CTGAACAAGA 24901 AATCCAAGGA GTTAAGGTTA AGCTAGGAAT GGGGCTAGCC ATGATGCTTC CCCAATTAAT 24961 GACTAAGGAT GCGGCCGCTT TGGCAGACGT GTTGTACTGT GCGGCTAAGT CTAGCATTAA 25021 GTTAGATACA ATTGATGATT ATATTGATAA TTGCAAGGAC TTGGATTCAT TATTTAATCG 25081 GGTAATGAAT GAAATTAAGG CAAGTAATGC CGCTAAGCCG ATTGCAAAAA ATCTAAAAGC 25141 CTAGATGGTC CTGAGCTTAG TTCAGAACAA AGCTATCACG AAATTCTTTT GAATTCGTTG 25201 GCTTATCTAG GCTTTCATAA TATTTCAGAA ATTGAAGAAA TGGGATTGGC TGAATATCAG 25261 CTCCGGATGG AAGCCTATAA CCTCCAACGG GTTAGCCAGG AACGAGACTT AGCATTGCAA 25321 GCTTTCCTTA ATCAGTCGGT AACAAGCGACG AAAGGGAGCG AAAAGCACCC AATTCGAAG 25381 TATAAGAAGT TTAGCCAATT TTTTGATTAT GATAAATTTG TTGATGATGT TCGTGGGCAC 25441 TATGAGCCTG ACTATCAGCC AACAAGCAAG GCCAGCCTTG AAAAGAAACG AAATGATCTA 25501 ATCGTCAAGC GGTGGCGTGA ATTCCGGAAG ATGAAACAAA AACAGAGAGG AGGTAATGGC 25561 TAGTGTCACA ATCAATGAGA GTTGAAGCGG TATTATCAGC ATACGATGAG AGTTTTAGCG 25621 CAACCTTAGA TAAGGCGCTT AAATCGATTA ATAATTTAGG CCGTGAAACC CAGTCAACCT 25681 CTCAAACTGT TAGTGCAGGT GGTTCTAGTA TTTCCAGTAC CTTTAAATCG ATGGCTGGAG 25741 CAATGGGTGT AGTTGCGATT GCTGGTAAAG CATGGGACGT TGTTAAAGAT TCAATGAGTG 25801 GCGCCATTAA CCGGTTTGAT ACATTAAACA AGTATCCGGT AGTAATGAAG GCTTTGAATT 25861 ATTCAACTAA GGATGTTGCA AAGTCAACCG CTATCTTATC TAAGGGAATT GATGGATTAC 25921 CTACTTCTTT GCAAGACGTT ACAAGTGTTG CCCAACAATT AGCGCCATTA ACTGGTAGTG 25981 CAACTAAGGC TTCTAAGTCG GCGATTGCCT TGAATAATGC CTTCCTTGCC TCCGGTGCTA 26041 GTGTTGCCGA TACCTCTCGT GGACTTCAAC AATACACACA AATGCTTTCA ACTGGTAAAG 26101 TCGATTTAAT GTCTTATCGA ACATTGATGG AAACCATGCC AATTGCATTA CGTAAAGTCG 26161 CCAATTCATT TGGTTTTACT GGTAAGTCTG CTGAACAAGA CCTTTATAAA GCTTTGCAGT 26221 CAGGACAAAT TACGGTAGAT CAGTTGAATG ATCGTTTTAT CAAGCTGAAT GGTGGAGTTA 26281 ATGGTTTTGC TCAATTAGCA AAGAAAAATA GTGAAGGTAT CGGTACATCT TTTGCAAACT 26341 TAAAAAATGC CGTTGTCAAA AATCTGGCAA ATATGTTATC GGCAATTGAC AATGGTTTTA 26401 AGCAAGCGGG CTTTGGAAGT ATTGCACAAG TCCTAGACAA CATGAAGGGT AGTATTAATT 26461 CTGCTTTTCA AGTTATTGGA CCAGTTGTTA CTAATGCTAC TGTTGTAGTT CTTAATTTTG 26521 CAAAGGTTAT AGGCGGAGCG CTTAAATCTG CTTTCAGTAA TGATATTTT AAAAACAGCAG 26581 TTGTGGGAAT ATTAGGCTTT GTGGGTGCAG TTATGGCAGC CCATAAGGTT ATTTCAATAT 26641 TTACAACATT AAGATCTGCA ATAGTTGGTT TAAGTGTGAT TACAAAAGCT GGTAATTTGG 26701 CAATGGCGTT TAGTGAAGCA ATGTCAACAC TTGCTAAAAC TTCTAAGATT GCTGGTGGAG 26761 CGATGAAAGC ATTCAGTGCG GTGGCCTCAT TAGGTCCCTG GGGAATTATT GCTGTTGCAA 26821 TTGCAGCTGT GGTTGCAGCC TTAACTTATT TCTTTACCCA AACGAAAACC GGTAGGGCTT 26881 TATGGCAAAG TTTTACTACG TGGTTATCTG GAGTATGGCA GAGTTTGGTT GGAGTGGCTA 26941 CTACTGTTTG GAATGCAATT GGTAATGCTA TTAATGCAGT AGTTAATTTT ATTAAACCTT 27001 ATTGGCAAGG ATTATTAACA TTCTTTACCG GAATCTGGAC ATCAATTGTG GCGGGTGTTG 27061 CTCCAATTTG GCAAGGGTTA GTTAATGTCT TTAATAGCAT TATCAGTGCA ATTTTAGCCG 27121 TTTGGCAGGC TTTAGCTCCA ATTATTGTTC CGATTGTAGC TGGTGTAGTT GCTATCATTG 27181 GGGCAACCCT AATTACGATT GTTACCGTCT TTCAAACTGT GTGTAATATG CTTGTACCCA 27241 TTGTTCAAGT TGTATGGCAA TTAATTTCAA CAGTTGTATC TACTGCTATT ACGATGCTAG 27301 GTACAATAAT CCAAACAGGC TTGGCAATTA TCGTTGCTAT TTGGAATGTG GTCTGGAATA 27361 CATTCAGTAT TGTTGTAAGT ACGGTATGGA ACGTTATTAC TACTATTATA TCTACCGTGC 27421 TGAACGTTAT TGCGGGAATA ATTCAAGCTA TCACTGCTGC AATACAAGGC GATTGGTCAG 27481 GAGCTTGGAA TGCAATTCAG AATGTTGTAT CAACTGTTTG GAATGCAATT GCCAGTATTA 27541 CTTCTAGTGT ATTGAATGGA ATAAAAGGAA TCTTTGATGG TGTAATGAAT GGTTTAAAGA 27601 GTATTACTTC TAGTAGTTGG AATGGTATTA AATCCCTATT CAGTGAAGGT GTTAATTTCA 27661 TTAAATCAGT TGTTCATATA GATTTAGGTG CTGCTGGTAG AGCTATCATG AATTCACTTT 27721 GGAATGGAAT GAAATCCATT TGGAATTA TTAAGAATTG GGTTAGCGGT ATTGCTGATT 27781 ERROR ERROR ERROR CCAGCTAGTT ERROR GTTACTTATT CCAGCTGGGC 27841 AAGCATTAT GAATGGTCTT AATAACGGAT TGATTAATGG ATTCAGTGAA GTTCAATCAA 27901 ACGTTAGTGA TATGGCTAAT CAAATTCAGC AAGCTATTAC TAATCCAGGC TTTGATATTG 27961 STEP TGGTAACTTG GGTTCAATTA ATTCAAATTA TACTGGTAGC CTGGCAATTC 28021 CONNECT GTTACAAATG CONNECT CTTTGCTTCG TCAATTACTT CONNECT 28081 CGACAATGGT TCTTGACGAT GGCACTCTTG TTGGCTATAC AGCGGATCAA TACGATTATC 28141 GCTTGGGTCA AAATACAGCA TTGAAGGATA GGTGGAGCCG ATGAAATTCT TAAATAATGA 28201 CTATTCTTTT CGTGGATTAG GACCCACAAA GGATGATCCA GAATACTTAG AAAATGCAGA 28261 ATATATCGAC TTTGCCGGTT TTAATTCTTC TGATTATGAT TGGTGGTTGA TTGATCGAAC 28321 AGCAACTACG CCAGAAGAAC AAGAAATTAC AGAAAGCGTC CCTTACATGC AAGGAGAATA 28381 TGATTTCTCA ATGTATGATC AGGAACGTTT TTTTAAGACC CGTGAGTTGA CTTATAAGTT 28441 TGTATATTTT GGTGAAGTT ATCAGGATCG TAAAGCTTAC GAAGAGGAGC TTAAACGGCA 28501 ATTACTGCCA CATGGTTTCCA CTAAACTAAT TGATTCTCAT GATCCTGTTT ACTACTGGTC 28561 AGCTAAGTGT ACTAGTGTTG AGGTTGAGGA TGACCAAGAA AAGGGAATGC TCACAGCAAC 28621 TATTACTTTC AAGGCTTATC CTTTTGCTTA TACTAATCAT AACGAGGGCA CCGATTATTG 28681 GGATGATGTC GCATTTGATC ATTGGATTTG GCAACCAGTT AAATTCAATG TTAACGGTGA 28741 TCAGGATGTT AATGTTAAGA ATATCGGCTC ACGACCAGTC GAATGCTCAT TTCAATTGAC 28801 AGGGGCCATA ACTTTGAAGA ACGATTCAAT TGGTGAAGTA GGTTTAACTC AAGACAATTT 28861 TAAAACAACC ACGATTGTAT TAGAGATGGG TGACAATAA ATGCATCTAT CCGGAAACGG 28921 CONFLICT TTTCAATTTA AGCGTGAGGA CONCLUSION TGTACCGAAT TATTGGTTAT 28981 AATGAACCA SECTIONAAGC NATIONAL GTACTGGATC CCCGAGTTATT TCGTCATATT 29041 AGTTCGGGAA AACTCACGCT TAAAGAATCT AATATTGATG ATTTGACTAT TACGGTTAAT 29101 CAAGCAAGTC ASSISTANCE CAACGTAAGG CCTTATCATA CTCATGTTAA CGTTTATGAT 29161 GATAATGAAC TTATTTTTCG TGGACGAGCT ATCAAACCTA AAAAGTCGAT GGAAGAAAGC 29221 GGACAATTCA TTCGTGAATA TGTTTTTGAA GATATTGAAG CATATCTCAT GGATAGCACC 29281 CHAATTTT ATGAAGGTGT TGGTCAAACG CCCAAAGAAT TTTTACAAAAC TTTAATCGAT 29341 GTTCATAATT CACAGGTTCC TGACTATAAA AAGTTTCAAG TCCGGAATGT AAATGTCACT 29401 AATAATAAGG ATTACK TCGAAATT ATTACKCCCA AAACTAGCGA TGCTATTAG 29461 GATAAATTAG TTAAATCTCT TGGTGGTTAT ATTGTGACTA CTTACAACGC TAACGGAATA 29521 AACTACATTG ACTACTTAAC GGATATTGGG GTTGATCATA AAGATGATAC TCCTATTCAG 29581 TTAGCTAAAAA ATATGAAGTC TGCAAGTATG CAAATTGATC CTACTAAGGT GATTAHAAGA 29641 CTGATTCCAC TGGGAAAGAC ACTAGAACCA TCAAAAGTTG ATGTAAGTGA TGATGATGGA 29701 GAGGGCGTT CTGGATCATT AGATAGCCCT GAAGAATTTT GTAAATCAGA AATTAATGCT 29761 ACTTGGGGTA GTGATTAA TATATTGAAA STARTTTG CCGCTCGTTC TTCGAGAGTT 29821 CGGGCTTGGG GAGTGGACGT TAATCGTTTA TATGATGTGG TGAAAAATGC TGGAGTAAGT 29881 CCTGAATGGT TCTTTGCTTA TGAACTTCAA GAAGAAGGAA CTTACTATGG ATGGCTTAAC 29941 CATACTTATC GACACGGTGA TGCGTATAGT GATGCGCAAT CTGTTTGTGA GTGGATTAAA 30001 AATTGTTCAA ATAGTAATTC CATTAATCCA GCATGGAGCG CACCGGAAGG ATCAATGGCG 30061 CCGAATCAAG HELPCGGA TAAATGGAAT CATTAGTTG GAAAAGGTAC TATTGGCCGC 30121 GTTTATTTAC AAGGGACTGC CGCTGCTGTT TGGGATTTAG CTGGTCAAAC GCCTAATCCA 30181 GCTATTGGAA AGCCAATTAG TGGATGCATT TCTTGTATTA AACGTTGGGG TGGTCATTCT 30241 AATGCAGCTG GTGGTACATG GGGATGGCCT TTTCCTGATG TTGGGGAAGG TCATTTTTCT 30301 CAAGTTCAGA GTTTCGGAAA TGATGGCGGA TATCGTCAAA ATAGTTATCA CGATGGTGTG 30361 GATTTTGGAT CAATAGATCA TCCTGGTAGA GAAGTGCATT GTATTCATGG TGGAACGGTA 30421 ACTATCAAAT CAGCTATGGG TGGCTTAGGT AATTTTGTGG TTATTCATAC GCCGGAAGGA 30481 TTCAATATCG TTTATCAAGA AGCTTTTAGT TCTCCCTCTA ATATTATTGT TAGTGTTGGG 30541 CAAAAAGTAA AAACTGGTGA TGTAATTGGA TATCGTGATA CAGACCATGT TCATATTGGC 30601 GTAACTAAGC AAGATTTTTA TCAAGCAGTT CGAAATTCTT TTTCTCCTGC AGGTGGTTGG 30661 CTAGATCCAG TAAAACTAAT TAAAGAAGGT GGCGATGGGT CTAAACCACA AGAAGGAAAG 30721 AAAGATCAAA CTGTTGATAA TAGTAATGCT GCACGTCCTA AATTAACCAT TACTACTGTC 30781 AATAACGGTA GAGACTATAT TGATATTCCT GATTTACAAA AAGAATTCGG TATTATTGAG 30841 GGAACTGTTG AATTTGATAA TGTGATGAT CCGAATGTTT TAATGCAACA AGCTCAAACA 30901 TGGATAAGG CTCAAAGAAT ACCTCAAAGT TGGGAAGTA CAGCTTTAGA ATTACK 30961 ACAAACTTCA AATCTTTAA GGTTGCTGAT AGGTACATGT TTATTAATCC AAATGTTGCA 31021 AAACCCCAAT TACTACTAGE TACTCAAAAA GAAATTCAAT TACTAAAGCC CCATGCGTCT 31081 TCTACTTACT TTGGTGATAA ANSWERGGGG CTTACTGATT ATTACTGATT AAATCAAGTC 31141 AATTTCAAC AATTTAAGGA AATTCGAGTG ATGGTTAATC AGGTTGTCCA AACCCAAGAG 31201 CAATCTGCTA ATAACAATAA TAAGGTTATG CAAAATTTTG CTAGTAGTGC TGATCTTGCA 31261 CHANGE CHANGE TAG AAATCTTCAA CHANGE CHANGE ACG ATCGTGCTCG CHANGE CHANGE 31321 GTTTCCTTAG AAGAATTCAA TAAACTAAAG REVIEW AAAAACTAAC AACAGGAGGC 31381 GROUPATG GCAAGTGAAA CCTATGROUP TGAGTCATTT GROUPTAGGG ATCHATAT 31441 GAAACAAATC GCTGACCCTA TTCGTCACAA GGGTTATGGA AAAGATGTGC GTGAGGCAAT 31501 TGCACAGGGC TTCGAAAACT CENTRALAACA TTTAAGAGGT ATTGAAGAG AACTGAAACA 31561 ACAAGAAAAG AAAAAGTCAT CGTCTATGGA TGATATTTTT AATTCTTTTG GTAAGAAGGA 31621 GTGATGATAA ATGGCAAAAG AGATTAGTAA TCTGATTACC TTTAACACCT ACAAATTTGA 31681 ACGAGGCGGC CTTTTGGTTG ATATGTTTAA CCAATTTAAT GCTCGTGTAG GAGATCAAGG 31741 AACGGAATTA GCCATCCAGT GGGAAACTAG TAAGACTGAA ACTAAAATTA ATTTAAAAGA 31801 ACGAGGATTA CATTTCTTTG GGACAGGTTC AGTTGGACAG TACCTTGAAA AATTAGAAGA 31861 TGGAACTGGC TTTAAGATGT CTGCAGATGC ATCTACCGTT GAATGGGAAG ATAAAGATGA 31921 AGCTGGTAGT TTAGACGATG GAATTACGGT TGTTAAGTTG CCAAAACAAT TTTTCCCTCA 31981 AAAAGGTATT TTCTTTGGTT ACTTTGGCCT AAAAGATAGA CAAGGTAATA TCTTTACTAG 32041 TGTTAATGTT TGGTTCCGTG TTCTTGGCGG TGTTCCAACG ATGGGGGCTG CTATTCCTTA 32101 CTTTGTTACT GAATTTGATG AAGTATTAGA GCGATGCAAT GGTAAGATTA TTGACGCTTT 32161 AGCAGAATTA CGTGAAAAGT ACCAGGCAGA AGTTAAGAAG AATGAGGATA TGTCTGCGGA 32221 AACAAGAGCA GCGTTGAGTA AACTTGCTGA TGCTGTTGGT GCAATTCAAG CGCAGATTGA 32281 TGCAGGTAAT GTAATTACAC GTAAAGAATA TAATAATCTT GCTAATCAGA TTGATAATCG 32341 CCTTAGTAAA ATGACACAGA ACATTGAGAG TTTTTCATCA CTCGATGACT TAAAAGCTCA 32401 ATATCCTAAT GGAAAAGATG GACTCTTTGT TACTAATGAC AATAATCATA AGTATCAATA 32461 CAAGAATGGA TCATGGGTAG ATGAAGGTAT ATGGACAGTT ACTACCTTTG ATCCAGAAAC 32521 GCGACGACGC CTTACATACC TTGATACATC TAATTCTATT TTGCAAAAAT CACTCAGTGA 32581 ATTGACTAAA GAAGTCGTTG ATATAAATTG GTTTTTAGGC GAAATTGATG CAAATACTGG 32641 TAAAATTACA CCTCACGAAA GTTTTAATCG TGCATACTCA TCACTCAAAG TAATTGGTAA 32701 ATCACATGCT TTTGAATTTT TGCTTAATAC TGATTATTTG CAATATATTTA GTATTTTTGA 32761 ATTCAATTCA AATGGGGAGA TTATTAAGCA CGATAGTGTT GGCGATAAAG CGATATATAC 32821 ATTTGAAAAG GATACGACTG CGGTAAGGTT TCAGATTACT AGTACTGCTG CTACTATGAA 32881 GCAAAATGAT TTACGCGATA CTATTCAAAA TAGTGGGCTA AAAATTATCG ATCGAGGACA 32941 CCGTTCAGTA ATTAATGATA TTGATCATTT ATATATCCGT GAACATTTAA TGCCGATTGA 33001 AGCAATTGAA GGCTATACAA TTAACACTAA TGTTGATTAT GGTGAAACTG TTGATGTATC 33061 ACATCCAATA GTAACGTCTG CGTTTCAATA TATTAATCAA GTATGTAAGC CGGGCGATAT 33121 TTTCGTAATT AATAATCTAT CTGGAGGCTT TAACGCAATG GCTTGGGCCT TTATTGATAG 33181 CGAGAACCGG TTAATTCAAA AATCTGAAGT AAACTTATCT CAATCTCAGG TTACTTTATA 33241 TGCGCCAAGT AATGCTGCAA AATTAATTAT CAATAATATG GATAGTAACT GTACAGCATA 33301 TAGATATACT CCGGATAAAG AACATTTTAGC TAAAATTAAT ATTGCTTTAA CTACCAATAT 33361 TCATCGAAAT ATCAAGTTAG CTTATCAAAC AGGAGAAACA GTCTCATTAA TTCCTGAAAA 33421 AGTAAGTAAT TACAAATATA TTATATTAGA TTGTAATTTT AATGATGCTT TCAGAATAAA 33481 GGGTTATGGT GGATTGAATC CACGATTATA TGGATTTATT TCTGAGCAAA ACACATTAAT 33541 GAATGTTGCG CCTGCAAATG TTAATGATCA ATTAACTGAT GTCTTTATCA AAACGCCAAA 33601 AGGCGCCAAA AAATTAGTAG TTAATTCAA TCTTGATCAA SECTIONAATC CCAAACAAAT 33661 TGCTGAACTT TATAAGCTTC SECTION TGTTATTACT GAGCAAAAAA TAAAAAAAAA 33721 TTTATTGAAT SPIRIT TCGATACATT ATTTCTAGT TTATTGATG GTATTACT 33781 TGGTAAAGAT TTAGCCAATC ATCTTGCGGA TTTTGCTAAA AGCGGCGATA AAATGGTTCA 33841 TGTATCAACG TTTTATAAAG TTAACGATAC TCTTTTTATG TCTTATTATG CTAATACAAG 33901 ATCGGCTTAC GAAGATCCAA CCCAGCATAC AGCACGATTA GTTTATGCAC CGTTTGAGAA 33961 TCTAAATCAA CAAACGTACA TCGATGTAGC CGACATTGGA CAAATATA ATGGTCAAAA 34021 CROWDING ATTACK CTTTGCTTCT CROSSING CROWDING ATTACK 34081 TGCCTTTACT GCTAAGGTAG GTGGTAAGTT CTATATGCTT TACCGTCGTT TTGATCCTAA 34141 RESPONSIBILITY TTAGCTG TTCATACAAT RESPONSIBILITY GTTGCTAA TGACGTCGAC 34201 ATTTGATACA GTAAGCGTTC ATGATTTGTT AGCTAAGGCA GGAATTGACT ATGATTATGA 34261 AGATCGTGAT ATTTCCTTTG TCCAAAAATT AAGTCCACGG ATTGAAGATG GCGTAGTGCA 34321 ATACTATGCA GGTATCGGAA TCTTACATTT TTGCTTTGTA GTAAAATCAA GCGACTTAAT 34381 CAACTGGACT TTTGTCAGTA CTCCAGACTT TATGTACAAG CCAGAATTTG AACCTTCTGT 34441 ATATGTTAAG GGAGACAATG TTTATTATTT TTGTCGTCAG CGAGGGACAG AAGGTAATGC 34501 AGTTTTAGCT AAGTATAATA TCCCTAATGG TCAATGGTCG AATCCGATTC TTGTACCAGA 34561 TACTCAATCA CGCTATGACT TTTTCGAGAA TAATAGTCAG TTGTACCTTG TTCATTCACC 34621 GCTAGACCGT AATCATATTA GTTTGATGCA GATTGATCAG AATGTTCTGG AAAAGAGCTA 34681 TGAAGTAGCA ACAGCAGTAG TACAAGATTG CTTCTACCCA TTTACTCAAA ATATTGATGG 34741 TCAGATGTAT ATGAGCTTTA CACAAAGTAG GCAACATATT TGGCTAAATA AATTTAATCC 34801 CCACAGTCTG CTAGATAGTG ATGTAGCAAC TATTTTCAGT AATTTAATTG AGTAGCAAAA 34861 CATAGTCGCC TTATAAATAC ACAATACATA GAAAGTTGCA TTGCTTAAAT GGAAACTTAA 34921 TGGGCGGCTT ATAGACTTTT ATTATTTAAA AGAGTATACT GGAATTATTC TTTTTATTGG 34981 GAGGAAATAT AAAAGTGACA ACTAAAGTGA GAGATAAATC GCTTGATATT ATCCGGGGGA 35041 GCATCCTTCT AGTTGTCTTG GGTCATATAT CTGGGATACC TTTTGAGTTA AAAAAGTACA 35101 TATATTCTTT TCATATACCA CTGTTCTTTT TTGTTTCGGG ATATTTGTTC AACTTTGCTA 35161 AATACAGGTA TTTTTCTTAT AAAGAGTTTA TAAAATATAA AGCTAAAAAA TATATCCTAC 35221 CTTATTTCAG AATGGGGTTG ATATGTTTGC TTCTATTTGG CATAGTTTAT CCACTATTTG 35281 CTGAAGGGTT TAGTAAACAG TATATGCTTC AATCTACAAA ATATGTTTTA GGTTTACTAT 35341 ACTCGCGTGG AGGTCCTAAT TATATGGCCT GGAGTTCGCC ACTTTGGTTT CTAACAGCCT 35401 TATTTATTGC AGAGATTATT TTTTTTGTGG TTCTAAAATT TAATTTTAAA TATCCATTAA 35461 TAGTGTTTGG AATCTTAGCT ATATTGAGTT ATATTTACTC GATTACAATT AAAATTCGT 35521 TACCGTGGAA TATTGATGTT GCAATGTTTG CAGTGTTATT CATGTACCTA GGCTTTATTA 35581 CACACAAATA TAATTTAACT AAGCACATTA ACTTACCGGT TTTCTTACTT TTGATTGTTA 35641 TTTTTGTATT ATCTGTAGCT TACAATAATG AGATTGACAT GAATTTAAGA AACTATGGCA 35701 ATGGATTTTT AACAATTATT AGTGGAACAA TAGGTACTGT TATATGCTTG CAAATTGCGC 35761 GATTGTTAAA AGAGAATAAG ATATTAGAGT TTTATGGTAA AAACACATTA TTTATCATGG 35821 GCTACACGTA TGCTGTGTTT AATTGTATTT TGGCTTTAAG CAGCCATTTT AGTACTGTAA 35881 AGAATGTTGT AGCTTCGTTT TTGATTCAAA TTATAATTTTT AACTTTATTA ATAGTACTGA 35941 AGAATTTTT CAAACAAATA AAAAAGCCCA TTTATGCATA TACTAGGAAA ATTACK 36001 AAAAAAACTA ATACGTCCTA CTCAGGGCGT TTTTATTTTA CCTTCAAAGG AGATGATCAA 36061 CATTGCCCTA TCATTTATTT ATGCTGCACC AAATGCAGAC ATTACK THROW 36121 TGTGGGCTTT TACAATCGTG ATGATTGTAG ATTAATTAC GGGAATGATT AAACCGTATT 36181 ATGCAAAGAA AACAATTAAG AAAACTAATA GTTCAGTTGG AATCCCTGGG ATAATTAAAC 36241 ACACAGTAAT TTATTTAGTG GTAGTAATTG CTTATCCATA TCTTTATACG ATTGGAGCAA 36301 GCACGATGGC TACCACTTTT TTAATTGCTT GGATTTATCA ATTATT TCAATTGTAG 36361 AAAATTGGAC AGAGATGGGG TGGTGGTTGC CTAAACCAAT CATGGATTTC TTTGAAGCCA 36421 AATTAGCTAA GGATCAAGAA GATTATGACC CATCTAAGTA CAATTTTCTT GGTAAATATA 36481 AAGGAGGTAA AAAGTAA (SEQ ID NO: 13). [Example]

[0060] Selection of L. reuteri promoters and transcription terminators. Comprehensive proteomic analysis of L. reuteri 3632 pellets and culture supernatants will be performed to identify potential strong promoters and secretion signals, respectively. Proteins in the pellets and supernatants will be ranked by expression level, and promoters and secretion signals from highly expressed, secreted proteins will be identified by whole-genome sequencing (Example 2). Genetic elements will be selected for use in expression cassettes that can be used to create genetically modified bacteria that deliver desired biomolecules to host animals in need thereof. The expression cassette will include a suitable promoter, a heterologous coding sequence encoding the desired biomolecule, and a transcription terminator. The heterologous coding sequence could include a signal sequence for secretion, a cell wall anchor sequence, and / or a detectable peptide tag.

[0061] Six suitable promoters are identified by analysis of the comprehensive proteomics data, and their promoter sequences are as follows: Xylulose-5-phosphate phosphoketolase promoter

[0062] [ka]

[0063] (SEQ ID NO: 14); elongation factor TU promoter

[0064] [ka]

[0065] (SEQ ID NO: 15); glyceraldehyde-3-phosphate dehydrogenase promoter

[0066] [ka]

[0067] (SEQ ID NO: 16); glucose-6-phosphate dehydrogenase promoter

[0068] [ka]

[0069] (SEQ ID NO: 17); L-lactate dehydrogenase promoter

[0070] [ka]

[0071] (SEQ ID NO: 18); and the tuf promoter

[0072] [ka]

[0073] (SEQ ID NO: 19). The underlined region in the above sequence indicates the ribosome binding site.

[0074] Four suitable secretory signal peptides are also identified by analysis of the global proteomic data. The secretory signal sequences may be derived from the following proteins: C-protein alpha-antigen precursor 1 MVSKNNHQFY QQKHAERKQR WGIRKLSVGV ASVLLGTTFM LYGNHAVLAD TVTSPSDDVT 61 RSTTTQGGNK DKVTEGTTEG TTSTPQTSGD STDKQANGQN WQQVPTTDT EEATNHQDTP 121 QGQDTTQNTT NVDKKDTEVT PANDATTPTT QKITAKFTTA KFTTAKFTAA KFKVLAARPV 181 MKVAGTASLP ISNQDIKLDS QPMLTEIINK PTDNWVYNNL KWYQDTSTEK IKEILQNHTA 241 NDESGRYYFA GVANYNEHYH AIYLLARSNN LNDNSLYVTI LHTGLGKNIQ EAWAPGESK 301 KVEYSGTTT PIFTNYDGTS ASIDLDGIEK GDNIYGMWG FAYGHNTGIK GDPASMGNGF 361 VMTPIPTKMT TTIHYIDQAT GDEIAVPKSF EGVAYQKYTI TGEAPTIDGY TLKKSPETTG 421 YISPYKVGES YDFRLDKHW IKQTVIDAQG LVRVTAYYDG EVLNNTTRYL GNKLNWDRM 481 SFISHGKWYT YINQITSTND GIVYYYAKDG SEDKSEVRVH YIDVTGSKNS IFVPGDGEEV 541 ATDKISGKLG ENYNYDWLP TDYNLATNQA NTVNGTYTID HHDEYVYWK 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 LTADEKTIE 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 KTSAEKLDP 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 PGDKWEGKS DAAKNEPKVP GDKVKVDDPN KLTEDEKSEV VKAVEDANKD 2401 ENGKSTLPEG SKVTVGDNGD VTVTYPDGSK DTIPGDKWE GKGTEGQTDA DKNEPKVPGD 2461 KVKVDDPNKL TEDEKSEWK AVEDANKDEN GKSTLPEGSK VTVGDNGDVT VTYPDGSKDT 2521 IPGDKWEGK GTEGQTDADK NEPKVPGDKV KVDDPNKLTE DEKSEWKAV EDANKDENGK 2581 STLPEGSKVT VGDNGDVTVT YPDGSKDTIP GDKWEGRGT EGQTDADKNE PKVPGDKVKV 2641 DDPTKLTEDE KSDVEQAIKD ANKDENGKST LPEGSKVTVG DNDDVTVTYP DGSKDTIPGD 2701 KWEGKGTEG QTDADKNEPK VPGDKVKVDD PNKLMEDEKS DVEQAIKDAN KDENGKSTLP 2761 EGSKVTVSDN GDVTITYPDG SKDTIPGDQV IEGKSDADKN TPNVPGGDKV KVDDPTKLTD 2821 NEKNAVKDKV DEANSNLPDG TKVTVGDDGT TTITYPDGST NTISGHDLVT GKTDADKYPL 2881 NPGQAVNWD PNHLTQAEQD QVKEAIQTTN PTAPIATITV DTAGNVQVTF ADGSTTTLQA 2941 NLHKHVVTEAT TGSAIKPGVG TNGGQTKGAT STNQTATKQQ AQQHLPQTGD QPATWAMLSG 3001 LGVAFLGLLG LKKKRED (SEQ ID NO: 20); Arabinogalactan endo-1,4-beta-galactosidase precursor 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 WNKFYHNWG 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 NLLSGKVLW YSTDFTNDDP QKITNTFMNS YDFTNADNSV 601 LGVGADLNKN KLVIILFKPG EKAEQPQATS TISASISDIF KKAGVNVVDVD NGLTKGSWN 661 SADLGNALTN GTAELLKGDK GTIISQEVLK AIFAAFAGNT SAVEGTKNYY NGNDAYHYEF 721 WLEGQSADDK LNNFLALNKG AKYGDQLKW YTATLVFGQE TGTNSNESKV PASERTDEQL 781 DLAYKTGTDT GLRYDSVKVE KIPGMTDDMV RGVDVSSYQA LINAGVKFYD FNGQESNLFK 841 ILKDSGWWV RLRVWNDPYN AQGQPYAGGD NNEENLIKMA KEASDNGLKL LIDFQYSDFW 901 TDPAQQILPK AWRNLSHGEM SQEVYLYTSK ILNDLQKAGA SVKMVQIGNE ITNGAFGLYT 961 GRRNGGGNWAS LWETSDGDQV AKYIQAGSSA VRRIDPTIKV AIQLETPEIN KYRGIMNVLK 1021 KNNVDYDYLG TSYYPFWSTT QGNGWYDNVD LGYGANTPW 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 NNKWTFVSA 1321 NKDAKYGQPL IA YSATVW DSEPGTQVAT SPLQIKISQV WNTWNEEIK IDNPLKQGDL 1381 ITDKSDNAFS GILNSKDIKE ALTGEKGKDV SESTWDVKS LLPKEVKGSK TYTTADGNQY 1441 YYDFWLASVE TSNWYGEPI IWYTASLKW LG (SEQ ID NO: 21); Chromosome segregation protein 1 MEKTMKKKAL VATTAVAGIT LVGEVTTVHA ADNVQQPWE QNWQSSQEE KQAAQNLQNA 61 QSDWTATEA NSNAQDNLAS ANNNLSNAKK AVSDQAAKVA DATKAQSDAS TKVDNDNKW 121 ADAQQKADQA TPA IENAKQ AIEGQNKVID QDNENIKYSN TDQDKAQNTL NNAQSNEDKA 181 NATLSNKKSS QASAQNNVKQ AEDALNGTHL VEAQNAFNQA QSNVENAQSK YDQANNQLSD 241 AQKKVTTNQN DLTAKNKALD NINNQVDTDQ NNWSNQATA 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 LLGLHWRKE DHQYFGLSTN MCPGSYMGQL 541 HFIIVENDPA YIKDPQTFNA KGGTTKIEYI DPKVQLNQQK DILTTTLSTQ QADLATKQDA 601 LNKA QNLAN 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 WKVTPITME AGTSLPDPVI ENGFTWTGT NQLFVSLAAI DSSNNNIPQG TKASWANRSK 901 ALTDSQNAGS YSEDILITFP DNSTVTVPVD LTVTAKKITE DQKATEGGYH IVNGSWDKQ 961 NNLVSGWTVK NGQMVDPEGN VIKTTMSTAQ GVTIEKNNSK SGNTKTNMIQ TSLTIANNKA 1021 TTNKDNQLPQ TGNYNNNTKV LGLAGIALAS ALTMFGYKKR QHN (SEQ ID NO: 22); D-gamma-glutamyl-meso-diaminopimelic acid endopeptidase Cwls precursor 1 MKSTTKKILA SSLGVAGAMA MGTVTAKADT TVTWAGDSL NGIAQKYNVS ADDIATANHL 61 QNKELIFVGQ KLTIPTKDKN ETPANNAEKK DQASKNSQSL QDSWKAMSY LGTPYVWGGN 121 KPGGFDCSGL VQYCYGIPQR TTYEQQALGP HIHDNVLNAP YGALVFYGSD DAPYHVAISL 181 GDGRIIQAPN ENETVKITDQ QYFPGNYYW MH (Chromosome Partition Protein) (Chromosome Partition Protein) Smc 1 MNKAQKVAD DTTAWNKQT DWNAAEAKK NADEALKNAN DAQTSAQKNK DAKQAIADEA 61 SVALADANTA VKDAQAKVDA INDKLANFNT ITLPAGYKDD LIAYYNYFGN SNYNQDEANN 121 LAQDLLKYRD QAMSQNKFKD NLSDDRWDI 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 DVKDKTAQ EANDNLTTAQ NDLATLQNQL SADQANQKQQA 421 QTTFDSFDAD LATKQANLQK ATDSLKAEQG RLAIAQADLD NANKALSDAN NNLAQKKW 481 ENDNETLKVD NDKLVQLQNN LSDLQNAPKL LAAAKEQVAT AQKALADAQE AYNVA DKLT 541 SLKQTAAGTT TNVSKAQQAL AEAKNNEDAA KEVLDQAQQA LTELRQKEAL AKQVAEEQAK 601 LAAEKEAKDN GYHIENNQW DAKGNSWGW TVKGNQIVSP TNATVDPAVS VTTNWVDSK 661 GQVQPQTSVT ANSVKTVAAT ESAPVATTT VQTREQYKQQ LKSNNQLPQT GNNDSAVLSL 721 AGVALAAMLS LFGIKKREY (SEQ ID NO: 40). One of skill in the art will recognize that due to redundancy in the genetic code, multiple nucleic acid sequences will encode the above peptide. [Example]

[0075] Expression cassette. Based on the information presented in the previous examples, expression cassettes can be designed to produce high levels of secreted target biomolecules. For example, one of these expression cassettes (CwlS_C2; SEQ ID NO: 23) evolved to deliver an endopeptidase (cell wall hydrolase) to the cell wall. This endopeptidase plays an important role in cell division and separation. Replacing the endopeptidase with a heterologous coding region would result in the secretion of a desired target biomolecule, such as an anti-infective biomolecule targeting pathogenic bacteria. A specific example is the high-level expression of the novel mersacidin disclosed herein by replacing the native mersacidin promoter with a strong promoter (Example 4; SEQ ID NOs: 14-19) and, optionally, a strong secretion signal (Example 4; SEQ ID NOs: 20-23).

[0076] Expression vectors are designed and synthesized with various combinations of some or all of the following components: an origin of replication for replication in L. reuteri (e.g., from a high copy number plasmid; SEQ ID NO: 8), an origin of replication for replication in E. coli, a drug resistance marker for selection, a strong promoter for expression in Lactobacillus, a signal sequence for secretion, a heterologous coding region encoding the desired biomolecule, an expression peptide tag for detection, a cell wall anchor for secretion, and a terminator for transcription termination.

[0077] Alternatively, a heterologous coding region encoding a desired biomolecule may be integrated into the chromosome of a genetically modified microorganism. Chromosomal integration of an expression cassette (containing a strong promoter for expression in Lactobacillus, a signal sequence for secretion, a heterologous coding region encoding the desired biomolecule, a terminator for transcription termination, and optionally an expression peptide tag for detection and a cell wall anchor for secretion) is achieved using a suicide vector. The suicide vector contains an origin of replication for replication in E. coli, a drug resistance marker for selection, and an expression cassette flanked by nucleic acids homologous to a specific region of the chromosome. An example of such a suicide vector is shown in Figure 3A.

[0078] For chromosomal integration, L. reuteri genes may be disrupted by the insertion of an expression cassette. A map of these chromosomal loci is shown in Figure 3B. Two genes that may be disrupted are transposase and uracil phosphoribosyl (UPP) transferase. Chromosomal integration may also occur within the pyrE locus, where pyrE excision and subsequent reinsertion may serve as a selectable marker for integration (Sakaguchi et al., Bioscience of Microbiota, Food and Health, 32:59-68 (2013)). Because recombinant bacteria cannot survive in environments without metabolic supplements, the modified pyrE gene may also be used for biocontainment of recombinant bacteria. [Example]

[0079] Enzyme genes for inclusion in expression cassettes. The expression cassette will contain a heterologous coding region encoding a desired biomolecule. The desired biomolecule may have anti-infective activity, such as specificity for a particular genera of pathogenic bacteria, e.g., lysis of pathogenic bacteria by lytic enzymes derived from bacteriophages.

[0080] The lytic enzyme is PlyCM, a lytic enzyme that targets Clostridium perfringens and is encoded by the following sequence: 1 ATGGAAAGCC GTAATAACAA TAACCTGAAG GGCATCGATG TGAGCAACTG GAAGGGCAAC 61 ATCAATTTTC AAAGCGTCAA AAATGACGT GTTGAAGTTG TTTACATTAA GGCAACCGAA 121 GGCAACTACT TCAAAGACAA ATATGCTAAG CAAAACTACG AGCGCGCTAA AGAACAGGGT 181 CTGCGTGTGG GCTTCTACCA CTTTTTCCGC GCAAACAAAG GTGCCAAAGA TCAGGCGAAC 241 TTCTTCGTGA ATTACCTGAA CGAAATCGGT GCGGTCAATT ATGACTGTAA ACTGGCACTG 301 GACATCGAGA CTACCGAAGG CGTCGGTGCG CGTGACCTGA CCTCTATGTG CATCGAGTTC 361 CTGGAAGAGG TGAAGCGTAT TACGGGTAAG GAAGTTGTCG TGTACACCTA TACCAGCTTC 421 GCGAACAATA ATCTGGATTC CCGTCTGTCT AGCTATCCGG TGTGGATTGC GCACTATGGC 481 GTCAACACCC CGGGTGCGAA CAATATCTGG AGCGAGTGGG TGGGTTTCCA GTACAGCGAG 541 AATGGCTCCG TCGCCGGTGT CAGCGGTGGC TGCGATATGA ACGAATTTAC CAATGGTATC 601 TTTATTGACT CGAACAATTT CACGTTGGAC AATGCAACGA CCAAAAATGT TAGCATTAAG 661 CTGAACATTC GCGCCAAGGG TACGACCAAC AGCAAAGTTA TTGGTAGCAT TCCGGCGAAC 721 GAAAAGTTTA AGATCAAATG GGTTGATGAA GATTACCTGG GTTGGTATTA CGTTGAGTAT 781 AACGGTATCG TGGGTTACGT TAACGCCGAT TACGTCGAGA AACTGCAAAT GGCGACCACG 841 CATAATGTTA GCACCTTTCT GAATGTACGC GAGGAGGGTT CCTTGAATAG CCGTATTGTG 901 GACAAGATCA ACACTGGCGA CATCTTTCGT ATTGACTGGG TTGATAGCGA TTTCATTGGT 961 TGGTATCGTG TGACGACGAA AAACGGCAAG GTCGGCTTTG TTAATGCAGA GTTTGTGAAA 1021 AAGTTGTAA (SEQ ID NO: 24); PlySS2, a lytic enzyme targeting Streptococcus suis and Staphylococcus aureus, encoded by the following sequence: 1 ATGACAACAG TAAATGAAGC ATTAAATAAT GTAAGAGCTC AGGTTGGGTC CGGTGCGTCT 61 GTTGGCAACG GCGAATGCTA CGCTTTGGCT AGTTGGTACG AGCGCATGAT TAGTCCGGAT 121 GCAACTGTCG GACTTGGCGC TGGTGTGGGC TGGGTCAGCG GTGCAATCGG CGATACAATC 181 TCTGCCAAAA ACATCGGCTC ATCATACAAC TGGCAAGCTA ACGGCTGGAC AGTTTCCACA 241 TCTGGTCCAT TTAAAGCAGG TCAGATTGTG ACGCTTGGGG CAACACCAGG AAACCCTTAC 301 GGACATGTGG TAATCGTCGA AGCAGTGGAC GGCGATAGAT TGACTATTTT GGAGCAAAAC 361 TACGGCGGGA AACGTTATCC CGTCCGTAAT TATTACAGCG CTGCAAGCTA TCGTCAACAG 421 GTCGTGCATT ACATCACACC GCCTGGCACG GTCGCACAGT CAGCACCCAA CCTTGCAGGC 481 TCTCGTTCCT ATCGCGAGAC GGGCACTATG ACTGTCACGG TCGATGCTCT CAATGTTCGC 541 AGGGCGCCAA ATACTTCAGG CGAGATTGTA GCAGTATACA AGCGTGGTGA ATCATTTGAC 601 TATGATACTG TCATCATCGA TGTCAATGGC TATGTCTGGG TGTCTTACAT AGGCGGCAGC 661 GGCAAACGTA ACTACGTTGC GACGGGCGCT ACCAAAGACG GTAAGCGTTT CGGCAATGCT 721 TGGGGTACAT TTAAATAA (SEQ ID NO: 25); and CP025C, a lytic enzyme that targets Clostridium perfringens, encoded by the following sequence: 1 ATGTCGAAGA TTTTTGGTTT AGATGCGGGT CATTGTACGA GCGGCGCAGA TACGGGTGCG 61 CAGGGCAATG GTTACAAAGA ACAAGACTTG ACCCGTCAAG TTGTTACCTA TCTGAGCGAA 121 TACTTGGAGA AAGAGGGCCA CACTACCAAG TACTGCCATT GCAATAGCGC GAGCACGGTT 181 AACGAATCCC TGCGCTATCG TGTGAACAAA GCCAACTCCA TCGGTGTCGA CTACTTCGTG 241 AGCATCCACC TGAACGCCGG TGGCGGCGTT GGTACCGAAA CGTACATCTG CGCGCGTGGC 301 GGCGAGGCCG AGCGCGTGGC GAAACGCGTC AATTCTAAAC TGGTGCAGTA CGGTTATCGT 361 GACCGTGGTG TCAAGGTTGG TAATCTGTAT GTGATTAAGA ACACCAATGC ACCGGCTATC 421 CTGGTTGAGA TCTGTTTCAT TGACAGCAGC AGCGATGTGG CAAAGTTTAA CGCGAAGGCA 481 ATCGCGAAAG CGATTGCTGA GGGTCTGCTG GATAAAACCA TTGGTGAAGT CGAGAATAAG 541 TAA (SEQ ID NO: 26) Examples include:

[0081] Furthermore, two of the three vegetative prophage sequences found in L. reuteri strain 3632 contain putative lytic enzymes. These lytic enzymes may be used to target pathogenic bacteria or to control the environmental spread of genetically modified lactobacilli. These two lytic enzymes are: N-acetylmuramoyl-L-alanine amidase sle 1 precursor from prophage locus 1, which has the following nucleic acid sequence: 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 CTCTTGGTTA CAAGAATCT 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 CACCACAAC CCGGTTCAAC ATATTGGTCA CCCAGGCTACT 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 (SEQ ID NO: 27), and peptidase family M23 from prophage locus 6 having the following nucleic acid sequence: 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 (SEQ ID NO: 28).

Example

[0082] Single chain antibodies and their activities. The expression cassette will contain a heterologous coding region encoding a desired biomolecule. The desired biomolecule may be a biomolecule with anti-infective activity. The anti-infective activity may be the inhibition or neutralization of toxins produced by pathogens. Inhibition or neutralization may be achieved by single-chain antibodies. Lactobacillus has been demonstrated as an expression system for single-chain antibodies directed against host adhesins (WO2012 / 019054). Toxins targeted by single-chain antibodies include C. perfringens alpha toxin and NetB.

[0083] Camelid heavy chain-only (VHH) antibodies against C. perfringens alpha toxin and NetB are produced by QVQ Holding BV (Utrecht, NL). Briefly, two llama pups are each immunized with either recombinant alpha toxin or NetB variant W262A. Neither of these immunogens is hemolytic. Immunized llamas are boosted twice with toxin peptides. Blood samples are collected and RNA is isolated 44 and 72 days after the primary immunization for phage library construction. The phage library is screened for binding activity to each of the two toxins. Candidate antibodies are sequenced and further screened in bioassays as described below.

[0084] Alpha toxin causes membrane damage in a variety of red blood cells and cultured cells. It is preferentially active against phosphatidylcholine (PC or lecithin) and sphingomyelin (SM), two major components of the outer leaflet of eukaryotic cell membranes. The N-terminal domain has full activity against phosphatidylcholine but lacks sphingomyelinase activity and is not hemolytic or cytotoxic. The C-terminal domain has no enzymatic activity, but the interaction between the N- and C-terminal domains is essential to confer sphingomyelinase activity, hemolytic activity, and cytotoxicity to the toxin. Although alpha toxin is a potent hemolysin, lysis of red blood cells is only seen after intravenous administration of the toxin to experimental animals or in cases of clostridial sepsis.

[0085] The inhibitory ability of VHH antibodies directed against alpha toxin on alpha toxin lecithinase activity is determined by measuring its effect on egg yolk lipoproteins. Fresh egg yolks are centrifuged (10,000 x g, 4°C for 20 minutes) and diluted 1:10 in PBS. Two-fold dilution series of VHH (two wells per dilution, starting concentration of 5 µM) are added to a constant amount of alpha toxin (5 µg / ml recombinant alpha toxin or 3.33 x 10 -4 The ability of VHHs to neutralize alpha toxin activity is assessed by preincubation with either 100 μg / μl alpha toxin (Sigma, P7633) for 30 min at 37°C followed by the addition of 10% egg yolk emulsion. Serum from pups immunized with recombinant alpha toxin is used as a positive control, starting at a 1:4 dilution. After 1 h of incubation at 37°C, the antibody was measured at 650 nm (A 650 ) was measured. Alpha toxin activity is indicated by the development of turbidity, which results in an increase in absorbance.

[0086] The control serum was able to neutralize the lecithinase activity of both commercial and recombinant alpha-toxin. While an 8-fold dilution of the antiserum (corresponding to 3.12% serum) was able to completely neutralize the lecithinase activity of recombinant alpha-toxin, only the highest dilution of the antiserum (corresponding to 25% serum) was able to completely neutralize the lecithinase activity of commercial alpha-toxin. Significant differences in inhibitory potency were observed among the five candidate VHH antibodies. VHH EAT-1F3 had no effect on the lecithinase activity of either alpha-toxin. The neutralizing potency of EAT-1A2 and EAT-1C8 was very similar and was the same for both recombinant and commercial alpha-toxin. The maximum inhibitory potency was maintained up to a 32-fold dilution of VHH (0.16 μM VHH). However, neither EAT-1A2 nor EAT-1C8 was able to completely neutralize the lecithinase activity, resulting in 40% to 50% remaining lecithinase activity. Two other VHHs, EAT-1F2 and EAT-1G4, show differences in neutralizing potency against recombinant alpha-toxin and commercially available alpha-toxin. EAT-1F2 has high neutralizing potency against recombinant alpha-toxin but cannot completely neutralize commercially available alpha-toxin, resulting in approximately 25% remaining lecithinase activity. In contrast to EAT-1F2, EAT-1G4 neutralizes 100% of the lecithinase activity of commercially available alpha-toxin but has low potency in neutralizing recombinant alpha-toxin.

[0087] Neutralization of alpha-toxin hemolytic activity by VHH antibodies directed against alpha-toxin is determined by measuring its effect on sheep erythrocytes. Similar to the inhibition of alpha-toxin lecithinase activity, a two-fold dilution series of VHH antibodies (two wells per dilution, starting concentration of 5 μM) was added to a fixed amount of alpha-toxin (6.25 × 10 -5The ability to neutralize hemolytic activity is assessed by preincubating with 100 μl / μL alpha toxin (Sigma, P7633) for 30 minutes at 37°C followed by the addition of 1% sheep red blood cells. Serum from a pup immunized with recombinant alpha toxin is used as a positive control, starting at a 1:4 dilution. After 1 hour of incubation at 37°C, the plate is centrifuged to pellet intact red blood cells. The supernatant is transferred to a new 96-well plate and analyzed by A. 550 Alpha toxin activity is indicated by an increase in absorbance due to the release of hemoglobin from red blood cells.

[0088] Because recombinant alpha toxin did not exhibit hemolytic activity, only commercially available alpha toxin was used to determine the inhibitory ability of VHH antibodies against alpha toxin hemolytic activity. Up to a 16-fold dilution of the control serum (corresponding to 1.56% serum) completely inhibited alpha toxin hemolysis. In contrast, none of the candidate VHHs had any effect on alpha toxin hemolytic activity. Because the control serum contained polyclonal antibodies but the VHHs were monoclonal, the combined effect of all five VHHs (corresponding to 1 μM of each VHH at the highest dilution, 5 μM VHH overall) against alpha toxin was determined. The combination of VHHs had no effect on alpha toxin hemolysis.

[0089] Based on the above results, EAT-1F2 and EAT-1G4 were selected for further characterization. The peptide sequence of EAT-1F2 is: EVQLVESGGGLVQAGGSLRLSCAGSGRTGSLYSMGWFRQAPGKEREFVAAITWRPSSTYYADSVKGRFTISRDDAKNTVYLQMNSLKPEDTAVYFCAARPRGGLSPTPQAYDYWGQGTQVTVSSAAASGSLEQKLISEEDLNGAAHHHHHHGAA (SEQ ID NO: 29), and the peptide sequence of EAT-1G4 is: EVQLVESGGGLVQPGGSLRLSCAASGSIATINDMGWFRQAPGKQRDWVATIVSDGSTAYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCSARRHYGQGTQVTVSSAAASGSLEQKLISEEDLNGAAHHHHHHGAA (SEQ ID NO: 30) is.

[0090] The R27H mutant of EAT-1F2 (SEQ ID NO: 49) may be generated to improve the protease resistance of the antibody.

[0091] Those skilled in the art will recognize that due to redundancy in the genetic code, multiple nucleic acid sequences will encode the above peptides, although an exemplary sequence encoding EAT-1F2 is: 1 GAGGTGCAGC TCGTGGAAAG TGGCGGAGGT CTTGTTCAGG CTGGGGGATC GCTCCGTCTG 61 AGCTGTGCGG GGTCTGGCAG AACAGGTAGT CTCTATTCCA TGGGTTGGTT TCGGCAGGCC 121 CCGGGTAAGG AGCGGGAGTT CGTTGCAGCG ATTACGTGGA GGCCCAGCTC TACCTACTAC 181 GCGGACAGCG TAAAGGGACG ATTCACCATT AGTAGAGACG ACGCAAAGAA TACTGTATAT 241 TTGCAGATGA ATTCGTTGAA GCCTGAGGAC ACCGCTGTCT ATTTTTGCGC GGCGCGACCG 301 AGGGGCGGTC TCTCCCCGAC ACCTCAAGCA TATGATTACT GGGGACAAGG GACCCAAGTC 361 ACTGTATCCA GTGCGGCCGC GAGCGGCAGC CTTGAACAAA AGCTGATAAG CGAGGAGGAT 421 CTCAATGGTG CTGCACATCA TCATCACCAT CACGGGGCAG CG (SEQ ID NO: 31), and an exemplary sequence encoding EAT-1G4 is: 1 GAAGTTCAGC TTGTAGAGTC CGGTGGGGGT CTTGTACAGC CCGGCGGGAG CTTGCGACTC 61 TCATGCGCTG CTTCCGGAAG CATTGCGACA ATAAATGATA TGGGTTGGTT TAGACAAGCC 121 CCCGGGAAGC AGCGTGACTG GGTCGCGACT ATTGTGAGTG ACGGCAGCAC GGCTTATGCG 181 GACTCAGTGA AAGGGAGATT TACGATTTCG CGAGATAACG CGAAAAACAC TGTATACCTG 241 CAGATGAATT CACTCAAGCC GGAAGATACA GCTGTGTATT ATTGTTCTGC CCGACGGCAC 301 TACGGACAGG GGACCCAGGT CACAGTCTCG AGCGCTGCCG CCAGTGGGTC ACTCGAGCAG 361 AAGCTGATAT CAGAGGAGGA CCTTAACGGT GCGGCGCACC ATCACCACCA TCATGGTGCG 421 GCG (SEQ ID NO: 32) It would be.

[0092] NetB is a heptameric beta-pore-forming toxin that forms a single channel in planar phospholipid bilayers. NetB activity is affected by membrane fluidity and cholesterol, which enhance NetB oligomerization and play an important role in pore formation. NetB has high hemolytic activity against avian erythrocytes.

[0093] Neutralization of NetB hemolytic activity by camelid VHH antibodies directed against NetB is determined by measuring NetB-mediated lysis of chicken erythrocytes. A two-fold dilution series of VHH antibodies (two wells per dilution, starting at 5 μM) is preincubated with a fixed amount of NetB toxin (20 μg of recombinant NetB) for 30 min at 37°C, followed by the addition of 1% chicken erythrocytes, to assess their ability to neutralize NetB hemolytic activity. The atoxic NetB variant W262A is included as a negative control, as this variant does not exhibit hemolytic activity. A positive control serum from a rabbit immunized with recombinant NetB (wild-type NetB) is used, starting at a 1:4 dilution. After 1 h of incubation at 37°C, the plate is centrifuged to pellet intact erythrocytes. The supernatant is transferred to a new 96-well plate and analyzed by A. 550 NetB activity is indicated by an increase in absorbance due to the release of hemoglobin from red blood cells.

[0094] The control sera are able to neutralize the hemolytic activity of NetB. The VHH antibodies ENB-1F4 and ENB-IFIO have no effect on NetB hemolysis. ENB-1B9 has a moderate inhibitory capacity, whereas ENB-1D11 and ENB-1A4 have an inhibitory capacity at 4- to 8-fold dilutions. (VHH of 1.25 μM to 0.625 μM) can neutralize NetB hemolysis.

[0095] Based on the above results, ENB-1A4 and ENB-1D11 were selected for further characterization. The peptide sequence of ENB-1A4 is: EVQLVESGGGLVQAGGSLRLSCAASGSIFSTNVMGWYRQAPGKQREFVAGITIGGTARYPDSVKGRFTISRDNTQNTVYLQMNNLKPEDTAVYYCNAVLPSDQRRWSWGQGTQVTVSSAAASGSLEQKLISEEDLNGAAHHHHHHGAA (SEQ ID NO: 33), and the peptide sequence of ENB-1D11 is: EVQLVESGGGLVQTGGSLRLSCTASGTIDMTYGLIWYRQAPGKERELVASIRRDGRTNYADSVKGRFTISIDNAKNSIHLQMNSLKPDDTARYYCNSPYHALWGQGTQVTVSSAAASGSLEQKLISEEDLNGAAHHHHHHGAA (SEQ ID NO: 34) is.

[0096] The R56H mutant of ENB-1D11 (SEQ ID NO: 50) may be generated to improve the protease resistance of the antibody.

[0097] Those skilled in the art will recognize that due to redundancy in the genetic code, multiple nucleic acid sequences will encode the above peptides, although an exemplary sequence encoding ENB-1A4 is: 1 GAGGTACAAC TGGTTGAGAG TGGGGGTGGT TTGGTGCAAG CCGGAGGTTC CTTACGTTTG 61 TCTTGCGCGG CTAGTGGGAG CATCTTTTCA ACAAACGTAA TGGGGTGGTA CCGCCAAGCC 121 CCAGGTAAGC AGCGGGAATT TGTGGCCGGG ATAACGATCG GAGGAACTGC GAGGTATCCT 181 GATAGTGTGA AAGGGCGTTT CACAATTAGT CGAGATAATA CACAGAATAC TGTCTATCTC 241 CAAATGAATA ATCTCAAGCC CGAAGACACA GCAGTTTATT ATTGTAATGC CGTTCTCCCC 301 TCTGATCAGC GTCGATGGAG CTGGGGACAA GGCACCCAGG TTACGGTTAG CAGCGCGGCA 361 GCGTCTGGTT CGCTCGAGCA AAAGCTCATA TCTGAGGAGG ACCTGAACGG GGCAGCCCAC 421 CATCACCACC ATCACGGAGC AGCT (SEQ ID NO: 35), and an exemplary sequence encoding ENB-1G4 is: 1 GAGGTACAGC TGGTGGAGTC CGGCGGTGGT TTGGTGCAAA CCGGGGGTAG TCTGCGGCTT 61 AGTTGCACGG CGTCTGGGAC AATAGACATG ACTTATGGTC TCATATGGTA CAGGCAAGCG 121 CCTGGGAAAG AGAGGGAACT CGTTGCGAGT ATCAGAAGGG ACGGCCGCAC AAATTACGCT 181 GATTCAGTGA AAGGGCGCTT CACTATCTCG ATCGATAATG CGAAAAACAG TATTCACCTT 241 CAAATGAACT CCCTTAAGCC CGATGATACC GCCAGGTATT ATTGCAACAG CCCATATCAC 301 GCACTTTGGG GTCAGGGTAC GCAGGTAACA GTGTCTAGTG CGGCAGCCTC TGGTAGTTTG 361 GAGCAAAAGT TGATAAGTGA GGAGGACTTA AATGGGGCGG CACATCACCA CCACCATCAT 421 GGGGCGGCT (SEQ ID NO: 36) It would be. [Example]

[0098] Multifactorial expression cassette. Expression cassettes may be designed and synthesized using various combinations of the following components: a promoter for expression, a signal sequence for secretion, a cell wall anchor for secretion, at least one heterologous coding region encoding a desired biomolecule, and a terminator for transcription termination. An expression cassette may contain multiple heterologous coding regions.

[0099] One representative expression cassette for expression of camelid antibodies is: 1 AAATTAAAAG GCTGGATTTT TTCGGCCTTT TTTTAGTGCA AATAATTATT TTTTACGTAT 61 TTATATTATA GGGCTAATCA CTAAACTAAT AATTAGTGGT TGAAGCGCTG AAAATTTTCT 121 GCTATTTTAT TAATAGTTTG ATAATAAAAT AATGATATTT AATATAAAGA GGGATAAACG 181 AAATAATGAA ATCAACAACA AAGAAAATTC TTGCATCGTC GTTAGGGGTA GCTGGCGCAA 241 TGGCAATGGG CACGGTAACT GCAAAGGCTG ATACGACCGT TACGGTCAAT GCTGGCGATA 301 GTTTGAATGG GATTGCTCAA AAGTATAATG TTAGTGCGGA TGATATTGCA ACCGCTAATC 361 ACTTGCAAAA TAAAGAGTTG ATTTTTGTGG GACAAAAGTT GACAATTCCA ACCAAAGATA 421 AAAATGAAAC AGAAGTTCAA TTAGTTGAAA GTGGTGGTGG TTTAGTTCAA CCAGGTGGTA 481 GTTTACGTTT ATCATGTGCT GCAAGTGGTT CAATTGCAAC TATTAATGAT ATGGGTTGGT 541 TTCGTCAAGC ACCAGGAAAG CAACGTGATT GGGTTGCTAC TATTGTTAGT GATGGTTCAA 601 CTGCTTATGC TGATAGTGTT AAAGGTCGTT TTACTATTTC ACGTGATAAT GCTAAGAATA 661 CTGTTTACCT TCAAATGAAT AGTCTTAAGC CAGAAGATAC TGCAGTTTAC TATTGTTCAG 721 CTCGTCGTCA TTATGGTCAA GGTACTCAAG TTACTGTTAG TTCAGCTGCA GCTAGTGGTT 781 CATTAGAACA AAAATTAATT TCAGAAGAAG ATTTAAATGG TGCAGCTCAT CATCATCATC 841 ATCATGGTGC AGCTTACTTC CCTGGAAATT ACTATGTTGT GATGCATTAA TATTCCCTTT 901 CACCTCACCT TTAATAATTT AAATTAGTAA TTATCTTGCG CATCACAAAA GAGTGCTATA 961 TACTATTTCA GATTAGAAAG TTTTATGAGG GAGACAAATT G (SEQ ID NO: 37), in which nucleotides 1 to 185 represent the promoter sequence from Cwls endopeptidase (SEQ ID NO: 41), nucleotides 186 to 262 encode the Cwls endopeptidase secretion signal (SEQ ID NO: 23), nucleotides 263 to 407 encode the LysM domain for attachment to exopolysaccharides, nucleotides 408 to 431 are a spacer sequence, nucleotides 432 to 854 encode the VHH EAT-1G4 (SEQ ID NO: 30), and nucleotides 855 to 890 are another spacer sequence ending in a stop codon for translation termination.

[0100] A second exemplary expression cassette for expression of a camelid antibody is: 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 TTAATTATT TTAAATTTA GGGAGGAAAAC CTATCATGGA AAAGACTATG AAAAAGAAAAG 301 CTTTAGTTGC AACTACTGCT GTAGCCGGTA TTACTTTAGT AGGAGAGGTT ACTACTGTTC 361 ATGCCGCTGA CAATGTACAA CACAGTTC AATTAGTTGA AAGTGGTGGT GGTTTAGTTC 421 AACCAGGTGG TAGTTTACGT TTATCATGTG CTGCAAGTGG TTCAATTGCA ACTATTAATG 481 ATATGGGTTG GTTTCGTCAA GCACCAGGAA AGCAACGTGA TTGGGTTGCT ACTATTGTTA 541 GTGATGGTTC AACTGCTTAT GCTGATAGTG TTAAAGGTCG TTTTACTATT TCACGTGATA 601 ATGCTAAGAA TACTGTTTAC CTTCAAATGA ATAGTCTTAA GCCAGAAGAT ACTGCAGTTT 661 ACTATTGTTC AGCTCGTCGT CATTATGGTC AAGGTACTCA AGTTACTGTT AGTTCAGCTG 721 CAGCTAGTGG TTCTAGTGG COUNTY TTCTAGTGTC NATIONAL GGTGCAGCTC 781 ATCATCATCA TCATCATGGT GCAGCTAAGA NATIONAL AGATCAAAAA GCAACAGAAG 841 GCGGTTATCA TATTGTTAAT GGATCTGTTG TAGATAAGCA GAATAACTTG GTTAGTGGTT 901 GGACTGTTAA GAATGGTCAA ATGGTTGATC CTGAAGGTAA CGTTATCAAA ACAACAATGT 961 CTACAGCCCA AGGTGTTACT ATTGAAAAAA ATAATAGCAA GTCCGGGAAT ACAAAGACAA 1021 ACATGATTCA AACTTCTTTA ACTATTGCTA ACAACAAGGC AACAACAAAC AAAGACAACC 1081 AGTTACCACA AACTGGCAAT TACAACAACA ATACAAAGGT ATTAGGATTA GCTGGTATTG 1141 CACTTGCATC TGCTTTAACT ATGTTTGGAT ACAAGAAGCG CCAACATAAC TAATTTTCTT 1201 ACTTGATGGG TTTCTAAATA AAAAATGGAC TACTTCAGCT CAAGGTAGCC CATTTTTATT 1261 ATTATAGTGA AGCAGTTATT CTTACGTATA ACCAGACTAA AATATAATAA AATCTATTA 1321 TATATTAATC AACATCTCGG TTTAATCGTT AAAACTCCTC TGAGAGCTAA TTGTTAATAT 1381 TGAGTTGTAT AGT (SEQ ID NO: 38), in which nucleotides 1 to 275 represent the promoter sequence from the chromosome segregation protein (SEQ ID NO: 42), nucleotides 276 to 383 encode the secretion signal from the chromosome segregation protein (SEQ ID NO: 22), nucleotides 384 to 806 encode the VHH EAT-1G4 (SEQ ID NO: 30), nucleotides 807 to 1190 encode the cell wall anchor sequence from the chromosome segregation protein (SEQ ID NO: 22), and nucleotides 1191 to 1193 are the stop codon for translation termination.

[0101] A third exemplary expression cassette for expression of camelid antibodies is: 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 GCTTTGAACA AGGCTAACCA AAAAGTTGCT GATGATACTA CTGCCGTTAA 361 CAACAAACAA ACTGATGTTA ACAATGCAGC AGAAGCTAAG AAGAATGCAG ATGAGGCATT 421 GAAGAACGCC AATGATGCGC AAACTTCTGC ACAAAAGAAT AAAGATGCTA AGCAAGCAAT 481 TGCTGATGAG GCAAGTGTAG AAGTTCAATT AGTTGAAAGT GGTGGTGGTT TAGTTCAACC 541 AGGTGGTAGT TTACGTTTAT CATGTGCTGC AAGTGGTTCA ATTGCAACTA TTAATGATAT 601 GGGTTGGTTT CGTCAAGCAC CAGGAAAGCA ACGTGATTGG GTTGCTACTA TTGTTAGTGA 661 TGGTTCAACT GCTTATGCTG ATAGTGTTAA AGGTCGTTTT ACTATTTCAC GTGATAATGC 721 TAAGAATACT GTTTACCTTC AAATGAATAG TCTTAAGCCA GAAGATACTG CAGTTTACTA 781 TTGTTCAGCT CGTCGTCATT ATGGTCAAGG TACTCAAGTT ACTGTTAGTT CAGCTGCAGC 841 TAGTGGTTCA TTAGAACAAA AATTAATTTC AGAAGAAGAT TTAAATGGTG CAGCTCATCA 901 TCATCATCAT CATGGTGCAG CTGCTGAAAA GGAAGCTAAA GATAATGGCT ACCATATCGA 961 AAATAACCAA GTTGTTGACG CTAAAGGTAA TAGTGTCAAT GGCTGGACAG TTAAGGGCAA 1021 CCAAATTGTT AGTCCAACTA ATGCTACTGT AGATCCCGCT GTTTCTGTAA CCACCAATGT 1081 CAATGTTGAT AGTAAAGGTC AAGTACAACC ACAAACTAGT GTTACTGCTA ATAGTGTTAA 1141 GACTGTAGCT GCAACTGAAT CAGCAAATCC AGTAGCAACT ACTACTGTGC AAACCCGCGA 1201 ACAATACAAG CAACAATTGA AGAGCAATAA TCAATTACCA CAAACTGGTA ATAATGATAG 1261 TGCTGTTCTT TCACTTGCTG GAGTAGCACT TGCAGCAATG TTGAGTTTGT TCGGTATTAA 1321 GAAACGTGAA TACTAATTTA GAAAATGTAA GTATTATTAT GTAAAAAGGT TCAACCAAAT 1381 TGGCTGAACC TTTTTGTCTA AAATTTAAGG AGAAGTTTT (SEQ ID NO: 39), in which nucleotides 1 to 313 represent the promoter sequence derived from the chromosome segregation protein Smc (SEQ ID NO: 43), nucleotides 314 to 499 encode the secretion signal derived from the chromosome segregation protein Smc (SEQ ID NO: 40), nucleotides 500 to 922 encode the VHH EAT-1G4 (SEQ ID NO: 30), nucleotides 923 to 1333 encode the cell wall anchor sequence derived from the chromosome segregation protein Smc (SEQ ID NO: 40), and nucleotides 1334 to 1336 are a stop codon for translation termination.

[0102] Many other combinations of the expression cassette elements of the present disclosure are possible. [Example]

[0103] Bacillus-derived anti-infective molecules. Certain Bacillus strains may also be used as DFMs for poultry, for example. Over 100 Bacillus isolates were collected from the ceca of chickens. The chickens were from Indiana, USA. Isolates were selected to survive 100°C for 10 minutes for development into pellet-stable products. Isolates were confirmed as Bacillus using 16S rRNA sequencing. Isolates were tested for antibacterial activity against various poultry pathogens, including Salmonella Enteritidis, avian pathogenic Escherichia coli, Clostridium perfringens, Enterococcus cecorum, and Campylobacter jejuni. Different isolates exhibit different antibacterial activity against these pathogens. Of all isolates, five were cytotoxic to all pathogens tested. All five isolates were isolated from samples taken from the same study, suggesting that they may possibly be clonal. Two isolates, D24 and D72, were selected for further characterization.

[0104] Two selected isolates (D24 and D72) were sequenced by ILLUMINA® sequencing and determined to be most likely Bacillus velezensis. The genome sequences were analyzed for potential bacteriocins, antimicrobial peptides, and digestive enzymes. These isolates contain several complete genetic loci that may encode antimicrobial peptides and bacteriocins. Considering the feasibility of engineering these antimicrobial peptides and bacteriocins into an L. reuteri expression system, five ribosomal bacteriocins were selected for further study. Based on sequence homology, the five Bacillus bacteriocins were identified as follows: Antimicrobial peptide LCI: AIKPVPSPNGIFAASFELNGTTWIFKYKYYDSSKGYWVGIYESVDK (SEQ ID NO: 44); Circularin A: LASTLGISTAAAKKAIDIIDAASTIASIISLIGIVTGAGAISYAIVATAKTMIKKYGKKYAAAW (SEQ ID NO: 45); Lanthipeptide 3 (Plantaricin C): EFSGGGGAEQRGISQGNDGKLCTLTWECGLCPTHTCWC (SEQ ID NO: 46); Lanthipeptide 5 (Lichenicidin A2): SDATPMTVTPTTITIPISLAGCPTTKCASIVSPCN (SEQ ID NO: 47); and Lanthipeptide 6: SEATPMTVTPTTITIPISLAGCPTTKCASIVSPCND (SEQ ID NO: 47). These bacteriocins have previously been shown to kill a variety of gram-negative and gram-positive pathogens.

[0105] These Bacillus-derived anti-infective peptides may be incorporated into expression cassettes and recombinantly expressed. The recombinant Bacillus-derived anti-infective peptides may be expressed alone or in conjunction with one or more of the following: other anti-infective peptides or phages disclosed in Example 2, lytic enzymes disclosed in Example 6, or antibodies such as those disclosed in Example 7. [Example]

[0106] In vivo effects of L. reuteri The identified strains can function effectively as direct-fed live bacteria only if they are able to colonize the host's gastrointestinal tract. The ability of L. reuteri strains to colonize chickens will be evaluated following different routes of administration.

[0107] L. reuteri is administered orally to 10-day-old chicks. At various times post-inoculation, the chicks are sacrificed and the presence of L. reuteri in the crop, small intestine, and cecum is assessed. Strain 3632 is able to colonize all three tissues and remain detectable for at least 18 days.

[0108] L. reuteri is administered by in ovo inoculation (i.e., injection into eggs) three days before hatch. Strain 3632 is found in chick tissues at 3 and 7 days after hatch, while colonization of the control strain declines after 3 days.

[0109] L. reuteri is administered in ovo by spraying a liquid containing the bacteria onto the surface of the eggs. Strains 3630 and 3632 are also able to establish and are still present in chicks 3 and 7 days after hatch. Inoculation by spray is just as effective as in ovo injection, but reduces the handling required to hatch the eggs.

[0110] Recombinant strains 3630 and 3632 carrying expression cassettes containing one of the antibodies of Example 7 or the PlyCM lytic enzyme are administered by in ovo inoculation. The recombinant strains are able to efficiently colonize the gastrointestinal tract of chickens at levels comparable to the unmodified parental strain. Thus, the genetic manipulations contemplated herein do not alter the ability of the modified strains to act as DFMs.

[0111] Chicks carrying L. reuteri strains or modified strains are evaluated for susceptibility to necrotic enteritis. Chicks are inoculated with live L. reuteri expression systems in which the expression cassette contains either a single chain antibody or a lytic enzyme. Inoculations are performed at 10 8 This is done orally by providing the chicks with drinking water containing the recombinant L. reuteri.

[0112] The experiment was conducted as shown in Table 2, with 40 one-day-old chicks in each of 10 groups. Chicks in group 1 served as untreated, unchallenged controls. Chicks in group 2 served as untreated, challenged controls. Group 3 was challenged with standard antibiotic treatment. Each of groups 2-10 received 2 x 10 chicks on days 17 and 18, respectively. 8Each chick in each treatment group received a CFU of C. perfringens. Groups 4-9 were each vaccinated with L. reuteri continuously from day 1. Group 10 received only a therapeutic dose of L. reuteri from days 18-21. On day 21, the chicks were sacrificed and small intestinal tissue examined for the presence of lesions. Survival of chicks in each treatment group was also recorded.

[0113] As shown in Table 2, each of the four antibodies can ameliorate the disease to some extent. The combination of strains may also be more effective than any one strain.

[0114] [Table 2]

Claims

1. 1. A biodelivery platform comprising a genetically modified microorganism comprising an expression cassette, the expression cassette a promoter for transcriptional expression, a nucleic acid sequence encoding a signal sequence for secretion, a nucleic acid sequence encoding a cell wall anchor; at least one heterologous coding region encoding a desired biomolecule; a nucleic acid sequence encoding an expressible peptide tag for detection; Terminators for translation and transcription termination a biodelivery platform comprising one or more of:

2. 2. The biodelivery platform of claim 1, wherein the genetically modified microorganism is a bacterium selected from the group consisting of Bacillus, Lactobacillus, Lactococcus, and Enterococcus.

3. The biodelivery platform of claim 1 , wherein the genetically modified microorganism is a Lactobacillus reuteri strain.

4. 2. The expression cassette as defined in claim 1, wherein the promoter for transcriptional expression is selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:41, SEQ ID NO:42, and SEQ ID NO:

43.

5. 2. The expression cassette of claim 1, wherein the nucleic acid sequence encoding a signal sequence for secretion encodes at least 20 amino acids, at least 25 amino acids, at least 30 amino acids, at least 35 amino acids, at least 40 amino acids, at least 44 amino acids, at least 50 amino acids, at least 55 amino acids, at least 60 amino acids, or at least 65 amino acids.

6. 2. The expression cassette as defined in claim 1, wherein the nucleic acid sequence encoding a signal sequence for secretion encodes between 20 and 65 amino acids, between 25 and 65 amino acids, or between 25 and 40 amino acids.

7. 7. A nucleic acid sequence encoding a signal sequence for secretion as defined in claim 5 or 6, wherein said signal sequence for secretion comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, and SEQ ID NO:

40.

8. 2. The expression cassette of claim 1, wherein the nucleic acid sequence encoding a cell wall anchor encodes between 100 and 250 amino acids, between 125 and 175 amino acids, or between 125 and 150 amino acids.

9. 9. A nucleic acid sequence encoding a cell wall anchor as defined in claim 8, wherein the cell wall anchor comprises an amino acid sequence selected from the group consisting of SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, and SEQ ID NO:

40.

10. 10. The expression cassette of claim 1, wherein said heterologous coding region encoding a desired biomolecule encodes a biomolecule with anti-infective activity, a probiotic factor, an immunomodulatory factor, or a growth-promoting biomolecule.

11. 11. The biomolecule of claim 10, wherein said anti-infective activity is active against pathogenic bacteria or parasites.

12. 12. The anti-infective activity of claim 11, wherein the parasite is an Eimeria species.

13. 12. The anti-infective activity of claim 11, wherein said pathogenic bacteria is selected from the group consisting of Salmonella, Clostridium, Campylobacter, Staphylococcus, Streptococcus, and Escherichia coli.

14. 11. The biomolecule of claim 10, wherein said anti-infective activity is selected from the group consisting of bactericidal peptides, enzymes, lysins, phages, and antibodies.

15. 15. The biomolecule of claim 14, wherein the bactericidal peptide is a mersacidin-like molecule comprising a sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO:

4.

16. 15. The biomolecule of claim 14, wherein the bactericidal peptide is a Bacillus bacteriocin comprising a sequence selected from the group consisting of SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:

48.

17. 15. The biomolecule of claim 14, wherein the enzyme comprises a sequence selected from the group consisting of SEQ ID NO:5 and SEQ ID NO:

6.

18. 15. The biomolecule of claim 14, wherein the lysin comprises a sequence selected from the group consisting of SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, and SEQ ID NO:

28.

19. 15. The biomolecule of claim 14, wherein the phage comprises a sequence selected from the group consisting of SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:

13.

20. The biomolecule of claim 14, wherein the antibody is a single-chain antibody.

21. 21. The antibody of claim 20, wherein said single chain antibody specifically recognizes a bacterial protein from Clostridium perfringens.

22. 22. The antibody of claim 21, wherein the bacterial protein is C. perfringens alpha toxin or C. perfringens NetB toxin.

23. 21. The single chain antibody of claim 20, wherein said single chain antibody comprises a sequence selected from the group consisting of SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:50, and SEQ ID NO:

34.

24. 11. The biomolecule of claim 10, wherein the probiotic factor is an agglutinin receptor comprising a sequence selected from the group consisting of SEQ ID NO: 9 and SEQ ID NO:

10.

25. An expression cassette comprising a promoter for transcriptional expression and at least one heterologous coding region encoding a desired biomolecule, wherein the desired biomolecule is selected from the group consisting of a bactericidal peptide, an enzyme, a lysin, a phage, and an antibody.

26. 26. The expression cassette of claim 25, wherein the promoter comprises a sequence selected from the group of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 41, SEQ ID NO: 42, and SEQ ID NO:

43.

27. 26. The expression cassette of claim 25, wherein the desired biomolecule comprises a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:50, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, and SEQ ID NO:

48.

28. 26. The expression cassette of claim 25, which is located on a plasmid.

29. 29. The expression cassette of claim 28, wherein the plasmid comprises SEQ ID NO:

8.

30. 26. The expression cassette of claim 25, which is located on a bacterial chromosome.

31. 31. The expression cassette of claim 30, which is inserted into a transposase locus.

32. 31. The expression cassette of claim 30, which is inserted into a uracil phosphoribosyl (UPP) transferase locus.

33. 31. The expression cassette of claim 30, which is inserted into the pyrE locus.

34. 25. A method for reducing pathogenic bacterial colonization in an animal, comprising treating the animal with the biodelivery platform of any one of claims 1-24.

35. 35. The method of claim 34, wherein the animal is an avian, human, or non-human mammal.

36. 35. The method of claim 34, wherein the pathogenic bacteria is selected from the group consisting of Salmonella, Clostridium, Campylobacter, Staphylococcus, Streptococcus, and Escherichia coli.

37. 37. The method of any one of claims 34 to 36, wherein the treatment is administered orally, parenterally, nasally, or mucosally.

38. 37. The method of any one of claims 34 to 36, wherein the animal is an avian and the treatment is administered in ovo.

39. 25. The biodelivery platform of any one of claims 1 to 24 for use in therapy.

40. 25. The biodelivery platform of any one of claims 1 to 24 for use in reducing pathogenic bacterial colonization in an animal.

41. 25. The biodelivery platform of any one of claims 1 to 24 for use in the manufacture of a medicament for reducing pathogenic bacterial colonization in an animal.

42. 34. An expression cassette according to any one of claims 25 to 33 for use in the manufacture of a medicament for reducing the colonisation of an animal with a pathogenic bacterium.

43. An antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NO:29, SEQ ID NO:49, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:34, and SEQ ID NO:

50.

44. 44. The antibody of claim 43, which binds to a toxin produced by Clostridium perfringens.

45. 44. The antibody of claim 43 for use in therapy.

46. 44. The antibody of claim 43 for use in reducing the colonization of an animal with a pathogenic bacterium.

47. 44. The antibody of claim 43 for use in the manufacture of a medicament for reducing the colonization of an animal with a pathogenic bacterium.

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