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18,607
[ "BACKGROUND", ":", "Phages", "infecting", "marine", "picocyanobacteria", "often", "carry", "a", "psbA", "gene", ",", "which", "encodes", "a", "homolog", "to", "the", "photosynthetic", "reaction", "center", "protein", ",", "D1", ".", "Host", "encoded", "D1", "decays", "during", "phage", "infection", "in", "the", "light", ".", "Phage", "encoded", "D1", "may", "help", "to", "maintain", "photosynthesis", "during", "the", "lytic", "cycle", ",", "which", "in", "turn", "could", "bolster", "the", "production", "of", "deoxynucleoside", "triphosphates", "(", "dNTPs", ")", "for", "phage", "genome", "replication", ".", "METHODOLOGY", "/", "PRINCIPAL", "FINDINGS", ":", "To", "explore", "the", "consequences", "to", "a", "phage", "of", "encoding", "and", "expressing", "psbA", ",", "we", "derive", "a", "simple", "model", "of", "infection", "for", "a", "cyanophage", "/", "host", "pair", "--", "cyanophage", "P", "-", "SSP7", "and", "Prochlorococcus", "MED4", "-", "-for", "which", "pertinent", "laboratory", "data", "are", "available", ".", "We", "first", "use", "the", "model", "to", "describe", "phage", "genome", "replication", "and", "the", "kinetics", "of", "psbA", "expression", "by", "host", "and", "phage", ".", "We", "then", "examine", "the", "contribution", "of", "phage", "psbA", "expression", "to", "phage", "genome", "replication", "under", "constant", "low", "irradiance", "(", "25", "microE", "m(-2", ")", "s(-1", ")", ")", ".", "We", "predict", "that", "while", "phage", "psbA", "expression", "could", "lead", "to", "an", "increase", "in", "the", "number", "of", "phage", "genomes", "produced", "during", "a", "lytic", "cycle", "of", "between", "2.5", "and", "4.5", "%", "(", "depending", "on", "parameter", "values", ")", ",", "this", "advantage", "can", "be", "nearly", "negated", "by", "the", "cost", "of", "psbA", "in", "elongating", "the", "phage", "genome", ".", "Under", "higher", "irradiance", "conditions", "that", "promote", "D1", "degradation", ",", "however", ",", "phage", "psbA", "confers", "a", "greater", "advantage", "to", "phage", "genome", "replication", ".", "CONCLUSIONS", "/", "SIGNIFICANCE", ":", "These", "analyses", "illustrate", "how", "psbA", "may", "benefit", "phage", "in", "the", "dynamic", "ocean", "surface", "mixed", "layer", "." ]
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21,141
[ "The", "focus", "of", "this", "study", "is", "on", "development", "of", "vaccines", "using", "filamentous", "phage", "as", "a", "delivery", "vector", "for", "immunogenic", "peptides", ".", "The", "use", "of", "phage", "as", "a", "carrier", "for", "immunogenic", "peptides", "provides", "significant", "benefits", "such", "as", "high", "immunogenicity", ",", "low", "production", "costs", ",", "and", "high", "stability", "of", "phage", "preparations", ".", "However", ",", "introduction", "of", "live", "recombinant", "phage", "into", "the", "environment", "might", "represent", "a", "potential", "ecological", "problem", ".", "This", ",", "for", "example", ",", "may", "occur", "when", "vaccines", "are", "used", "in", "oral", "or", "nasal", "formulations", "in", "field", "conditions", "for", "wild", "and", "feral", "animals", ".", "To", "address", "this", "issue", ",", "comparative", "studies", "of", "antigenic", "properties", "of", "live", "and", "inactivated", "(", "non", "-", "viable", ")", "phage", "were", "accomplished", ".", "Inactivated", "phage", ",", "if", "released", ",", "will", "not", "propagate", "and", "will", "degrade", "as", "any", "other", "protein", ".", "In", "these", "experiments", ",", "a", "model", "phage", "clone", "that", "was", "previously", "selected", "from", "a", "phage", "display", "library", "and", "shown", "to", "stimulate", "production", "of", "anti", "-", "sperm", "antibodies", "with", "contraceptive", "properties", "was", "used", ".", "Multiple", "methods", "of", "phage", "inactivation", "were", "tested", ",", "including", "drying", ",", "freezing", ",", "autoclaving", ",", "heating", ",", "and", "UV", "irradiation", ".", "Under", "studied", "conditions", ",", "heating", "at", "76", "°", "C", "for", "3h", ",", "UV", "irradiation", ",", "and", "autoclaving", "resulted", "in", "complete", "phage", "inactivation", ".", "Phage", "samples", "treated", "by", "heat", "and", "UV", "were", "characterized", "by", "spectrophotometry", "and", "electron", "microscopy", ".", "To", "test", "antigenicity", ",", "live", "and", "inactivated", "phage", "preparations", "were", "injected", "into", "mice", "and", "antibody", "responses", "assayed", "by", "ELISA", ".", "It", "was", "found", "that", "phage", "killed", "by", "heat", "causes", "little", "to", "no", "immune", "responses", ",", "probably", "due", "to", "destruction", "of", "phage", "particles", ".", "In", "contrast", ",", "UV", "-", "inactivated", "phage", "stimulated", "production", "of", "IgG", "serum", "antibodies", "at", "the", "levels", "comparable", "to", "live", "phage", ".", "Thus", ",", "vaccines", "formulated", "to", "include", "UV", "-", "inactivated", "filamentous", "phage", "might", "represent", "environmentally", "safe", "alternatives", "to", "live", "phage", "vaccines", "." ]
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8,632
[ "The", "following", "substructural", "elements", "of", "bacteriophage", "T4", "have", "been", "isolated", "in", "homogeneous", "and", "biologically", "active", "state", ":", "the", "whole", "long", "tail", "fibrils", ",", "distal", "and", "proximal", "halves", "of", "the", "long", "tail", "fibrils", "and", "whiskers", ".", "It", "has", "been", "shown", "that", "during", "the", "infection", "of", "Escherichia", "coli", "with", "T4", "amber", "-", "mutants", "(", "defective", "in", "the", "genes", "coding", "for", "heads", "and", "tails", ")", ",", "the", "major", "part", "of", "distal", "and", "proximal", "fibril", "halves", "found", "within", "the", "cell", "appears", "to", "be", "unassociated", ".", "The", "interaction", "of", "distal", "and", "proximal", "fibril", "halves", "with", "the", "bacteriophage", "particle", "is", "necessary", "for", "the", "whole", "tail", "fibril", "formation", "to", "proceed", "effectively", "." ]
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4,217
[ "A", "rapid", "and", "efficient", "method", "to", "purify", "lambda", "gt11", "DNA", "is", "described", ".", "This", "technique", "involves", "precipitation", "of", "intact", "bacteriophage", "particles", "with", "ammonium", "sulfate", ",", "followed", "by", "phage", "lysis", "with", "sodium", "dodecyl", "sulfate", ",", "proteinase", "K", ",", "and", "alkaline", "treatment", ".", "The", "quality", "of", "DNA", "for", "subsequent", "restriction", "analysis", ",", "infectivity", ",", "subcloning", ",", "and", "radiolabeling", "is", "comparable", "to", "that", "isolated", "by", "cesium", "chloride", "banding", "or", "ion", "exchange", "chromatography", ".", "The", "yield", "of", "the", "phage", "DNA", "is", ",", "however", ",", "two", "to", "eight", "times", "higher", "than", "that", "obtained", "by", "other", "conventional", "methods", "of", "lambda", "gt11", "purification", ".", "Furthermore", "the", "time", "required", "to", "process", "the", "bacteriophage", "lysate", "is", "approximately", "2", "h", "and", "therefore", "more", "rapid", "than", "other", "currently", "used", "methods", "." ]
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32,879
[ "INTRODUCTION", ":", "Ankylosing", "spondylitis", "(", "AS", ")", ",", "a", "chronic", "autoimmune", "disease", ",", "has", "been", "linked", "to", "the", "gut", "bacteriome", ".", "METHODS", ":", "To", "investigate", "the", "characteristics", "of", "the", "gut", "virome", "in", "AS", ",", "we", "profiled", "the", "gut", "viral", "community", "of", "193", "AS", "patients", "and", "59", "healthy", "subjects", "based", "on", "a", "metagenome", "-", "wide", "analysis", "of", "fecal", "metagenomes", "from", "two", "publicly", "available", "datasets", ".", "RESULTS", ":", "AS", "patients", "revealed", "a", "significant", "decrease", "in", "gut", "viral", "richness", "and", "a", "considerable", "alteration", "of", "the", "overall", "viral", "structure", ".", "At", "the", "family", "level", ",", "AS", "patients", "had", "an", "increased", "abundance", "of", "Gratiaviridae", "and", "Quimbyviridae", "and", "a", "decreased", "abundance", "of", "Drexlerviridae", "and", "Schitoviridae", ".", "We", "identified", "1,004", "differentially", "abundant", "viral", "operational", "taxonomic", "units", "(", "vOTUs", ")", "between", "patients", "and", "controls", ",", "including", "a", "higher", "proportion", "of", "AS", "-", "enriched", "Myoviridae", "viruses", "and", "control", "-", "enriched", "Siphoviridae", "viruses", ".", "Moreover", ",", "the", "AS", "-", "enriched", "vOTUs", "were", "more", "likely", "to", "infect", "bacteria", "such", "as", "Flavonifractor", ",", "Achromobacter", ",", "and", "Eggerthellaceae", ",", "whereas", "the", "control", "-", "enriched", "vOTUs", "were", "more", "likely", "to", "be", "Blautia", ",", "Ruminococcus", ",", "Collinsella", ",", "Prevotella", ",", "and", "Faecalibacterium", "bacteriophages", ".", "Additionally", ",", "some", "viral", "functional", "orthologs", "differed", "significantly", "in", "frequency", "between", "the", "AS", "-", "enriched", "and", "control", "-", "enriched", "vOTUs", ",", "suggesting", "the", "functional", "role", "of", "these", "AS", "-", "associated", "viruses", ".", "Moreover", ",", "we", "trained", "classification", "models", "based", "on", "gut", "viral", "signatures", "to", "discriminate", "AS", "patients", "from", "healthy", "controls", ",", "with", "an", "optimal", "area", "under", "the", "receiver", "operator", "characteristic", "curve", "(", "AUC", ")", "up", "to", "0.936", ",", "suggesting", "the", "clinical", "potential", "of", "the", "gut", "virome", "for", "diagnosing", "AS", ".", "DISCUSSION", ":", "This", "work", "provides", "novel", "insight", "into", "the", "AS", "gut", "virome", ",", "and", "the", "findings", "may", "guide", "future", "mechanistic", "and", "therapeutic", "studies", "for", "other", "autoimmune", "diseases", "." ]
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6,669
[ "Each", "member", "of", "a", "group", "of", "8", "patients", "with", "acute", "cholera", "was", "treated", "with", "a", "mixture", "of", "four", "cholera", "bacteriophage", "preparations", "containing", "over", "2", "x", "10(12", ")", "phage", "particles", "/", "ml", ".", "These", "massive", "doses", "were", "intended", "to", "kill", "immediately", "all", "vibrios", "in", "the", "intestine", "by", "\"", "lysis", "from", "without", "\"", ".", "The", "numbers", "of", "Vibrio", "cholerae", "were", "drastically", "reduced", "rapidly", ".", "In", "4", "patients", ",", "V.", "cholerae", "was", "completely", "eliminated", "from", "the", "stools", "early", "in", "the", "treatment", ";", "the", "total", "stool", "volume", "and", "after", "-", "treatment", "of", "diarrhoea", "were", "reduced", "in", "comparison", "with", "a", "control", "group", "but", "were", "higher", "than", "in", "a", "group", "of", "patients", "treated", "with", "tetracycline", ".", "In", "the", "other", "4", "patients", "treated", "with", "phage", ",", "vibrios", "disappeard", "more", "slowly", "from", "the", "stools", "and", "there", "was", "no", "apparent", "clinical", "effect", "of", "the", "phage", ".", "In", "all", "the", "patients", "treated", "with", "phage", ",", "the", "duration", "of", "diarrhoea", "was", "longer", "than", "in", "patients", "in", "a", "control", "group", "who", "excreted", "vibrios", "for", "a", "similar", "length", "of", "time", "although", "the", "stool", "output", "was", "similar", ".", "This", "was", "interpreted", "as", "being", "due", "to", "the", "persistence", "of", "vibrios", "in", "foci", "of", "infection", "in", "the", "upper", "intestine", ".", "It", "is", "concluded", "that", "treatment", "of", "cholera", "with", "massive", "doses", "of", "bacteriophage", "is", "not", "as", "effective", "as", "treatment", "with", "tetracycline", ".", "However", ",", "phage", "can", "selectively", "eliminate", "the", "majority", "of", "vibrios", "without", "affecting", "the", "other", "intestinal", "flora", "and", "without", "any", "apparent", "toxic", "effect", "on", "the", "patient", ".", "Phage", "might", "therefore", "be", "useful", "as", "a", "research", "tool", "." ]
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11,210
[ "φg1e", "is", "a", "temperate", "phage", "of", "the", "Lactobacillus", "strain", "G1e", ".", "The", "phage", "-", "host", "junctions", "attR", "and", "attL", "cloned", "from", "the", "lysogen", "have", "a", "24", "-", "bp", "common", "(", "core", ")", "sequence", "implicated", "in", "recombination", ".", "DNA", "sequencing", "analysis", "of", "a", "5.2", "-", "kbp", "SacI", "fragment", "of", "the", "φg1e", "phage", "genome", "(", "42.5", "kbp", ")", "revealed", "two", "possible", "open", "reading", "frames", "(", "ORF", ")", ",", "xis", "and", "int", ",", "and", "the", "phage", "attachment", "(", "recombination", ")", "site", "(", "attP", ")", ",", "whose", "24", "-", "bp", "sequence", "is", "identical", "to", "the", "core", "sequence", "detected", "in", "attR", "and", "attL.", "The", "deduced", "int", "product", "(", "Int", ")", "is", "a", "basic", "protein", "of", "391", "amino", "acids", "with", "an", "estimated", "pI", "of", "9.70", ",", "and", "significantly", "resembles", "other", "presumed", "integrases", "encoded", "by", "the", "Lactobacillus", "and", "Lactococcus", "phages", "including", "φadh", "and", "φLC3", ",", "as", "well", "as", "the", "Escherichia", "coli", "phages", "such", "as", "lambda", ".", "The", "predicted", "φg1e", "xis", "protein", "(", "Xis", ")", "is", "small", "and", "very", "acidic", "(", "66", "amino", "acids", ";", "pI", "4.55", ")", ",", "and", "shows", "a", "resemblance", "(", "32", "%", "overall", "identity", ")", "with", "a", "putative", "excisionase", "encoded", "by", "the", "Staphylococcus", "phage", "φ11", ".", "The", "φg1e", "Int", "with", "a", "deduced", "molecular", "mass", "of", "45.5", "kDa", "was", "overproduced", "in", "E.", "coli", "cells", ",", "and", "electrophoretically", "analyzed", "." ]
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12,247
[ "Herein", ",", "we", "report", "on", "the", "mutational", "analysis", "of", "a", "70", "-", "amino", "acid", "segment", "(", "region", "1", ",", "residues", "438", "-", "508", ")", "of", "family", "B", "DNA", "polymerase", "from", "the", "thermoacidophilic", "archaeon", "Sulfolobus", "solfataricus", "(", "Sso", "DNA", "pol", ")", ".", "Region", "1", ",", "which", "lies", "between", "the", "Exo", "III", "sequence", "and", "the", "similarity", "motif", "D-", "-SLYP", ",", "connects", "the", "exonuclease", "and", "polymerase", "domains", "of", "Sso", "DNA", "pol", ".", "Two", "C", "-", "terminally", "deleted", "forms", "of", "the", "enzyme", ",", "proteins", "N438", "(", "residues", "1", "-", "438", ")", "and", "N508", "(", "residues", "1", "-", "508", ")", ",", "were", "overproduced", "in", "the", "recombinant", "form", "and", "biochemically", "characterized", ".", "They", "contain", "the", "three", "evolutionarily", "conserved", "Exo", "motifs", ",", "but", "differ", "in", "the", "extent", "of", "the", "C", "-", "terminal", "deletion", ",", "since", "only", "N508", "includes", "region", "1", ".", "Both", "have", "been", "found", "to", "retain", "a", "Mn2", "+", "-dependent", "3'-5", "'", "exonuclease", "activity", ",", "whose", "thermal", "stability", "appears", "to", "be", "increased", "in", "comparison", "to", "that", "of", "the", "full", "-", "sized", "enzyme", ".", "Assays", "for", "processive", "3'-5", "'", "exonuclease", "activity", ",", "carried", "out", "with", "the", "heparin", "trap", "method", "on", "a", "24", "-", "base", "oligonucleotide", ",", "have", "revealed", "that", "protein", "N508", ",", "as", "well", "as", "the", "full", "-", "length", "Sso", "DNA", "pol", ",", "retains", "a", "level", "of", "processivity", "of", "the", "degradative", "function", "substantially", "higher", "than", "that", "for", "protein", "N438", ".", "In", "addition", ",", "six", "site", "-", "specific", "mutations", "have", "been", "introduced", "at", "the", "highly", "conserved", "Y", "-", "GG", "/", "A", "motif", ",", "which", "has", "been", "found", "within", "Sso", "DNA", "pol", "region", "1", ".", "All", "mutant", "proteins", "(", "Lys491Ile", ",", "Tyr495Ser", ",", "Lys496Ile", ",", "Gly497Ala", ",", "and", "Ala498Val", ")", "display", "increased", "processivity", "of", "their", "3'-5", "'", "exonuclease", "activity", ",", "with", "the", "exception", "of", "protein", "Tyr495Phe", ".", "By", "a", "steady", "-", "state", "kinetic", "analysis", "of", "the", "exonucleolytic", "reaction", "on", "a", "24", "-", "base", "oligonucleotide", ",", "the", "above", "site", "-", "specific", "mutations", "have", "been", "found", "to", "affect", "Km", "values", "consistently", "with", "the", "observed", "differences", "in", "the", "processivity", "values", ",", "whereas", "the", "effect", "on", "the", "kcat", "values", "seems", "to", "be", "less", "important", ".", "The", "results", "from", "this", "mutational", "analysis", "indicate", "that", "region", "1", "is", "involved", "in", "determining", "the", "processivity", "of", "the", "proofreading", "function", ",", "directly", "interacting", "with", "the", "nucleic", "acid", "substrate", "." ]
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16,637
[ "AIMS", ":", "The", "aim", "of", "this", "study", "was", "to", "isolate", "and", "characterize", "bacteriophages", "against", "bovine", "Staphylococcus", "aureus", "associated", "with", "mastitis", ".", "METHODS", "AND", "RESULTS", ":", "We", "describe", "the", "isolation", "of", "two", "anti", "-", "staphylococcal", "phages", "namely", "DW2", "and", "CS1", "from", "farmyard", "slurry", ".", "Both", "phages", "were", "characterized", "by", "electron", "microscopy", "and", "restriction", "analysis", "and", "shown", "to", "belong", "to", "the", "Siphoviridae", "family", ".", "CS1", "and", "DW2", "were", "lytic", "for", "representatives", "of", "all", "three", "clonal", "groups", "of", "Irish", "mastitis", "-", "associated", "staphylococci", ".", "These", "phages", "were", "compared", "with", "the", "previously", "characterized", "Myoviridae", "phage", "K.", "Infusion", "of", "a", "cocktail", "of", "all", "three", "phages", "at", "10(8", ")", "PFU", "ml(-1", ")", "into", "live", "cow", "teats", "resulted", "in", "no", "detectable", "increase", "in", "somatic", "cell", "counts", "in", "milks", "indicating", "that", "the", "phages", "did", "not", "irritate", "the", "animal", ".", "CONCLUSION", ":", "Two", "new", "anti", "-", "staphylococcal", "phages", "CS1", "and", "DW2", "were", "isolated", "and", "characterized", "and", "tested", "for", "immunogenicity", "in", "animal", "teats", ".", "SIGNIFICANCE", "AND", "IMPACT", "OF", "THE", "STUDY", ":", "The", "phages", "isolated", "in", "this", "study", "are", "active", "against", "pathogenic", "S.", "aureus", "and", "may", "be", "incorporated", "into", "teat", "-", "dips", "or", "teat", "-", "washes", "as", "a", "non", "-", "antibiotic", "prophylaxis", "against", "staphylococcal", "bovine", "mastitis", "." ]
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1,936
[ "The", "fatty", "acid", "accumulation", "in", "a", "lipid", "emulsion", "broth", "was", "examined", "after", "growth", "of", "S.", "aureus", "strains", "incubated", "for", "18", "hours", "at", "37", "degrees", "C.", "Among", "40", "strains", "from", "acute", "infections", "and", "from", "nasal", "carriers", ",", "Tween", "80", "-", "positive", "staphylococci", "in", "phage", "group", "III", "caused", "accumulation", "of", "significantly", "larger", "amounts", "of", "fatty", "acids", "than", "did", "Tween", "80", "-", "positive", "strains", "in", "phage", "group", "I", "and", "Tween", "80", "-", "negative", "strains", "in", "phage", "groups", "I", "and", "III", ".", "Eight", "out", "of", "17", "S.", "aureus", "strains", "isolated", "from", "chronic", "osteomyelitis", "gave", "rise", "to", "a", "low", "amount", "of", ",", "or", "total", "lack", "of", ",", "fatty", "acids", "in", "the", "lipid", "broth", ".", "Seven", "of", "these", "8", "strains", "were", "isolated", "from", "cases", "showing", "relapse", "after", "intensive", "and", "prolonged", "antibiotic", "treatment", ".", "The", "lipid", "metabolism", "of", "4", "strains", "showing", "fatty", "acid", "accumulation", "in", "lipid", "broth", ",", "ranging", "from", "zero", "to", "the", "highest", "value", "found", "in", "the", "investigation", ",", "was", "further", "studied", ".", "Results", "of", "examination", "of", "lipolytic", "action", "on", "trioleinphospholipid", "and", "incorporation", "of", "14C", "-", "labelled", "oleic", "acid", "suggest", "that", "the", "degree", "of", "accumulation", "of", "fatty", "acids", "in", "lipid", "broth", "depends", "on", "variations", "in", "the", "lipolytic", "activity", "of", "the", "strains", "rather", "than", "on", "differences", "in", "incorporation", "of", "the", "produced", "fatty", "acids", ".", "The", "significance", "of", "fatty", "acid", "accumulation", "is", "discussed", "in", "relation", "to", "the", "prognosis", "of", "chronic", "staphylococcal", "osteomyelitis", "." ]
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31,367
[ "The", "antiviral", "function", "of", "carbon", "dots", "(", "CDots", ")", "with", "visible", "light", "exposure", "was", "evaluated", ",", "for", "which", "the", "model", "bacteriophages", "MS2", "as", "a", "surrogate", "of", "small", "RNA", "viruses", "were", "used", ".", "The", "results", "show", "clearly", "that", "the", "visible", "light", "-", "activated", "CDots", "are", "highly", "effective", "in", "diminishing", "the", "infectivity", "of", "MS2", "in", "both", "low", "and", "high", "titer", "samples", "to", "the", "host", "E.", "coli", "cells", ",", "and", "the", "antiviral", "effects", "are", "dot", "concentration-", "and", "treatment", "time", "-", "dependent", ".", "The", "action", "of", "CDots", "apparently", "causes", "no", "significant", "damage", "to", "the", "structural", "integrity", "and", "morphology", "of", "the", "MS2", "phage", "or", "the", "breakdown", "of", "the", "capsid", "proteins", ",", "but", "does", "result", "in", "the", "protein", "carbonylation", "(", "a", "commonly", "used", "indicator", "for", "protein", "oxidation", ")", "and", "the", "degradation", "of", "viral", "genomic", "RNA", ".", "Mechanistically", "the", "results", "may", "be", "understood", "in", "the", "framework", "of", "photodynamic", "effects", "that", "are", "associated", "with", "the", "unique", "excited", "state", "properties", "and", "processes", "of", "CDots", ".", "Opportunities", "for", "potentially", "broad", "applications", "of", "CDots", "coupled", "with", "visible", "/", "natural", "light", "in", "the", "prevention", "and", "control", "of", "viral", "transmission", "and", "spread", "are", "highlighted", "and", "discussed", "." ]
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27,229
[ "As", "a", "bifunctional", "enzyme", ",", "T4", "polynucleotide", "kinase", "phosphatase", "(", "T4", "PNKP", ")", "catalyzes", "the", "phosphorylation", "of", "5'-hydroxyl", ",", "and", "also", "removes", "the", "terminal", "3'-phosphate", "group", ".", "This", "is", "closely", "related", "to", "the", "restructuring", ",", "replication", ",", "and", "damage", "repair", "of", "nucleic", "acid", ".", "In", "this", "paper", ",", "we", "describe", "a", "new", "method", "for", "the", "sensitive", "detection", "of", "T4", "PNKP", "activity", "based", "on", "the", "isothermal", "EXPonential", "amplification", "reaction", "(", "EXPAR", ")", ".", "T4", "PNKP", "can", "be", "linearly", "assayed", "in", "the", "range", "from", "0.001", "to", "0.01", "U", "mL-1", "with", "a", "detection", "limit", "of", "7.9", "×", "10", "-", "4", "U", "mL-1", ".", "Moreover", ",", "the", "method", "exhibits", "high", "specificity", "and", "sensitivity", "and", "can", "be", "applied", "in", "the", "enzyme", "analysis", "of", "complex", "serum", "samples", ".", "In", "view", "of", "its", "simplicity", "and", "moderate", "experimental", "conditions", ",", "the", "method", "may", "suitable", "for", "use", "in", "a", "commercial", "kit", "for", "the", "analysis", "of", "T4", "PNKP", "activity", "." ]
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22,339
[ "Lactococcal", "siphophages", "from", "the", "936", "and", "P335", "groups", "infect", "the", "Gram", "-", "positive", "bacterium", "Lactococcus", "lactis", "using", "receptor", "binding", "proteins", "(", "RBPs", ")", "attached", "to", "their", "baseplate", ",", "a", "large", "multiprotein", "complex", "at", "the", "distal", "part", "of", "the", "tail", ".", "We", "have", "previously", "reported", "the", "crystal", "and", "electron", "microscopy", "(", "EM", ")", "structures", "of", "the", "baseplates", "of", "phages", "p2", "(", "936", "group", ")", "and", "TP901", "-", "1", "(", "P335", "group", ")", "as", "well", "as", "the", "full", "EM", "structure", "of", "the", "TP901", "-", "1", "virion", ".", "Here", ",", "we", "report", "the", "complete", "EM", "structure", "of", "siphophage", "p2", ",", "including", "its", "capsid", ",", "connector", "complex", ",", "tail", ",", "and", "baseplate", ".", "Furthermore", ",", "we", "show", "that", "the", "p2", "tail", "is", "characterized", "by", "the", "presence", "of", "protruding", "decorations", ",", "which", "are", "related", "to", "adhesins", "and", "are", "likely", "contributed", "by", "the", "major", "tail", "protein", "C", "-", "terminal", "domains", ".", "This", "feature", "is", "reminiscent", "of", "the", "tail", "of", "Escherichia", "coli", "phage", "λ", "and", "Bacillus", "subtilis", "phage", "SPP1", "and", "might", "point", "to", "a", "common", "mechanism", "for", "establishing", "initial", "interactions", "with", "their", "bacterial", "hosts", ".", "Comparative", "analyses", "showed", "that", "the", "architecture", "of", "the", "phage", "p2", "baseplate", "differs", "largely", "from", "that", "of", "lactococcal", "phage", "TP901", "-", "1", ".", "We", "quantified", "the", "interaction", "of", "its", "RBP", "with", "the", "saccharidic", "receptor", "and", "determined", "that", "specificity", "is", "due", "to", "lower", "k(off", ")", "values", "of", "the", "RBP", "/", "saccharidic", "dissociation", ".", "Taken", "together", ",", "these", "results", "suggest", "that", "the", "infection", "of", "L.", "lactis", "strains", "by", "phage", "p2", "is", "a", "multistep", "process", "that", "involves", "reversible", "attachment", ",", "followed", "by", "baseplate", "activation", ",", "specific", "attachment", "of", "the", "RBPs", "to", "the", "saccharidic", "receptor", ",", "and", "DNA", "ejection", "." ]
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8,079
[ "The", "kinetics", "of", "in", "vivo", "expression", "of", "the", "polysialosyl", "(", "K1", ")", "capsular", "antigen", "in", "Escherichia", "coli", "has", "been", "studied", ".", "Growth", "of", "E.", "coli", "K1", "strains", "at", "15", "degrees", "C", "prevents", "K1", "polysaccharide", "synthesis", "(", "F.", "A.", "Troy", "and", "M.", "A.", "McCloskey", ",", "J.", "Biol", ".", "Chem", ".", "254:7377", "-", "7387", ",", "1979", ")", ".", "Synthesis", "is", "reactivated", "in", "cells", "grown", "at", "15", "degrees", "C", "after", "upshift", "to", "37", "degrees", "C.", "The", "early", "expression", "and", "resultant", "morphology", "of", "K1", "capsular", "antigen", "was", "monitored", "in", "temperature", "upshift", "experiments", "by", "using", "electron", "microscopy", ".", "Morphological", "stabilization", "of", "the", "capsule", "was", "achieved", "by", "treatment", "of", "cells", "with", "an", "antiserum", "specific", "for", "the", "alpha", ",", "2", "-", "8", "-", "linked", "polysialosyl", "antigen", ".", "The", "kinetics", "of", "K1", "capsule", "expression", "in", "growing", "cells", "was", "measured", "by", "bacteriophage", "adsorption", "with", "phage", "K1F", ",", "which", "required", "the", "K1", "capsule", "for", "binding", ".", "The", "results", "of", "temperature", "upshift", "experiments", "showed", "that", "capsule", "first", "appeared", "on", "the", "cell", "surface", "after", "10", "min", ".", "Subsequent", "bacteriophage", "binding", "increased", "linearly", "with", "time", "until", "a", "fully", "encapsulated", "state", "was", "reached", "45", "min", "after", "upshift", ".", "The", "initiation", "of", "K1", "capsule", "appearance", "was", "dependent", "on", "protein", "synthesis", "and", "the", "addition", "of", "chloramphenicol", "before", "temperature", "upshift", "prevented", "any", "expression", "of", "the", "K1", "antigen", ".", "Chloramphenicol", "reduced", "the", "rate", "of", "K1", "synthesis", "when", "added", "after", "temperature", "upshift", ".", "We", "conclude", "from", "these", "results", "that", "protein", "synthesis", "is", "a", "prerequisite", "for", "activation", "of", "capsule", "expression", "in", "vivo", ",", "but", "not", "for", "subsequent", "elongation", "of", "polysialosyl", "chains", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 0, 1, 2, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
31,871
[ "A", "lytic", "bacteriophage", "vB_EcoM_DE7", "(", "hereafter", "designated", "DE7", ")", "that", "could", "infect", "donkey", "-", "derived", "Escherichia", "coli", "was", "isolated", ".", "The", "bacteriophage", "was", "examined", "by", "transmission", "electron", "microscopy", ",", "and", "the", "result", "showed", "that", "DE7", "belonged", "to", "the", "family", "Myoviridae", ".", "The", "microbiological", "characterization", "revealed", "that", "DE7", "was", "stable", "over", "a", "broad", "range", "of", "pHs", "(", "3", "∼10", ")", "at", "40", "-", "50", "°", "C", ".", "The", "latent", "period", "was", "10", "min", ",", "and", "the", "burst", "size", "was", "43", "PFUs", "/", "infected", "cell", ".", "The", "whole", "-", "genome", "sequencing", "showed", "that", "DE7", "was", "a", "dsDNA", "virus", "and", "had", "a", "genome", "of", "86,130", "bp", ".", "The", "genome", "contained", "124", "predicted", "open", "reading", "frames", "(", "ORFs", ")", ",", "35", "of", "which", "had", "known", "functions", ",", "including", "DNA", "replication", "and", "modification", ",", "transcriptional", "regulation", ",", "structural", "and", "packaging", "proteins", ",", "and", "host", "cell", "lysis", ".", "Twenty", "tRNA", "genes", "were", "identified", ",", "but", "no", "genes", "associated", "with", "bacterial", "pathogenicity", ",", "lysogeny", "and", "drug", "resistance", "were", "identified", ".", "BLASTN", "analysis", "revealed", "that", "phage", "DE7", "had", "a", "high", "sequence", "identity", "(", "96", "%", ")", "with", "Salmonella", "phage", "vB_SPuM_SP116", ",", "but", "it", "could", "not", "lyse", "any", "Salmonella", "strain", "tested", "in", "this", "study", ".", "DE7", "was", "classified", "as", "a", "Felix", "O1", "-", "like", "virus", "based", "on", "its", "general", "characterization", "and", "genomic", "information", ".", "Since", "phage", "DE7", "exhibited", "high", "efficacy", "in", "lysing", "E.", "coli", "and", "lacked", "genes", "associated", "with", "bacterial", "virulence", ",", "antimicrobial", "resistance", "and", "lysogeny", ",", "it", "could", "be", "potentially", "used", "to", "control", "foal", "diarrhoea", "caused", "by", "E.", "coli", "." ]
[ 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 3, 3, 4, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4 ]
22,841
[ "The", "small", "single", "-", "stranded", "DNA", "(", "ssDNA", ")", "bacteriophages", "of", "the", "subfamily", "Gokushovirinae", "were", "traditionally", "perceived", "as", "narrowly", "targeted", ",", "niche", "-", "specific", "viruses", "infecting", "obligate", "parasitic", "bacteria", ",", "such", "as", "Chlamydia", ".", "The", "advent", "of", "metagenomics", "revealed", "gokushoviruses", "to", "be", "widespread", "in", "global", "environmental", "samples", ".", "This", "study", "expands", "knowledge", "of", "gokushovirus", "diversity", "in", "the", "environment", "by", "developing", "a", "degenerate", "PCR", "assay", "to", "amplify", "a", "portion", "of", "the", "major", "capsid", "protein", "(", "MCP", ")", "gene", "of", "gokushoviruses", ".", "Over", "500", "amplicons", "were", "sequenced", "from", "10", "environmental", "samples", "(", "sediments", ",", "sewage", ",", "seawater", "and", "freshwater", ")", ",", "revealing", "the", "ubiquity", "and", "high", "diversity", "of", "this", "understudied", "phage", "group", ".", "Residue", "-", "level", "conservation", "data", "generated", "from", "multiple", "alignments", "was", "combined", "with", "a", "predicted", "3D", "structure", ",", "revealing", "a", "tendency", "for", "structurally", "internal", "residues", "to", "be", "more", "highly", "conserved", "than", "surface", "-", "presenting", "protein", "-", "protein", "or", "viral", "-", "host", "interaction", "domains", ".", "Aggregating", "this", "data", "set", "into", "a", "phylogenetic", "framework", ",", "many", "gokushovirus", "MCP", "clades", "contained", "samples", "from", "multiple", "environments", ",", "although", "distinct", "clades", "dominated", "the", "different", "samples", ".", "Antarctic", "sediment", "samples", "contained", "the", "most", "diverse", "gokushovirus", "communities", ",", "whereas", "freshwater", "springs", "from", "Florida", "were", "the", "least", "diverse", ".", "Whether", "the", "observed", "diversity", "is", "being", "driven", "by", "environmental", "factors", "or", "host", "-", "binding", "interactions", "remains", "an", "open", "question", ".", "The", "high", "environmental", "diversity", "of", "this", "previously", "overlooked", "ssDNA", "viral", "group", "necessitates", "further", "research", "elucidating", "their", "natural", "hosts", "and", "exploring", "their", "ecological", "roles", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
13,807
[ "Recently", ",", "we", "identified", "a", "neutrophil", "-", "binding", "phage", "displaying", "a", "novel", "peptide", "motif", ",", "GPNLTGRW", ".", "It", "was", "determined", "that", "this", "peptide", ",", "when", "displayed", "on", "bacteriophage", "(", "FGP", "phage", ")", ",", "elicits", "a", "transient", "increase", "in", "cytosolic", "calcium", ".", "Here", ",", "we", "show", "that", "FGP", "phage", "stimulate", "neutrophil", "chemotaxis", "and", "induce", "a", "pertussis", "toxin", "-", "sensitive", "rise", "in", "cytosolic", "calcium", "in", "monocytes", "as", "well", "as", "in", "neutrophils", ".", "In", "contrast", "to", "the", "calcium", "response", "elicited", "by", "classical", "chemoattractants", "fMLP", "and", "IL-8", ",", "the", "FGP", "phage", "-", "elicited", "response", "in", "neutrophils", "is", "dependent", "on", "extracellular", "calcium", "and", "is", "mediated", "by", "receptor", "-", "activated", ",", "divalent", "cation", "channels", ".", "Consistent", "with", "G", "protein", "-", "coupled", "receptor", "signaling", ",", "FGP", "phage", "effect", "homologous", "and", "reciprocal", "heterologous", "desensitization", "with", "fMLP-", "and", "IL-8", "-", "stimulated", "calcium", "responses", ".", "Like", "non", "-", "G", "protein", "-", "coupled", "responses", ",", "the", "FGP", "-", "elicited", "calcium", "transient", "is", "abolished", "with", "phosphoinositide-3", "-", "kinase", "inactivation", ".", "Nonetheless", ",", "specific", "binding", "of", "GTP", "to", "neutrophil", "membranes", "follows", "stimulation", "with", "FGP", "phage", ",", "further", "supporting", "involvement", "of", "G", "proteins", ".", "However", ",", "FGP", "phage", "neither", "bind", "to", "nor", "elicit", "a", "calcium", "response", "from", "transfectant", "cells", "harboring", "known", "candidate", "G", "protein", "-", "coupled", "receptors", ".", "These", "data", "together", "suggest", "that", "the", "elicited", "responses", "are", "mediated", "by", "a", "novel", "G", "protein", "-", "coupled", "receptor", "or", "represent", "novel", "responses", "of", "a", "known", "receptor", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
32,513
[ "CRISPR", "-", "Cas", "are", "prokaryotic", "defence", "systems", "that", "provide", "protection", "against", "invasion", "by", "mobile", "genetic", "elements", "(", "MGE", ")", ",", "including", "bacteriophages", ".", "MGE", "can", "overcome", "CRISPR", "-", "Cas", "defences", "by", "encoding", "anti", "-", "CRISPR", "(", "Acr", ")", "proteins", ".", "These", "proteins", "are", "produced", "in", "the", "early", "stages", "of", "the", "infection", "and", "inhibit", "the", "CRISPR", "-", "Cas", "machinery", "to", "allow", "phage", "replication", ".", "While", "research", "on", "Acr", "has", "mainly", "focused", "on", "their", "discovery", ",", "structure", "and", "mode", "of", "action", ",", "and", "their", "applications", "in", "biotechnology", ",", "the", "impact", "of", "Acr", "on", "the", "ecology", "of", "MGE", "as", "well", "as", "on", "the", "coevolution", "with", "their", "bacterial", "hosts", "only", "begins", "to", "be", "unravelled", ".", "In", "this", "review", ",", "we", "summarise", "our", "current", "understanding", "on", "the", "distribution", "of", "anti", "-", "CRISPR", "genes", "in", "MGE", ",", "the", "ecology", "of", "phages", "encoding", "Acr", ",", "and", "their", "coevolution", "with", "bacterial", "defence", "mechanisms", ".", "We", "highlight", "the", "need", "to", "use", "more", "diverse", "and", "complex", "experimental", "models", "to", "better", "understand", "the", "impact", "of", "anti", "-", "CRISPR", "in", "MGE", "-", "host", "interactions", "." ]
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21,394
[ "It", "is", "well", "appreciated", "that", "the", "evolutionary", "divergence", "of", "genes", "and", "genomes", "from", "a", "common", "ancestor", "ultimately", "leads", "to", "incompatibilities", "if", "those", "genomes", "are", "hybridized", ".", "Far", "less", "is", "known", "about", "the", "ability", "and", "nature", "of", "compensatory", "evolution", "to", "yield", "the", "recovery", "of", "function", "in", "hybrid", "genomes", ".", "Here", "the", "major", "capsid", "gene", "of", "the", "bacteriophage", "T7", "(", "40", "-", "kb", "dsDNA", ")", "was", "replaced", "with", "the", "homologous", "gene", "of", "either", "T3", "or", "K11", ",", "each", "22", "%", "different", "at", "the", "protein", "level", "from", "the", "T7", "homolog", ".", "Initial", "fitness", "was", "moderately", "impaired", "for", "the", "T3", "exchange", ",", "but", "the", "K11", "exchange", "was", "not", "viable", "without", "a", "compensatory", "change", "in", "the", "T7", "scaffolding", "protein", ".", "Subsequent", "adaptation", "of", "the", "transgenic", "phages", "led", "to", "nearly", "complete", "fitness", "recoveries", ".", "Compensatory", "changes", "were", "few", ",", "mostly", "in", "the", "transgene", "and", "its", "main", "interacting", "partner", ",", "the", "scaffolding", "protein", "gene", ".", "The", "large", "magnitude", "of", "fitness", "recovery", "with", "relatively", "few", "mutations", "suggests", "that", "the", "fitness", "costs", "of", "hybridizations", "and", "horizontal", "gene", "exchanges", "between", "moderately", "diverged", "genomes", "can", "potentially", "be", "short", "-", "lived", "through", "compensatory", "evolution", "." ]
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20,599
[ "Phage", "vB_EcoM_CBA120", "(", "CBA120", ")", ",", "isolated", "against", "Escherichia", "coli", "O157", ":", "H7", "from", "a", "cattle", "feedlot", ",", "is", "morphologically", "very", "similar", "to", "the", "classic", "phage", "ViI", "of", "Salmonella", "enterica", "serovar", "Typhi", ".", "Until", "recently", ",", "little", "was", "known", "genetically", "or", "physiologically", "about", "the", "ViI", "-", "like", "phages", ",", "and", "none", "targeting", "E.", "coli", "have", "been", "described", "in", "the", "literature", ".", "The", "genome", "of", "CBA120", "has", "been", "fully", "sequenced", "and", "is", "highly", "similar", "to", "those", "of", "both", "ViI", "and", "the", "Shigella", "phage", "AG3", ".", "The", "core", "set", "of", "structural", "and", "replication", "-", "related", "proteins", "of", "CBA120", "are", "homologous", "to", "those", "from", "T", "-", "even", "phages", ",", "but", "generally", "are", "more", "closely", "related", "to", "those", "from", "T4", "-", "like", "phages", "of", "Vibrio", ",", "Aeromonas", "and", "cyanobacteria", "than", "those", "of", "the", "Enterobacteriaceae", ".", "The", "baseplate", "and", "method", "of", "adhesion", "to", "the", "host", "are", ",", "however", ",", "very", "different", "from", "those", "of", "either", "T4", "or", "the", "cyanophages", ".", "None", "of", "the", "outer", "baseplate", "proteins", "are", "conserved", ".", "Instead", "of", "T4", "'s", "long", "and", "short", "tail", "fibers", ",", "CBA120", ",", "like", "ViI", ",", "encodes", "tail", "spikes", "related", "to", "those", "normally", "seen", "on", "podoviruses", ".", "The", "158", "kb", "genome", ",", "like", "that", "of", "T4", ",", "is", "circularly", "permuted", "and", "terminally", "redundant", ",", "but", "unlike", "T4", "CBA120", "does", "not", "substitute", "hmdCyt", "for", "cytosine", "in", "its", "DNA", ".", "However", ",", "in", "contrast", "to", "other", "coliphages", ",", "CBA120", "and", "related", "coliphages", "we", "have", "isolated", "can", "not", "incorporate", "3H", "-", "thymidine", "(", "3H", "-", "dThd", ")", "into", "their", "DNA", ".", "Protein", "sequence", "comparisons", "cluster", "the", "putative", "\"", "thymidylate", "synthase", "\"", "of", "CBA120", ",", "ViI", "and", "AG3", "much", "more", "closely", "with", "those", "of", "Delftia", "phage", "φW-14", ",", "Bacillus", "subtilis", "phage", "SPO1", ",", "and", "Pseudomonas", "phage", "YuA", ",", "all", "known", "to", "produce", "and", "incorporate", "hydroxymethyluracil", "(", "hmdUra", ")", "." ]
[ 4, 4, 4, 2, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 3, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 0, 4, 0, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 0, 1, 4, 2, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
28,531
[ "Developing", "novel", "antimicrobials", "capable", "of", "controlling", "multidrug", "-", "resistant", "bacterial", "pathogens", "is", "essential", "to", "restrict", "the", "use", "of", "antibiotics", ".", "Bacteriophages", "(", "phages", ")", "constitute", "a", "major", "resource", "that", "can", "be", "harnessed", "as", "an", "alternative", "to", "traditional", "antimicrobial", "therapies", ".", "Phage", "ZCSE2", "was", "isolated", "among", "several", "others", "from", "raw", "sewage", "but", "was", "distinguished", "by", "broad", "-", "spectrum", "activity", "against", "Salmonella", "serovars", "considered", "pathogenic", "to", "humans", "and", "animals", ".", "Lytic", "profiles", "of", "ZCSE2", "against", "a", "panel", "of", "Salmonella", "were", "determined", "together", "with", "low", "temperature", "activity", "and", "pH", "stability", ".", "The", "morphological", "features", "of", "the", "phage", "and", "host", "infection", "processes", "were", "characterized", "using", "a", "combination", "of", "transmission", "electron", "and", "atomic", "force", "microscopies", ".", "Whole", "genome", "sequencing", "of", "ZCSE2", "produced", "a", "complete", "DNA", "sequence", "of", "53,965", "bp", ".", "No", "known", "virulence", "genes", "were", "identified", "in", "the", "sequence", "data", ",", "making", "ZCSE2", "a", "good", "candidate", "for", "phage", "-", "mediated", "biological", "control", "purposes", ".", "ZCSE2", "was", "further", "tested", "against", "S.", "Enteritidis", "in", "liquid", "culture", "and", "was", "observed", "to", "reduce", "the", "target", "bacterium", "to", "below", "the", "limits", "of", "detection", "from", "initial", "concentrations", "of", "107", "-", "108", "Colony", "Forming", "Units", "(", "CFU)/mL.", "With", "a", "broad", "host", "-", "range", "against", "pathogenic", "Salmonella", "serovars", ",", "phage", "ZCSE2", "constitutes", "a", "potential", "tool", "against", "a", "major", "cause", "of", "human", "and", "animal", "disease", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
14,998
[ "Bacteriophage", "Mu", "transposition", "requires", "two", "phage", "-", "encoded", "proteins", ",", "the", "transposase", ",", "Mu", "A", ",", "and", "an", "accessory", "protein", ",", "Mu", "B.", "Mu", "B", "is", "an", "ATP", "-", "dependent", "DNA", "-", "binding", "protein", "that", "is", "required", "for", "target", "capture", "and", "target", "immunity", "and", "is", "an", "allosteric", "activator", "of", "transpososome", "function", ".", "The", "recent", "NMR", "structure", "of", "the", "C", "-", "terminal", "domain", "of", "Mu", "B", "(", "Mu", "B223", "-", "312", ")", "revealed", "that", "there", "is", "a", "patch", "of", "positively", "charged", "residues", "on", "the", "solvent", "-", "exposed", "surface", ".", "This", "patch", "may", "be", "responsible", "for", "the", "nonspecific", "DNA", "binding", "activity", "displayed", "by", "the", "purified", "Mu", "B223", "-", "312", "peptide", ".", "We", "show", "that", "mutations", "of", "three", "lysine", "residues", "within", "this", "patch", "completely", "abolish", "nonspecific", "DNA", "binding", "of", "the", "C", "-", "terminal", "peptide", "(", "Mu", "B223-", "312", ")", ".", "To", "determine", "how", "this", "DNA", "binding", "activity", "affects", "transposition", "we", "mutated", "these", "lysine", "residues", "in", "the", "full", "-", "length", "protein", ".", "The", "full", "-", "length", "protein", "carrying", "all", "three", "mutations", "was", "deficient", "in", "both", "strand", "transfer", "and", "allosteric", "activation", "of", "transpososome", "function", "but", "retained", "ATPase", "activity", ".", "Peptide", "binding", "studies", "also", "revealed", "that", "this", "patch", "of", "basic", "residues", "within", "the", "C", "-", "terminal", "domain", "of", "Mu", "B", "is", "within", "a", "region", "of", "the", "protein", "that", "interacts", "directly", "with", "Mu", "A.", "Thus", ",", "we", "conclude", "that", "this", "protein", "segment", "contributes", "to", "both", "DNA", "binding", "and", "protein", "-", "protein", "contacts", "with", "the", "Mu", "transposase", "." ]
[ 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 2, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4 ]
18,015
[ "Pseudomonas", "aeruginosa", "is", "a", "common", "and", "important", "pathogen", "in", "the", "critically", "ill", ".", "It", "combines", "environmental", "hardiness", "with", "genomic", "plasticity", "and", "is", "well", "adapted", "to", "the", "various", "niches", "available", "in", "the", "intensive", "care", "unit", "(", "ICU", ")", ".", "Unresolved", "arguments", "over", "the", "value", "of", "dual", "versus", "monotherapy", "relate", "primarily", "to", "rapidity", "of", "killing", "and", "to", "the", "avoidance", "of", "therapeutic", "failure", "due", "to", "antibiotic", "resistance", ".", "Increasing", "resistance", "to", "conventional", "antibiotics", "means", "that", "we", "need", "to", "be", "aware", "of", "the", "factors", "that", "promote", "the", "success", "of", "this", "pathogen", "in", "the", "ICU", ",", "and", "of", "emerging", "alternative", "strategies", ".", "This", "review", "focuses", "on", "an", "understanding", "of", "the", "underlying", "issues", "and", "on", "the", "practical", "aspects", "of", "prescribing", ",", "particularly", "in", "the", "ICU", "." ]
[ 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
33,500
[ "Bacteroides", ",", "the", "prominent", "bacteria", "in", "the", "human", "gut", ",", "play", "a", "crucial", "role", "in", "degrading", "complex", "polysaccharides", ".", "Their", "abundance", "is", "influenced", "by", "phages", "belonging", "to", "the", "Crassvirales", "order", ".", "Despite", "identifying", "over", "600", "Crassvirales", "genomes", "computationally", ",", "only", "few", "have", "been", "successfully", "isolated", ".", "Continued", "efforts", "in", "isolation", "of", "more", "Crassvirales", "genomes", "can", "provide", "insights", "into", "phage", "-", "host", "-", "evolution", "and", "infection", "mechanisms", ".", "We", "focused", "on", "wastewater", "samples", ",", "as", "potential", "sources", "of", "phages", "infecting", "various", "Bacteroides", "hosts", ".", "Sequencing", ",", "assembly", ",", "and", "characterization", "of", "isolated", "phages", "revealed", "14", "complete", "genomes", "belonging", "to", "three", "novel", "Crassvirales", "species", "infecting", "Bacteroides", "cellulosilyticus", "WH2", ".", "These", "species", ",", "Kehishuvirus", "sp", ".", "'", "tikkala", "'", "strain", "Bc01", ",", "Kolpuevirus", "sp", ".", "'", "frurule", "'", "strain", "Bc03", ",", "and", "'", "Rudgehvirus", "jaberico", "'", "strain", "Bc11", ",", "spanned", "two", "families", ",", "and", "three", "genera", ",", "displaying", "a", "broad", "range", "of", "virion", "productions", ".", "Upon", "testing", "all", "successfully", "cultured", "Crassvirales", "species", "and", "their", "respective", "bacterial", "hosts", ",", "we", "discovered", "that", "they", "do", "not", "exhibit", "co", "-", "evolutionary", "patterns", "with", "their", "bacterial", "hosts", ".", "Furthermore", ",", "we", "observed", "variations", "in", "gene", "similarity", ",", "with", "greater", "shared", "similarity", "observed", "within", "genera", ".", "However", ",", "despite", "belonging", "to", "different", "genera", ",", "the", "three", "novel", "species", "shared", "a", "unique", "structural", "gene", "that", "encodes", "the", "tail", "spike", "protein", ".", "When", "investigating", "the", "relationship", "between", "this", "gene", "and", "host", "interaction", ",", "we", "discovered", "evidence", "of", "purifying", "selection", ",", "indicating", "its", "functional", "importance", ".", "Moreover", ",", "our", "analysis", "demonstrated", "that", "this", "tail", "spike", "protein", "binds", "to", "the", "TonB", "-", "dependent", "receptors", "present", "on", "the", "bacterial", "host", "surface", ".", "Combining", "these", "observations", ",", "our", "findings", "provide", "insights", "into", "phage", "-", "host", "interactions", "and", "present", "three", "Crassvirales", "species", "as", "an", "ideal", "system", "for", "controlled", "infectivity", "experiments", "on", "one", "of", "the", "most", "dominant", "members", "of", "the", "human", "enteric", "virome", "." ]
[ 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 2, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
10,925
[ "Genetic", "instability", "is", "thought", "to", "be", "responsible", "for", "the", "numerous", "genotypic", "changes", "that", "occur", "during", "neoplastic", "transformation", "and", "metastatic", "progression", ".", "To", "explore", "the", "role", "of", "genetic", "instability", "at", "the", "level", "of", "point", "mutations", "during", "mammary", "tumor", "development", "and", "malignant", "progression", ",", "we", "combined", "transgenic", "mouse", "models", "of", "mutagenesis", "detection", "and", "oncogenesis", ".", "Bitransgenic", "mice", "were", "generated", "that", "carried", "both", "a", "bacteriophage", "lambda", "transgene", "to", "assay", "mutagenesis", "and", "a", "polyomavirus", "middle", "T", "oncogene", ",", "mammary", "gland", "-", "targeted", "expression", "of", "which", "led", "to", "metastatic", "mammary", "adenocarcinomas", ".", "We", "developed", "a", "novel", "assay", "for", "the", "detection", "of", "mutations", "in", "the", "lambda", "transgene", "that", "selects", "for", "phage", "containing", "forward", "mutations", "only", "in", "the", "lambda", "cII", "gene", ",", "using", "an", "hfl-", "bacterial", "host", ".", "In", "addition", "to", "the", "relative", "ease", "of", "direct", "selection", ",", "the", "sensitivity", "of", "this", "assay", "for", "both", "spontaneous", "and", "chemically", "induced", "mutations", "was", "comparable", "to", "the", "widely", "used", "mutational", "target", "gene", ",", "lambda", "lacI", ",", "making", "the", "cII", "assay", "an", "attractive", "alternative", "for", "mutant", "phage", "recovery", "for", "any", "lambda", "-", "based", "mouse", "mutagenesis", "assay", "system", ".", "The", "frequencies", "of", "lambda", "cII-", "mutants", "were", "not", "significantly", "different", "in", "normal", "mammary", "epithelium", ",", "primary", "mammary", "adenocarcinomas", ",", "and", "pulmonary", "metastases", ".", "The", "cII", "mutational", "spectra", "in", "these", "tissues", "consisted", "mostly", "of", "G", "/", "C-->A", "/", "T", "transitions", ",", "a", "large", "fraction", "of", "which", "occurred", "at", "CpG", "dinucleotides", ".", "These", "data", "suggest", "that", ",", "in", "this", "middle", "T", "oncogene", "model", "of", "mammary", "tumor", "progression", ",", "a", "significant", "increase", "in", "mutagenesis", "is", "not", "required", "for", "tumor", "development", "or", "for", "metastatic", "progression", "." ]
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7,728
[ "Several", "species", "of", "DNA", "molecules", "are", "packaged", "into", "lambda", "phage", "heads", "if", "they", "carry", "the", "region", "around", "the", "cohesive", "end", "site", "of", "lambda", "phage", "(", "cos", "lambda", ")", ".", "The", "minimal", "functional", "sequence", "around", "cos", "lambda", "needed", "for", "packaging", "was", "examined", "by", "cloning", "in", "pBR322", ".", "The", "results", "showed", "that", "the", "minimal", "region", "contained", "85", "bp", "around", "cos", "lambda", ";", "45", "bp", "of", "the", "left", "arm", "of", "lambda", "phage", "and", "40", "bp", "of", "the", "right", "arm", ".", "A", "75", "-", "bp", "region", "located", "to", "the", "right", "of", "the", "minimal", "region", "seems", "to", "enhance", "packaging", ".", "A", "223", "-", "bp", "fragment", "containing", "these", "regions", "can", "be", "used", "as", "a", "portable", "element", "for", "plasmid", "DNA", "packaging", "into", "lambda", "phage", "heads", ".", "Plasmid", "ppBest", "322", ",", "a", "derivative", "of", "pBR322", "carrying", "this", "portable", "packager", "and", "both", "amp", "and", "tet", "genes", ",", "was", "constructed", ".", "This", "plasmid", "is", "useful", "for", "cloning", "of", "large", "DNA", "fragments", "." ]
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18,112
[ "This", "unit", "describes", "the", "procedure", "used", "to", "move", "portions", "of", "the", "E.", "coli", "genome", "from", "one", "genetic", "variant", "to", "another", ".", "Fragments", "of", "approximately", "100", "kb", "can", "be", "transferred", "by", "the", "P1", "bacteriophage", ".", "The", "phage", "is", "first", "grown", "on", "a", "strain", "containing", "the", "elements", "to", "be", "moved", ",", "and", "the", "resulting", "phage", "lysate", "is", "used", "to", "infect", "a", "second", "recipient", "strain", ".", "The", "lysate", "will", "contain", "bacterial", "DNA", "as", "well", "as", "phage", "DNA", ",", "and", "genetic", "recombination", ",", "catalyzed", "by", "enzymes", "of", "the", "recipient", "strain", ",", "will", "incorporate", "the", "bacterial", "fragments", "into", "the", "recipient", "chromosome", "." ]
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26,812
[ "In", "the", "marine", "environment", ",", "only", "a", "few", "lytic", "single", "-", "stranded", "DNA", "(", "ssDNA", ")", "phages", "have", "been", "isolated", "and", "characterized", ",", "despite", "the", "fact", "that", "diverse", "ssDNA", "bacteriophages", "have", "been", "discovered", "via", "metagenomic", "studies", ".", "In", "this", "study", ",", "we", "isolated", "and", "characterized", "a", "new", "ssDNA", "phage", ",", "vB_RpoMi", "-", "Mini", ",", "which", "infects", "a", "marine", "bacterium", "Ruegeria", "pomeroyi", "DSS-3", ".", "With", "a", "genome", "size", "of", "4248", "bp", "and", "only", "four", "putative", "open", "reading", "frames", "(", "ORF", ")", ",", "vB_RpoMi", "-", "Mini", "becomes", "the", "smallest", "ssDNA", "phage", "among", "the", "known", "ssDNA", "phage", "isolates", "and", "represents", "the", "DNA", "bacteriophage", "with", "the", "least", "number", "of", "ORFs", ".", "Genome", "-", "wide", "analysis", "reveals", "that", "bacteriophage", "Mini", "is", "distantly", "related", "to", "the", "known", "ssDNA", "phages", "and", "belongs", "to", "an", "unclassified", "ssDNA", "phage", "within", "the", "Microviridae", "family", ".", "The", "presence", "of", "peptidase", "in", "vB_RpoMi", "-", "Mini", "genome", "further", "implies", "that", "horizontal", "gene", "transfer", "could", "be", "an", "important", "driving", "force", "in", "the", "evolution", "of", "ssDNA", "phages", ".", "Bacteriophage", "Mini", "seems", "to", "have", "lost", "the", "spike", "protein", "commonly", "seen", "in", "ssDNA", "phages", ",", "suggesting", "that", "ssDNA", "phage", "can", "be", "more", "diverse", "than", "previously", "thought", ".", "Metagenomic", "analysis", "indicates", "that", "Mini", "-", "like", "phages", "are", "widely", "distributed", "in", "the", "environments", ".", "The", "discovery", "of", "vB_RpoMi", "-", "Mini", "expands", "our", "understanding", "of", "ssDNA", "phages", "in", "nature", ",", "and", "also", "indicates", "our", "dearth", "of", "knowledge", "regarding", "of", "ssDNA", "phages", "." ]
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26,810
[ "OBJECTIVE", ":", "The", "gut", "microbiota", "has", "been", "recognized", "as", "a", "critical", "regulator", "of", "human", "health", ",", "and", "novel", "interventions", "to", "selectively", "modulate", "the", "microbiota", "are", "actively", "being", "sought", ".", "Bacteriophages", "(", "bacterial", "viruses", ")", "have", "the", "potential", "to", "selectively", "eliminate", "specific", "detrimental", "microbes", "while", "enhancing", "beneficial", "microbe", "populations", ".", "The", "Bacteriophage", "for", "Gastrointestinal", "Health", "(", "PHAGE", ")", "study", "aimed", "to", "determine", "the", "safety", "and", "tolerability", "of", "supplemental", "bacteriophage", "consumption", "in", "a", "population", "of", "healthy", "adults", "with", "mild", "to", "moderate", "gastrointestinal", "distress", ".", "METHODS", ":", "The", "PHAGE", "study", "was", "a", "randomized", ",", "double", "-", "blind", ",", "placebo", "-", "controlled", "crossover", "intervention", ".", "Healthy", "adults", "with", "self", "-", "reported", "gastrointestinal", "distress", "were", "recruited", "and", "asked", "to", "consume", "one", "15", "-", "mg", "capsule", "containing", "4", "strains", "of", "bacteriophages", "(", "LH01", "-", "Myoviridae", ",", "LL5", "-", "Siphoviridae", ",", "T4D", "-", "Myoviridae", ",", "and", "LL12", "-", "Myoviridae", ")", "and", "a", "placebo", ",", "each", "for", "28", "days", ".", "Participants", "were", "randomly", "assigned", "to", "the", "starting", "treatment", ",", "which", "was", "followed", "by", "a", "2", "-", "week", "washout", "period", "before", "they", "began", "the", "second", "arm", "of", "the", "intervention", ".", "Primary", "outcome", "measures", "included", "a", "comprehensive", "metabolic", "panel", "and", "gastrointestinal", "health", "questionnaire", ".", "In", "addition", ",", "samples", "were", "collected", "for", "future", "analysis", "of", "several", "secondary", "outcome", "measures", ",", "including", "global", "microbiota", "profiles", ",", "plasma", "lipids", ",", "and", "markers", "of", "local", "and", "systemic", "inflammation", ".", "RESULTS", ":", "Forty", "-", "three", "individuals", "met", "all", "study", "criteria", "and", "consented", "to", "participate", ".", "Of", "these", "participants", ",", "36", "completed", "at", "least", "one", "arm", "of", "the", "trial", "and", "32", "completed", "the", "study", ".", "There", "were", "no", "effects", "of", "treatment", "sequence", "on", "comprehensive", "metabolic", "panel", "outcomes", ",", "but", "there", "were", "1-", "and", "2", "-", "way", "carryover", "effects", "on", "gastrointestinal", "questionnaire", "data", ".", "Levels", "of", "aspartate", "aminotransferase", "significantly", "decreased", "while", "participants", "were", "taking", "the", "treatment", "but", "not", "placebo", ";", "however", ",", "all", "mean", "values", "remained", "within", "clinically", "acceptable", "ranges", ".", "Participants", "also", "reported", "significant", "improvements", "in", "several", "symptoms", "of", "gastrointestinal", "distress", "while", "taking", "both", "the", "treatment", "and", "the", "placebo", ".", "CONCLUSIONS", ":", "Consumption", "of", "therapeutic", "doses", "of", "a", "mixture", "of", "4", "bacteriophages", "was", "both", "safe", "and", "tolerable", "in", "a", "target", "human", "population", "." ]
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10,720
[ "Phages", "lambda", "and", "HK022", "express", "proteins", "N", "and", "Nun", ",", "respectively", ",", "each", "of", "which", "acts", "with", "a", "number", "of", "Escherichia", "coli", "host", "Nus", "factors", "at", "lambda", "NUT", "RNA", "sites", ",", "to", "influence", "transcription", "elongation", ".", "The", "lambda", "nut", "sites", ",", "nearly", "identical", "sequences", "located", "downstream", "of", "the", "early", "promoters", ",", "pL", "and", "pR", ",", "were", "first", "identified", "as", "cis", "-", "acting", "signals", "required", "for", "the", "action", "of", "N", "in", "forming", "termination", "-", "resistant", "transcription", "complexes", ".", "Surprisingly", ",", "the", "Nun", "protein", ",", "resembling", "N", "and", "expressed", "by", "another", "lambdoid", "phage", ",", "HK022", ",", "also", "acts", "with", "Nus", "proteins", "to", "terminate", "specifically", "transcription", "initiating", "at", "pL", "and", "pR", "near", "the", "lambda", "nut", "sites", ".", "Based", "on", "structural", "considerations", "of", "the", "amino", "acid", "sequences", ",", "we", "have", "constructed", "nine", "hybrid", "N", "-", "nun", "genes", "and", "used", "these", "hybrids", "to", "identify", "functional", "regions", "of", "the", "N", "and", "Nun", "proteins", ".", "Three", "classes", "of", "hybrid", "gene", "products", "were", "identified", ":", "(", "1", ")", "those", "that", ",", "like", "N", ",", "support", "antitermination", ",", "(", "2", ")", "those", "that", ",", "like", "Nun", ",", "terminate", "transcription", ",", "and", "(", "3", ")", "those", "that", "block", "N", "action", "but", "do", "not", "terminate", "transcription", ".", "We", "find", "that", ",", "similar", "to", "N", ",", "the", "amino", "-", "terminal", "portion", "of", "Nun", "is", "involved", "in", "RNA", "recognition", ".", "The", "more", "carboxy", "portions", "influence", "transcription", "elongation", ",", "antitermination", "(", "N", ")", "and", "termination", "(", "Nun", ")", ".", "Depending", "on", "the", "derivations", "of", "the", "more", "carboxy", "regions", ",", "hybrids", "with", "either", "the", "N", "or", "Nun", "amino", "portions", "support", "either", "termination", "or", "antitermination", ".", "The", "activity", "of", "a", "hybrid", "protein", "may", "be", "influenced", "by", "the", "host", "strain", "depending", "on", "the", "nature", "of", "the", "rpoC", "locus", ",", "a", "locus", "encoding", "the", "beta", "'", "subunit", "of", "RNA", "polymerase", ".", "One", "of", "the", "hybrid", "proteins", "blocks", "antitermination", "when", "the", "rpoC", "locus", "is", "wild", "-", "type", ".", "The", "same", "hybrid", "in", "the", "presence", "of", "the", "rpoC100", "mutation", ",", "which", "alters", "the", "beta", "'", "subunit", ",", "has", "antitermination", "activity", ".", "This", "result", "supports", "the", "argument", "that", "the", "beta", "'", "subunit", "plays", "an", "essential", "role", "in", "determining", "the", "progress", "of", "transcription", "elongation", "." ]
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23,493
[ "Rapid", "biosynthesis", "is", "key", "to", "the", "success", "of", "bacteria", "and", "viruses", ".", "Highly", "expressed", "genes", "in", "bacteria", "exhibit", "a", "strong", "codon", "bias", "corresponding", "to", "the", "differential", "availability", "of", "tRNAs", ".", "However", ",", "a", "large", "clade", "of", "lambdoid", "coliphages", "exhibits", "relatively", "poor", "codon", "adaptation", "to", "the", "host", "translation", "machinery", ",", "in", "contrast", "to", "other", "coliphages", "that", "exhibit", "strong", "codon", "adaptation", "to", "the", "host", ".", "Three", "possible", "explanations", "were", "previously", "proposed", "but", "dismissed", ":", "(", "1", ")", "the", "phage", "-", "borne", "tRNA", "genes", "that", "reduce", "the", "dependence", "of", "phage", "translation", "on", "host", "tRNAs", ",", "(", "2", ")", "lack", "of", "time", "needed", "for", "evolving", "codon", "adaptation", "due", "to", "recent", "host", "switching", ",", "and", "(", "3", ")", "strong", "strand", "asymmetry", "with", "biased", "mutation", "disrupting", "codon", "adaptation", ".", "Here", ",", "we", "examined", "the", "possibility", "that", "phages", "with", "relatively", "poor", "codon", "adaptation", "have", "poor", "translation", "initiation", "which", "would", "weaken", "the", "selection", "on", "codon", "adaptation", ".", "We", "measured", "translation", "initiation", "by", ":", "(", "1", ")", "the", "strength", "and", "position", "of", "the", "Shine", "-", "Dalgarno", "(", "SD", ")", "sequence", ",", "and", "(", "2", ")", "the", "stability", "of", "the", "secondary", "structure", "of", "sequences", "flanking", "the", "SD", "and", "start", "codon", "known", "to", "affect", "accessibility", "of", "the", "SD", "sequence", "and", "start", "codon", ".", "Phage", "genes", "with", "strong", "codon", "adaptation", "had", "significantly", "stronger", "SD", "sequences", "than", "those", "with", "poor", "codon", "adaptation", ".", "The", "former", "also", "had", "significantly", "weaker", "secondary", "structure", "in", "sequences", "flanking", "the", "SD", "sequence", "and", "start", "codon", "than", "the", "latter", ".", "Thus", ",", "lambdoid", "phages", "do", "not", "exhibit", "strong", "codon", "adaptation", "because", "they", "have", "relatively", "inefficient", "translation", "initiation", "and", "would", "benefit", "little", "from", "increased", "elongation", "efficiency", ".", "We", "also", "provided", "evidence", "suggesting", "that", "phage", "lifestyle", "(", "virulent", "versus", "temperate", ")", "affected", "selection", "intensity", "on", "the", "efficiency", "of", "translation", "initiation", "and", "elongation", "." ]
[ 4, 4, 4, 2, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
32,304
[ "Antibiotic", "resistance", "has", "become", "one", "of", "the", "largest", "pitfalls", "of", "modern", "medicine", ",", "and", "this", "has", "fueled", "the", "search", "for", "a", "safe", "and", "effective", "alternative", ".", "Of", "these", "alternatives", ",", "bacteriophage", "(", "phage", ")", "therapy", "has", "emerged", "as", "a", "potential", "option", "since", "it", "is", "capable", "of", "destroying", "pathogenic", "bacteria", ",", "without", "disrupting", "commensal", "bacterial", "populations", ".", "Although", "numerous", "studies", "have", "shown", "its", "efficacy", "in", "various", "conditions", "such", "as", "dysentery", ",", "sepsis", ",", "and", "meningitis", ",", "very", "little", "research", "has", "focused", "on", "its", "prospective", "usage", "to", "treat", "dermatological", "conditions", ".", "This", "review", "discusses", "the", "emerging", "phage", "therapy", "studies", "surrounding", "infections", "caused", "by", "Cutibacterium", "acnes", "(", "C.", "acnes", ")", ",", "Staphylococcus", "aureus", "(", "S.", "aureus", ")", ",", "Pseudomonas", "aeruginosa", "(", "P.", "aeruginosa", ")", ",", "and", "Klebsiella", "pneumoniae", "(", "K.", "pneumoniae", ")", ".", "Phage", "therapy", "shows", "major", "potential", "for", "future", "usage", "in", "the", "field", "of", "dermatology", ",", "yet", "further", "research", "must", "be", "performed", "to", "assure", "safety", "and", "efficacy", "in", "humans", ".", "J", "Drugs", "Dermatol", ".", "2022;21(12):1311", "-", "1315", ".", "doi:10.36849", "/", "JDD.6638", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 0, 1, 4, 4, 0, 1, 4, 0, 1, 4, 4, 0, 1, 4, 0, 1, 4, 4, 4, 0, 1, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
13,994
[ "Combinatorial", "phage", "peptide", "libraries", "have", "been", "used", "to", "identify", "the", "ligands", "for", "specific", "target", "molecules", ".", "These", "libraries", "are", "also", "useful", "for", "identification", "of", "the", "specific", "substrates", "of", "various", "proteases", ".", "A", "substrate", "phage", "library", "has", "a", "random", "peptide", "sequence", "at", "the", "N", "-", "terminus", "of", "the", "phage", "coat", "protein", "and", "an", "additional", "tag", "sequence", "that", "enables", "attachment", "of", "the", "phage", "to", "an", "immobile", "phase", ".", "When", "these", "libraries", "are", "incubated", "with", "a", "specific", "enzyme", ",", "such", "as", "a", "protease", ",", "the", "uncleaved", "phage", "is", "excluded", "from", "the", "solution", "with", "tag", "-", "binding", "macromolecules", ".", "This", "provides", "a", "novel", "approach", "to", "define", "substrate", "specificity", ".", "The", "aim", "of", "this", "review", "is", "to", "summarize", "recent", "progress", "on", "the", "application", "of", "the", "substrate", "phage", "technique", "to", "identify", "specific", "substrates", "of", "proteolytic", "enzymes", ".", "As", "an", "example", ",", "some", "of", "our", "own", "experimental", "data", "on", "the", "selection", "and", "characterization", "of", "substrate", "sequences", "for", "thrombin", ",", "a", "serine", "protease", ",", "and", "membrane", "type-1", "matrix", "metalloproteinase", "(", "MT1", "-", "MMP", ")", "will", "be", "presented", ".", "Using", "this", "approach", ",", "the", "canonical", "consensus", "substrate", "sequence", "for", "thrombin", "was", "deduced", "from", "the", "selected", "clones", ".", "As", "expected", "from", "the", "collagenolytic", "activity", "of", "MT1", "-", "MMP", ",", "a", "collagen", "-", "like", "sequence", "was", "identified", "in", "the", "case", "of", "MT1", "-", "MMP", ".", "A", "more", "selective", "substrate", "sequence", "for", "MT1", "-", "MMP", "was", "identified", "during", "a", "substrate", "phage", "screen", ".", "The", "delineation", "of", "the", "substrate", "specificity", "of", "proteases", "will", "help", "to", "elucidate", "the", "enzymatic", "properties", "and", "the", "physiological", "roles", "of", "these", "enzymes", ".", "Comprehensive", "screening", "of", "very", "large", "numbers", "of", "potential", "substrate", "sequences", "is", "possible", "with", "substrate", "phage", "libraries", ".", "Thus", ",", "this", "approach", "allows", "novel", "substrate", "sequences", "and", "previously", "unknown", "target", "molecules", "to", "be", "defined", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4 ]
11,143
[ "DNA", "fingerprinting", "can", "be", "used", "to", "detect", "genetic", "rearrangements", "in", "cancer", "that", "may", "be", "associated", "with", "activation", "of", "oncogenes", "and", "inactivation", "of", "tumour", "suppressor", "genes", ".", "We", "have", "developed", "a", "fingerprinting", "strategy", "based", "on", "polymerase", "chain", "reaction", "(", "PCR", ")", "amplification", "of", "genomic", "DNA", "with", "primers", "specific", "for", "the", "Alu", "repeat", "sequences", ",", "which", "are", "highly", "abundant", "in", "the", "human", "genome", ".", "This", "has", "been", "applied", "to", "DNA", "from", "pancreatic", "cancer", "and", "paired", "normal", "samples", "to", "isolate", "and", "identify", "fragments", "of", "genomic", "DNA", "rearranged", "in", "the", "malignant", "cells", ".", "These", "fragments", "have", "been", "sequenced", "and", "used", "as", "probes", "to", "isolate", "hybridising", "clones", "from", "gridded", "bacteriophage", "P1", ",", "phage", "artificial", "chromosome", ",", "and", "cosmid", "libraries", "for", "fluorescent", "in", "situ", "hybridisation", "mapping", "and", "the", "identification", "of", "expressed", "sequences", ".", "Further", "characterisation", "has", "identified", "a", "putative", "novel", "gene", "(", "ART1", ")", "that", "is", "up", "-", "regulated", "specifically", "in", "pancreatic", "cancer", "as", "well", "as", "another", "sequence", "with", "similarity", "to", "genes", "involved", "in", "differentiation", "(", "POU", "domains", ")", ".", "In", "conclusion", ",", "we", "suggest", "that", "Alu", "-", "PCR", "fingerprinting", "may", "be", "a", "useful", "technique", "for", "the", "identification", "of", "genes", "involved", "in", "tumourigenesis", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
13,738
[ "BACKGROUND", ":", "Nuclease", "activity", "is", "thought", "to", "be", "a", "significant", "barrier", "to", "effective", "gene", "delivery", "employing", "synthetic", "vectors", ".", "In", "particular", ",", "the", "lysosomal", "DNase", ",", "DNase", "II", ",", "has", "significant", "access", "to", "plasmid", "DNA", ",", "when", "the", "protective", "condensing", "agent", "has", "been", "shed", ".", "Here", ",", "we", "present", "the", "identification", "of", "a", "peptide", "DNase", "II", "inhibitor", ",", "enabling", "enhanced", "levels", "of", "gene", "delivery", ".", "METHODS", ":", "A", "DNase", "II", "inhibitor", "was", "identified", "by", "phage", "display", "from", "a", "cyclic", ",", "random", "12", "-", "amino", "acid", "library", ".", "Activity", "was", "assayed", "by", "inhibition", "of", "DNase", "II", "degradation", "of", "DNA", ".", "Transfection", "enhancement", "levels", "were", "measured", "over", "a", "range", "of", "DNA", "doses", "with", "CV-1", "and", "MDBK", "cell", "types", "using", "PEI", "and", "cationic", "lipoplexes", "as", "vectors", ".", "RESULTS", ":", "We", "postulated", "that", "a", "DNase", "II", "inhibitor", "would", "enhance", "transfection", "by", "enabling", "a", "larger", "fraction", "of", "plasmid", "DNA", "to", "traffic", "through", "the", "cell", "and", "enter", "the", "nucleus", ".", "Peptides", "based", "on", "the", "selected", "sequence", "(", "SLRLLQWFLWAC", ")", "[", "ID2", "]", "were", "shown", "to", "inhibit", "DNase", "II", "with", "an", "observed", "KI", ",", "app", "of", "0.2", "-", "2", "microM.", "Lipoplex", "-", "mediated", "transfection", "in", "vitro", "was", "found", "to", "be", "enhanced", "by", "ID2", "-", "3", "across", "the", "entire", "range", "of", "plasmid", "DNA", "doses", "examined", "(", "0.10", "-", "3.0", "microg", "/", "mL", ")", ".", "Transfection", "with", "PEI", "/", "DNA", "complexes", "was", "found", "to", "be", "specifically", "enhanced", "in", "the", "presence", "of", "ID2", "peptides", ",", "with", "a", "saturable", "DNA", "-", "dose", "curve", "as", "would", "be", "expected", "for", "a", "competitive", "inhibitor", ".", "Transfection", "enhancements", "as", "high", "as", "270", "-", "fold", "were", "found", "in", "the", "presence", "of", "ID2", "-", "3", ".", "CONCLUSIONS", ":", "A", "novel", "peptide", "DNase", "II", "inhibitor", "has", "been", "used", "to", "increase", "transfection", ".", "The", "level", "of", "enhancement", "was", "found", "to", "be", "significant", "in", "multiple", "cell", "types", "with", "multiple", "synthetic", "vectors", "." ]
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29,998
[ "The", "phages", "that", "infect", "Staphylococcus", "species", "are", "dominant", "residents", "of", "the", "skin", "microbiome", "that", "play", "critical", "roles", "in", "health", "and", "disease", ".", "While", "temperate", "phages", ",", "which", "can", "integrate", "into", "the", "host", "genome", ",", "have", "the", "potential", "to", "promote", "staphylococcal", "pathogenesis", ",", "the", "strictly", "lytic", "variety", "are", "powerful", "antimicrobials", "that", "are", "being", "exploited", "for", "therapeutic", "applications", ".", "This", "article", "reviews", "recent", "insights", "into", "the", "diversity", "of", "staphylococcal", "phages", "and", "newly", "described", "mechanisms", "by", "which", "they", "influence", "host", "pathogenicity", ".", "The", "latest", "efforts", "to", "harness", "these", "viruses", "to", "eradicate", "staphylococcal", "infections", "are", "also", "highlighted", ".", "Decades", "of", "research", "has", "focused", "on", "the", "temperate", "phages", "of", "Staphylococcus", "aureus", "as", "model", "systems", ",", "thus", "underscoring", "the", "need", "to", "broaden", "basic", "research", "efforts", "to", "include", "diverse", "phages", "that", "infect", "other", "clinically", "relevant", "Staphylococcus", "species", "." ]
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7,075
[ "The", "ARCAT", "(", "A", "Rapid", "Coliphage", "Analysis", "Technique", ")", "method", "for", "detecting", "coliphages", "in", "water", "has", "been", "modified", ".", "Modifications", "to", "the", "original", "method", "include", "media", "optimization", ",", "the", "use", "of", "frozen", "host", "cultures", ",", "the", "use", "of", "a", "single", "agar", "coliphage", "assay", "and", "optimized", "plaque", "resolution", "with", "2", ",", "3", ",", "4", "-", "triphenyltetrazolium", "chloride", ".", "Detection", "of", "5", "coliphages", "per", "100", "ml", "of", "water", "sample", "is", "accomplished", "in", "6", "hours", "for", "rapid", "estimation", "of", "water", "quality", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
19,540
[ "Heterozygous", "truncating", "mutations", "in", "CXCR4", "have", "been", "identified", "as", "a", "cause", "of", "WHIM", "syndrome", "(", "warts", ",", "hypogammaglobulinemia", ",", "immunodeficiency", "and", "myelokathexis", ")", ".", "The", "receptor", "truncations", "have", "been", "proposed", "to", "lead", "to", "altered", "lymphocyte", "trafficking", ".", "The", "purpose", "of", "the", "described", "studies", "was", "to", "characterize", "the", "B", "-", "cell", "repertoire", "in", "WHIM", "subjects", ".", "We", "confirmed", "profound", "B", "-", "cell", "lymphopenia", "and", "demonstrated", "oligoclonality", "of", "the", "circulating", "B", "-", "cell", "pool", "by", "HCDR3", "spectratyping", ".", "The", "response", "to", "immunization", "was", "studied", "in", "one", "subject", "utilizing", "a", "bacteriophage", "PhiX174", "immunization", "protocol", ".", "Spectratyping", "showed", "oligoclonality", "at", "baseline", "with", "normalization", "of", "the", "HCDR3", "length", "distribution", "by", "5", "months", "after", "immunization", "with", "PhiX174", "with", "eventual", "return", "to", "the", "baseline", "state", ".", "Isotype", "switching", "from", "phage", "specific", "neutralizing", "antibody", "of", "the", "IgM", "class", "to", "IgG", "was", "markedly", "reduced", ".", "Overall", ",", "these", "data", "suggest", "that", "impaired", "CXCR4", "signaling", "in", "WHIM", "syndrome", "results", "in", "defective", "B", "-", "cell", "function", "and", "abnormal", "isotype", "switching", ",", "possibly", "through", "effects", "on", "germinal", "center", "trafficking", "of", "lymphocytes", "." ]
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13,617
[ "The", "structural", "and", "catalytic", "properties", "of", "the", "phage", "T4", "DNA-(adenine", "-", "N6)-methyltransferase", "(", "EC", "2.1.1.72", ")", "were", "studied", "at", "different", "enzyme", "-", "substrate", "concentration", "ratios", "by", "chemical", "cross", "-", "linking", "of", "the", "protein", "subunits", "and", "by", "measuring", "the", "presteady", "state", "kinetics", "of", "the", "reactions", ".", "Various", "structural", "states", "of", "the", "methyltransferase", "were", "correlated", "with", "its", "catalytic", "activity", ",", "and", "it", "was", "shown", "that", "the", "oligomeric", "forms", "of", "the", "enzyme", "are", "catalytically", "active", "but", "are", "characterized", "by", "the", "reaction", "parameters", "different", "from", "those", "of", "the", "monomer", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
30,135
[ "Pseudomonas", "aeruginosa", "is", "a", "Gram", "-", "negative", "pathogen", "that", "causes", "a", "variety", "of", "infections", "in", "humans", "and", "animals", ".", "Due", "to", "the", "inappropriate", "use", "of", "antibiotics", ",", "multi", "-", "drug", "resistant", "(", "MDR", ")", "P.", "aeruginosa", "strains", "have", "emerged", "and", "are", "prevailing", ".", "In", "recent", "years", ",", "cow", "mastitis", "caused", "by", "MDR", "P.", "aeruginosa", "has", "attracted", "attention", ".", "In", "this", "study", ",", "a", "microbial", "community", "analysis", "revealed", "that", "P.", "aeruginosa", "could", "be", "a", "cause", "of", "pathogen", "-", "induced", "cow", "mastitis", ".", "Five", "MDR", "P.", "aeruginosa", "strains", "were", "isolated", "from", "milk", "diagnosed", "as", "mastitis", "positive", ".", "To", "seek", "an", "alternative", "antibacterial", "agent", "against", "MDR", ",", "P.", "aeruginosa", ",", "a", "lytic", "phage", ",", "designated", "vB_PaeS_PAJD-1", "(", "PAJD-1", ")", ",", "was", "isolated", "from", "dairy", "farm", "sewage", ".", "PAJD-1", "was", "morphologically", "classified", "as", "Siphoviridae", "and", "was", "estimated", "to", "be", "about", "57.9", "kb", ".", "Phage", "PAJD-1", "showed", "broad", "host", "ranges", "and", "a", "strong", "lytic", "ability", ".", "A", "one", "-", "step", "growth", "curve", "analysis", "showed", "a", "relatively", "short", "latency", "period", "(", "20", "min", ")", "and", "a", "relatively", "high", "burst", "size", "(", "223", "PFU", "per", "infected", "cell", ")", ".", "Phage", "PAJD-1", "remained", "stable", "over", "wide", "temperature", "and", "pH", "ranges", ".", "Intramammary", "-", "administered", "PAJD-1", "reduced", "bacterial", "concentrations", "and", "repaired", "mammary", "glands", "in", "mice", "with", "mastitis", "induced", "by", "MDR", "P.", "aeruginosa", ".", "Furthermore", ",", "the", "cell", "wall", "hydrolase", "(", "termed", "endolysin", ")", "from", "phage", "PAJD-1", "exhibited", "a", "strong", "bacteriolytic", "and", "a", "wide", "antibacterial", "spectrum", "against", "MDR", "P.", "aeruginosa", ".", "These", "findings", "present", "phage", "PAJD-1", "as", "a", "candidate", "for", "phagotherapy", "against", "MDR", "P.", "aeruginosa", "infection", "." ]
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21,860
[ "AIM", ":", "ΦC31", "integrase", "mediates", "site", "-", "specific", "recombination", "between", "two", "short", "sequences", ",", "attP", "and", "attB", ",", "in", "phage", "and", "bacterial", "genomes", ",", "which", "is", "a", "promising", "tool", "in", "gene", "regulation", "-", "based", "therapy", "since", "the", "zinc", "finger", "structure", "is", "probably", "the", "DNA", "recognizing", "domain", "that", "can", "further", "be", "engineered", ".", "The", "aim", "of", "this", "study", "was", "to", "screen", "potential", "pseudo", "att", "sites", "of", "ΦC31", "integrase", "in", "the", "human", "genome", ",", "and", "evaluate", "the", "risks", "of", "its", "application", "in", "human", "gene", "therapy", ".", "METHODS", ":", "TFBS", "(", "transcription", "factor", "binding", "sites", ")", "were", "found", "on", "the", "basis", "of", "reported", "pseudo", "att", "sites", "using", "multiple", "motif", "-", "finding", "tools", ",", "including", "AlignACE", ",", "BioProspector", ",", "Consensus", ",", "MEME", ",", "and", "Weeder", ".", "The", "human", "genome", "with", "the", "proposed", "motif", "was", "scanned", "to", "find", "the", "potential", "pseudo", "att", "sites", "of", "ΦC31", "integrase", ".", "RESULTS", ":", "The", "possible", "recognition", "motif", "of", "ΦC31", "integrase", "was", "identified", ",", "which", "was", "composed", "of", "two", "co", "-", "occurrence", "conserved", "elements", "that", "were", "reverse", "complement", "to", "each", "other", "flanking", "the", "core", "sequence", "TTG", ".", "In", "the", "human", "genome", ",", "a", "total", "of", "27924", "potential", "pseudo", "att", "sites", "of", "ΦC31", "integrase", "were", "found", ",", "which", "were", "distributed", "in", "each", "human", "chromosome", "with", "high", "-", "risk", "specificity", "values", "in", "the", "chromosomes", "16", ",", "17", ",", "and", "19", ".", "When", "the", "risks", "of", "the", "sites", "were", "evaluate", "more", "rigorously", ",", "53", "hits", "were", "discovered", ",", "and", "some", "of", "them", "were", "just", "the", "vital", "functional", "genes", "or", "regulatory", "regions", ",", "such", "as", "ACYP2", ",", "AKR1B1", ",", "DUSP4", ",", "etc", ".", "CONCLUSION", ":", "The", "results", "provide", "clues", "for", "more", "comprehensive", "evaluation", "of", "the", "risks", "of", "using", "ΦC31", "integrase", "in", "human", "gene", "therapy", "and", "for", "drug", "discovery", "." ]
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25,943
[ "Bacteria", "and", "bacteriophages", "coexist", "and", "coevolve", ",", "bacteriophages", "being", "obligatory", "predators", "exerting", "an", "evolutionary", "pressure", "on", "their", "prey", ".", "Mechanisms", "in", "action", "vary", "depending", "on", "the", "bacterial", "genomic", "content", "and", "on", "the", "regulation", "of", "the", "bacteriophage", "cycle", ".", "To", "assess", "the", "multiplicity", "of", "bacterial", "genes", "involved", "in", "resistance", "as", "well", "as", "the", "changes", "in", "the", "bacteriophage", "interactions", "with", "the", "bacteria", ",", "it", "is", "necessary", "to", "isolate", "and", "investigate", "large", "numbers", "of", "independent", "resistant", "variants", ".", "Here", "we", "describe", "protocols", "that", "have", "been", "applied", "to", "the", "study", "of", "Pseudomonas", "aeruginosa", "and", "four", "of", "its", "virulent", "bacteriophages", "belonging", "to", "the", "Podoviridae", "and", "Myoviridae", "bacteriophage", "families", ".", "Mutations", "are", "identified", "using", "whole", "genome", "sequencing", "of", "resistant", "variants", ".", "Phenotypic", "analyses", "are", "performed", "to", "describe", "the", "changes", "conferred", "by", "the", "mutations", "." ]
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6,057
[ "The", "relationship", "of", "DNA", "replication", "to", "the", "control", "of", "early", "enzyme", "synthesis", "and", "the", "formation", "of", "late", "proteins", "was", "studied", "in", "protoplasts", "of", "E.", "coli", "B", "cells", "infected", "with", "an", "amber", "mutant", ",", "T4am130", ".", "In", "this", "phage", "-", "host", "system", "the", "bacterial", "DNA", "is", "not", "completely", "degraded", ",", "and", "the", "onset", "and", "the", "extent", "of", "phage", "DNA", "synthesis", "could", "be", "regulated", "by", "use", "of", "5", "-", "fluorodeoxyuridine", "and", "thymidine", ".", "It", "was", "found", "that", "DNA", "replication", "is", "necessary", "for", "the", "transcription", "of", "\"", "late", "\"", "regions", "of", "the", "phage", "genome", "and", ",", "thus", ",", "for", "the", "synthesis", "of", "late", "proteins", ".", "In", "addition", ",", "the", "sustained", "synthesis", "of", "late", "RNA", "and", "the", "tail", "-", "fiber", "protein", "was", "shown", "to", "require", "the", "continued", "replication", "of", "DNA", ".", "Furthermore", ",", "the", "mechanism", "regulating", "the", "cessation", "of", "early", "enzyme", "synthesis", "appeared", "to", "become", "operative", "shortly", "after", "the", "onset", "of", "DNA", "replication", "and", "required", "a", "limited", "amount", "of", "DNA", "synthesis", "for", "its", "full", "expression", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
31,800
[ "Biofilm", "formation", "at", "the", "level", "of", "a", "wound", "plays", "an", "important", "role", "in", "its", "chronicization", ".", "The", "difficulty", "of", "its", "eradication", "has", "driven", "research", "toward", "the", "discovery", "and", "synthesis", "of", "new", "molecules", "that", "can", "act", "on", "biofilm", "to", "promote", "wound", "healing", ".", "This", "narrative", "review", "focuses", "on", "alternative", "molecules", "that", "can", "act", "and", "promote", "the", "eradication", "of", "methicillin", "-", "resistant", "Staphylococcus", "aureus", ",", "taking", "into", "consideration", "its", "antibiotic", "resistance", ",", "virulence", ",", "tendency", "toward", "the", "tenacious", "colonization", "of", "wounds", "by", "biofilms", ",", "and", "its", "increased", "prevalence", "in", "both", "community", "and", "hospital", "settings", ".", "A", "selection", "of", "promising", "studies", "were", "reported", ",", "analyzing", "the", "in", "vitro", "and/or", "in", "vivo", "efficacy", "of", "bacteriophages", ",", "metal", "nanoparticles", ",", "RNAIII", "inhibiting", "peptide", "(", "RIP", ")", ",", "synthetized", "RIP", "derivatives", ",", "proteinase", "K", "and", "hamamelitannin", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
895
[ "Plasmolysed", "cells", "of", "Escherichia", "coli", "N212", "(", "uvr", "A", "recA", ")", "acquired", "ultraviolet", "resistance", "when", "the", "cells", "were", "exposed", "to", "high", "concentrations", "of", "T4", "endonuclease", "V.", "With", "increasing", "concentrations", "of", "T4", "enzyme", ",", "survivals", "of", "plasmolysed", "cells", "after", "ultraviolet", "irradiation", "increased", "while", "colony", "-", "forming", "ability", "of", "unirradiated", "plasmolysed", "cells", "was", "not", "significantly", "affected", "by", "the", "enzyme", "treatment", ".", "Under", "appropriate", "conditions", "more", "than", "200", "fold", "increase", "in", "survivals", "was", "observed", ".", "When", "plasmolysed", "cells", "were", "treated", "with", "a", "pre", "-", "heated", "enzyme", "preparation", "or", "enzyme", "fractions", "derived", "from", "T4v1", "(", "endonuclease", "V", "-", "deficient", "mutant)-infected", "cells", ",", "only", "little", "or", "no", "reactivation", "took", "place", ".", "Permeabilization", "of", "cells", "prior", "to", "the", "enzyme", "treatment", "was", "essential", "for", "the", "effective", "reactivation", ".", "Treatment", "of", "intact", "cells", "with", "the", "T4", "enzyme", "did", "not", "cause", "any", "reactivation", ".", "Cells", "treated", "with", "20", "mM", "EGTA", "or", "50", "mM", "CaCl2", "in", "cold", "were", "reactivated", "to", "certain", "extents", "by", "the", "enzyme", ",", "but", "the", "extents", "of", "the", "reactivation", "were", "far", "less", "compared", "to", "those", "of", "plasmolysed", "cells", ".", "Plasmolysed", "cells", "of", "strains", "carrying", "a", "mutation", "in", "one", "of", "uvrA", ",", "uvrB", "and", "uvrC", "genes", "were", "reactivated", "by", "introduction", "of", "T4", "endonuclease", "V", ",", "as", "was", "the", "uvrA", "recA", "double", "mutant", ".", "UvrD", "mutants", "were", "also", "reactivated", ",", "but", "rather", "slightly", ".", "However", ",", "wild", "type", "strain", "as", "well", "as", "strains", "having", "a", "mutation", "in", "recA", "or", "polA", "gene", "were", "not", "reactivated", ".", "From", "these", "results", "it", "was", "suggested", "that", "T4", "endonuclease", "V", ",", "taken", "up", "into", "permeable", "cells", ",", "can", "function", "in", "vivo", "to", "replace", "defective", "functions", ",", "which", "are", "controlled", "by", "the", "uvr", "genes", ".", "The", "conditions", "established", "in", "the", "present", "study", "may", "be", "used", "for", "introduction", "of", "other", "proteins", "into", "viable", "bacterial", "cells", "." ]
[ 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
26,546
[ "The", "visualization", "of", "viral", "particles", "only", "became", "possible", "after", "the", "advent", "of", "the", "electron", "microscope", ".", "The", "first", "bacteriophage", "images", "were", "published", "in", "1940", "and", "were", "soon", "followed", "by", "many", "other", "publications", "that", "helped", "to", "elucidate", "the", "structure", "of", "the", "particles", "and", "their", "interaction", "with", "the", "bacterial", "hosts", ".", "As", "sample", "preparation", "improved", "and", "new", "technologies", "were", "developed", ",", "phage", "imaging", "became", "important", "approach", "to", "morphologically", "classify", "these", "viruses", "and", "helped", "to", "understand", "its", "importance", "in", "the", "biosphere", ".", "In", "this", "review", "we", "discuss", "the", "main", "milestones", "in", "phage", "imaging", ",", "how", "it", "affected", "our", "knowledge", "on", "these", "viruses", "and", "recent", "developments", "in", "the", "field", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
9,482
[ "BACKGROUND", ":", "Many", "site", "-", "specific", "recombinases", "act", "by", "forming", "and", "resolving", "branched", "Holliday", "junction", "intermediates", ".", "Previous", "findings", "have", "been", "consistent", "with", "models", "involving", "branch", "migration", "across", "the", "'", "overlap", "region", "'", "of", "obligate", "homology", ",", "located", "between", "the", "staggered", "sites", "where", "the", "two", "single", "-", "strand", "exchanges", "occur", ".", "We", "have", "investigated", "the", "validity", "of", "such", "models", "in", "the", "case", "of", "bacteriophage", "lambda", "site", "-", "specific", "recombination", ".", "RESULTS", ":", "By", "using", "synthetic", "lambda", "att", "-", "site", "Holliday", "junctions", ",", "incorporating", "sequence", "heterologies", "that", "impose", "constraints", "on", "branch", "migration", ",", "we", "have", "found", "that", "the", "optimal", "position", "of", "the", "junction", "for", "either", "top", "-", "strand", "or", "bottom", "-", "strand", "resolution", "by", "lambda", "integrase", "(", "Int", ")", "is", "not", "at", "the", "ends", ",", "but", "close", "to", "the", "middle", "of", "the", "seven", "base", "-", "pair", "overlap", "region", ".", "A", "minor", "shift", "of", "the", "branch", "point", "around", "the", "central", "base", "pair", "caused", "a", "remarkable", "switch", "in", "resolution", "bias", ".", "Our", "findings", "suggest", "that", "branch", "migration", "is", "limited", "to", "the", "central", "one", "to", "three", "base", "pairs", "of", "the", "overlap", "region", ".", "They", "lead", "to", "a", "new", "model", "for", "lambda", "site", "-", "specific", "recombination", ",", "in", "which", "there", "are", "two", "symmetrical", "swaps", "of", "two", "to", "three", "nucleotides", "each", ",", "linked", "by", "a", "central", "isomerization", "step", "that", "causes", "a", "change", "of", "the", "stacking", "interactions", "between", "the", "four", "junction", "arms", ".", "On", "the", "basis", "of", "isolated", "strand", "-", "joining", "reactions", "carried", "out", "by", "Int", "in", "the", "presence", "or", "absence", "of", "base", "complementarity", ",", "we", "propose", "that", "sequence", "homology", "is", "sensed", "during", "the", "annealing", "step", "prior", "to", "strand", "joining", ".", "The", "new", "model", "eliminates", "mechanistic", "complications", "associated", "with", "large", "helical", "rotations", "required", "by", "branch", "-", "migration", "models", ".", "CONCLUSIONS", ":", "The", "results", "reported", "here", "suggest", "that", "the", "recognition", "of", "sequence", "homology", "in", "Int", "-", "dependent", "site", "-", "specific", "recombination", "does", "not", "rely", "primarily", "on", "branch", "migration", ".", "The", "property", "of", "cleaving", "Holliday", "junctions", "a", "few", "base", "pairs", "away", "from", "the", "crossover", "puts", "lambda", "Int", "into", "the", "same", "category", "as", "endonucleases", "that", "cleave", "Holliday", "junctions", "in", "homologous", "recombination", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4 ]
4,507
[ "The", "highly", "directional", "site", "-", "specific", "recombination", "of", "bacteriophage", "lambda", "is", "tightly", "regulated", "by", "the", "binding", "of", "three", "different", "proteins", "to", "a", "complex", "array", "of", "sites", ".", "The", "manner", "in", "which", "these", "reactions", "are", "both", "stimulated", "and", "inhibited", "by", "co", "-", "operative", "binding", "of", "proteins", "to", "specific", "sites", "on", "the", "P", "arm", "of", "attP", "and", "AttR", "has", "been", "elucidated", "by", "correlation", "of", "nuclease", "protection", "with", "recombination", "studies", "of", "both", "wild", "-", "type", "and", "mutant", "DNAs", ".", "In", "addition", "to", "co", "-", "operative", "forces", ",", "there", "is", "a", "specific", "competitive", "interaction", "that", "allows", "the", "protein", "-", "DNA", "complex", "to", "serve", "as", "a", "\"", "biological", "switch", "\"", ".", "This", "switch", "does", "not", "depend", "upon", "the", "simple", "occlusion", "of", "DNA", "binding", "sites", "by", "neighboring", "proteins", ";", "but", ",", "rather", ",", "the", "outcome", "of", "this", "competition", "is", "dependent", "on", "long", "-", "range", "interactions", "that", "vary", "between", "the", "higher", "-", "order", "structures", "of", "attP", "and", "attR.", "These", "higher", "-", "order", "structures", "are", "dependent", "on", "cooperative", "interactions", "involving", "three", "proteins", "binding", "to", "five", "or", "more", "sites", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
3,391
[ "A", "fusion", "between", "the", "genes", "encoding", "the", "Escherichia", "coli", "STb", "heat", "-", "stable", "enterotoxin", "(", "estB", ")", "and", "alkaline", "phosphatase", "(", "phoA", ")", "was", "constructed", ",", "and", "the", "expressed", "protein", "product", "was", "characterized", ".", "The", "STb", "-", "alkaline", "phosphatase", "protein", "(", "STb", "-", "PhoA", ")", "had", "an", "apparent", "molecular", "mass", "of", "50,000", "daltons", "and", "was", "detected", "with", "both", "monoclonal", "anti", "-", "alkaline", "phosphatase", "and", "polyclonal", "anti", "-", "STb", "antibodies", ".", "Expression", "of", "the", "gene", "fusion", "resulted", "in", "high", "-", "level", "production", "of", "alkaline", "phosphatase", "activity", ",", "indicating", "that", "STb", "-", "PhoA", "was", "processed", "and", "exported", "into", "the", "periplasm", "of", "the", "E.", "coli", "host", "strain", ".", "Amino", "acid", "sequence", "analysis", "of", "the", "hybrid", "protein", "yielded", "the", "sequence", "Ser", "-", "Thr", "-", "Gln", "-", "Ser", "-", "Asn", "-", "Lys", "-", "Lys", ",", "indicating", "that", "STb", "-", "PhoA", "was", "processed", "during", "export", "in", "a", "fashion", "identical", "to", "that", "of", "native", "STb", "(", "Y.", "M.", "Kupersztoch", ",", "K.", "Tachias", ",", "C.", "R.", "Moomaw", ",", "L.", "A.", "Dreyfus", ",", "R.", "G.", "Urban", ",", "C.", "Slaughter", ",", "and", "S.", "Whipp", ",", "J.", "Bacteriol", ".", "172", ":", "2427", "-", "2432", ",", "1990", ")", ".", "STb", "-", "PhoA", "was", "purified", "from", "an", "expressed", "bacterial", "lysate", "by", "preparative", "isoelectric", "focusing", ".", "In", "a", "rat", "ligated", "intestinal", "loop", "model", ",", "purified", "STb", "-", "PhoA", "induced", "highly", "significant", "(", "P", "less", "than", "0.002", ")", "fluid", "secretion", ".", "In", "addition", ",", "the", "specific", "activity", "of", "STb", "-", "PhoA", "was", "nearly", "identical", "to", "that", "of", "purified", "STb", ".", "Thus", ",", "the", "STb", "-", "PhoA", "hybrid", "protein", "represents", "a", "readily", "obtainable", "source", "of", "biologically", "active", "(", "STb", ")", "enterotoxin", "that", "may", "prove", "useful", "in", "studies", "to", "determine", "the", "mode", "of", "toxin", "action", "." ]
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27,532
[ "According", "to", "the", "World", "Health", "Organization", ",", "Salmonella", "is", "one", "of", "the", "most", "important", "zoonotic", "foodborne", "pathogens", ".", "Poultry", "products", "are", "thought", "to", "be", "the", "main", "source", "of", "Salmonella", ",", "which", "means", "that", "it", "is", "necessary", "to", "control", "Salmonella", "at", "the", "pre", "-", "harvest", "stage", ".", "Bacteriophages", ",", "acting", "as", "host", "-", "specific", "parasites", "of", "bacterial", "cells", ",", "represent", "one", "of", "the", "alternatives", "to", "antibiotics", "that", "can", "contribute", "to", "food", "safety", "and", "security", ".", "The", "present", "study", "evaluated", "the", "effectiveness", "of", "the", "bacteriophage", "cocktail", "SalmoFREE", "®", "to", "control", "Salmonella", "on", "a", "commercial", "broiler", "farm", ".", "We", "assessed", "the", "relationship", "between", "the", "use", "of", "SalmoFREE", "®", "and", "productivity", "parameters", "(", "feed", "conversion", ",", "weight", "gain", ",", "homogeneity", ")", ".", "Two", "field", "trials", "(", "trial", "1", "n", "=", "34,986", ";", "trial", "2", "n", "=", "34,680", ")", "were", "carried", "out", "under", "commercial", "rearing", "conditions", "on", "a", "Colombian", "broiler", "farm", "with", "a", "record", "of", "Salmonella", "presence", ".", "Each", "trial", "comprised", "2", "control", "chicken", "houses", "and", "2", "experimental", "ones", ".", "SalmoFREE", "®", "and", "a", "control", "suspension", "were", "delivered", "in", "the", "drinking", "water", "at", "3", "time", "points", "in", "the", "production", "cycle", ",", "and", "the", "presence", "of", "Salmonella", "was", "assessed", "in", "cloacal", "swabs", "the", "day", "before", "and", "after", "the", "treatments", ".", "Results", "revealed", "that", "SalmoFREE", "®", "controls", "the", "incidence", "of", "Salmonella", "and", "does", "not", "affect", "the", "animals", "nor", "the", "production", "parameters", ",", "demonstrating", "its", "efficacy", "and", "innocuity", "at", "the", "production", "scale", ".", "We", "detected", "phage", "-", "specific", "genes", "in", "samples", "of", "total", "DNA", "extracted", "from", "ceca", "after", "the", "treatment", "with", "SalmoFREE", "®", ",", "and", "tested", "for", "the", "appearance", "of", "cocktail", "-", "resistant", "Salmonella", ",", "which", "showed", "to", "be", "an", "uncommon", "event", ".", "These", "results", "contribute", "relevant", "information", "to", "the", "adoption", "of", "phage", "therapy", "as", "an", "alternative", "to", "growth", "-", "promoter", "antibiotics", "on", "poultry", "farms", "." ]
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16,394
[ "In", "many", "pathogenic", "bacteria", ",", "genes", "that", "encode", "virulence", "factors", "are", "located", "in", "the", "genomes", "of", "prophages", ".", "Clearly", "bacteriophages", "are", "important", "vectors", "for", "disseminating", "virulence", "genes", ",", "but", ",", "in", "addition", ",", "do", "phage", "regulatory", "circuits", "contribute", "to", "expression", "of", "these", "genes", "?", "Phages", "of", "the", "lambda", "family", "that", "have", "genes", "encoding", "Shiga", "toxin", "are", "found", "in", "certain", "pathogenic", "Escherichia", "coli", "(", "known", "as", "Shiga", "toxin", "producing", "E.", "coli", ")", "and", "the", "filamentous", "phage", "CTXphi", ",", "that", "carries", "genes", "encoding", "cholera", "toxin", "(", "CTX", ")", ",", "is", "found", "in", "Vibrio", "cholerae", ".", "Both", "the", "lambda", "and", "CTXphi", "phages", "have", "repressor", "systems", "that", "maintain", "their", "respective", "prophages", "in", "a", "quiescent", "state", ",", "and", "in", "both", "types", "of", "prophages", "this", "repressed", "state", "is", "abolished", "when", "the", "host", "cell", "SOS", "response", "is", "activated", ".", "In", "the", "lambda", "type", "of", "prophages", ",", "only", "binding", "of", "the", "phage", "-", "encoded", "repressor", "is", "involved", "in", "repression", "and", "this", "repressor", "ultimately", "controls", "Shiga", "toxin", "production", "and/or", "release", ".", "In", "the", "CTXphi", "prophage", ",", "binding", "of", "LexA", ",", "the", "bacterial", "regulator", "of", "SOS", ",", "in", "addition", "to", "binding", "of", "the", "repressor", "is", "involved", "in", "repression", ";", "the", "repressor", "has", "only", "limited", "control", "over", "CTX", "production", "and", "has", "no", "influence", "on", "its", "release", "." ]
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16,354
[ "Elevated", "levels", "of", "B", "-", "cell", "-", "activating", "factor", "of", "the", "TNF", "family", "(", "BAFF", ")", "have", "been", "implicated", "in", "the", "pathogenesis", "of", "autoimmune", "diseases", "in", "human", ".", "We", "now", "report", "the", "isolation", "by", "phage", "display", "of", "human", "single", "-", "chain", "antibody", "fragment", "(", "scFv", ")", "anti", "-", "BAFF", ".", "After", "four", "rounds", "of", "panning", "against", "BAFF", ",", "thirty", "-", "two", "out", "of", "92", "phage", "clones", "displayed", "BAFF", "binding", "activity", ".", "One", "of", "the", "positive", "clones", ",", "designated", "F8", ",", "bound", "to", "BAFF", "with", "relatively", "high", "affinity", "and", "neutralized", "BAFF", "bioactivity", "in", "vitro", ".", "F8", "clone", "was", "expressed", "in", "soluble", "form", "in", "Escherichia", "coli", "HB2151", "and", "purified", "by", "immobilized", "metal", "affinity", "chromatography", "(", "IMAC", ")", ".", "The", "purified", "scFv", "recognized", "BAFF", "with", "the", "affinity", "constant", "(", "K(aff", ")", ")", "of", "2.5", "x", "10(7)M(-1", ")", "without", "cross", "-", "reaction", "to", "APRIL", ".", "In", "addition", "to", "binding", ",", "the", "purified", "scFv", "could", "does", "-", "dependently", "inhibit", "BAFF", "-", "induced", "mouse", "spleen", "B", "lymphocyte", "proliferation", ".", "Together", "with", "its", "fully", "human", "mature", ",", "F8", "scFv", "may", "have", "therapeutic", "implications", "in", "therapy", "of", "autoimmune", "disorders", "mediated", "by", "BAFF", "." ]
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20,906
[ "Bacteria", "are", "constantly", "threatened", "by", "predation", "from", "bacteriophage", "parasites", "and", ",", "in", "response", ",", "have", "evolved", "an", "array", "of", "resistance", "mechanisms", ".", "These", "resistance", "mechanisms", "then", "place", "greater", "selection", "pressure", "on", "the", "infecting", "bacteriophages", ",", "which", "develop", "counter", "-", "strategies", "in", "a", "perpetual", "'", "arms", "race", "'", "between", "virus", "and", "host", ".", "Toxin", "-", "antitoxin", "(", "TA", ")", "loci", "are", "widespread", "in", "bacteria", "and", "can", "confer", "multiple", "benefits", ",", "including", "resistance", "to", "bacteriophages", ".", "The", "study", "by", "Otsuka", "and", "Yonesaki", ",", "published", "in", "this", "issue", "of", "Molecular", "Microbiology", ",", "describes", "a", "new", "plasmid", "-", "encoded", "TA", "system", ",", "lsoAB", ",", "which", "confers", "resistance", "to", "a", "dmd(-", ")", "mutant", "of", "bacteriophage", "T4", "through", "the", "activity", "of", "the", "LsoA", "toxin", ".", "Infections", "with", "wild", "-", "type", "T4", ",", "however", ",", "are", "unaffected", "as", "the", "Dmd", "protein", "acts", "as", "an", "alternative", "antitoxin", "to", "LsoA", ",", "thus", "preventing", "its", "anti", "-", "bacteriophage", "activity", ".", "Dmd", "has", "also", "been", "shown", "to", "negate", "the", "activity", "of", "a", "related", "toxin", ",", "RnlA.", "This", "is", "a", "striking", "result", "indicating", "that", "Dmd", "can", "act", "as", "a", "promiscuous", "antitoxin", ",", "binding", "and", "inhibiting", "multiple", "toxin", "partners", ",", "when", "antitoxin", "activity", "is", "generally", "considered", "to", "be", "limited", "to", "a", "single", "cognate", "toxin", ".", "This", "study", "is", "an", "exciting", "addition", "to", "both", "the", "bacteriophage", "resistance", "and", "TA", "fields", ",", "and", "suggests", "a", "greater", "role", "for", "TA", "system", "-", "based", "resistance", "and", "counter", "-", "resistance", "in", "the", "world", "'s", "oldest", "predator", "-", "prey", "relationship", "." ]
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29,677
[ "Despite", "enhanced", "sanitation", "implementations", ",", "foodborne", "bacterial", "pathogens", "still", "remain", "a", "major", "threat", "to", "public", "health", "and", "generate", "high", "costs", "for", "the", "food", "industry", ".", "Reporter", "bacteriophage", "(", "phage", ")", "systems", "have", "been", "regarded", "as", "a", "powerful", "technology", "for", "diagnostic", "assays", "for", "their", "extraordinary", "specificity", "to", "target", "cells", "and", "cost", "-", "effectiveness", ".", "Our", "study", "introduced", "an", "enzyme", "-", "based", "fluorescent", "assay", "for", "detecting", "the", "presence", "of", "E.", "coli", "using", "the", "T7", "phage", "engineered", "with", "the", "lacZ", "operon", "which", "encodes", "beta", "-", "galactosidase", "(", "β", "-", "gal", ")", ".", "Both", "endogenous", "and", "overexpressed", "β", "-", "gal", "expression", "was", "monitored", "using", "a", "fluorescent", "-", "based", "method", "with", "4", "-", "methylumbelliferyl", "β", "-", "d", "-", "galactopyranoside", "(", "MUG", ")", "as", "the", "substrate", ".", "The", "infection", "of", "E.", "coli", "with", "engineered", "phages", "resulted", "in", "a", "detection", "limit", "of", "10", "CFU", "/", "mL", "in", "ground", "beef", "juice", "after", "7", "h", "of", "incubation", ".", "In", "this", "study", ",", "we", "demonstrated", "that", "the", "overexpression", "of", "β", "-", "gal", "coupled", "with", "a", "fluorogenic", "substrate", "can", "provide", "a", "straightforward", "and", "sensitive", "approach", "to", "detect", "the", "potential", "biological", "contamination", "in", "food", "samples", ".", "The", "results", "also", "suggested", "that", "this", "system", "can", "be", "applied", "to", "detect", "E.", "coli", "strains", "isolated", "from", "environmental", "samples", ",", "indicating", "a", "broader", "range", "of", "bacterial", "detection", "." ]
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13,530
[ "This", "study", "describes", "the", "identification", "of", "the", "epitope", "recognized", "by", "the", "tobacco", "mosaic", "virus", "(", "TMV", ")", "coat", "protein", "(", "CP)-specific", "monoclonal", "antibody", "29", "(", "MAb29", ")", "by", "displaying", "a", "CP", "gene", "-", "fragment", "library", "on", "pVIII", "of", "filamentous", "phage", "M13", ".", "More", "than", "80", "%", "of", "the", "clones", "isolated", "after", "one", "round", "of", "panning", "bound", "specifically", "to", "MAb29", ".", "DNA", "sequencing", "of", "ten", "randomly", "chosen", "MAb29", "-", "specific", "clones", "and", "subsequent", "sequence", "comparison", "revealed", "a", "common", "seven", "amino", "acid", "epitope", "(", "ELIRGTG", ")", "representing", "amino", "acids", "131", "-", "137", "of", "the", "TMV", "CP", ".", "The", "reactivity", "of", "MAb29", "in", "competition", "ELISA", "towards", "glutathione", "S:-transferase", "fused", "to", "this", "epitope", "was", "stronger", "than", "that", "towards", "full", "-", "length", "wild", "-", "type", "TMV", "CP", ",", "confirming", "the", "epitope", "sequence", "determined", "by", "gene", "-", "fragment", "phage", "display", ".", "This", "demonstrated", "that", "gene", "-", "fragment", "libraries", "displayed", "on", "the", "phage", "surface", "as", "fusion", "proteins", "with", "the", "filamentous", "bacteriophage", "gene", "VIII", "are", "useful", "tools", "for", "rapid", "identification", "of", "linear", "epitopes", "recognized", "by", "MAbs", "." ]
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27,883
[ "Antibiotics", "have", "saved", "millions", "of", "lives", ".", "However", ",", "the", "overuse", "and", "misuse", "of", "antibiotics", "have", "contributed", "to", "a", "rapid", "emergence", "of", "antibiotic", "resistance", "worldwide", ".", "In", "addition", ",", "there", "is", "an", "unprecedented", "void", "in", "the", "development", "of", "new", "antibiotic", "classes", "by", "the", "pharmaceutical", "industry", "since", "the", "first", "introduction", "of", "antibiotics", ".", "This", "antibiotic", "crisis", "underscores", "the", "urgent", "and", "increasing", "necessity", "of", "new", ",", "innovative", "antibiotics", ".", "Enzybiotics", "are", "such", "a", "promising", "class", "of", "antibiotics", ".", "They", "are", "derived", "from", "endolysins", ",", "bacteriophage", "-", "encoded", "enzymes", "that", "degrade", "the", "bacterial", "cell", "wall", "of", "the", "infected", "cell", "at", "the", "end", "of", "the", "lytic", "replication", "cycle", ".", "Enzybiotics", "are", "featured", "by", "a", "rapid", "and", "unique", "mode", "-", "of", "-", "action", ",", "a", "high", "specificity", "to", "kill", "pathogens", ",", "a", "low", "probability", "for", "bacterial", "resistance", "development", "and", "a", "proteinaceous", "nature", ".", "(", "Engineered", ")", "endolysins", "have", "been", "demonstrated", "to", "be", "effective", "in", "a", "variety", "of", "animal", "models", "to", "combat", "both", "Gram", "-", "positive", "and", "Gram", "-", "negative", "bacteria", "and", "have", "entered", "different", "phases", "of", "preclinical", "and", "clinical", "trials", ".", "In", "addition", ",", "mycobacteriophage", "-", "encoded", "endolysins", "have", "been", "successfully", "used", "to", "inhibit", "mycobacteria", "in", "vitro", ".", "In", "this", "chapter", "we", "focus", "on", "the", "(", "pre)clinical", "progress", "of", "enzybiotics", "as", "potent", "therapeutic", "agent", "against", "human", "pathogenic", "bacteria", "." ]
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19,354
[ "A", "method", "was", "developed", "for", "oriented", "immobilization", "of", "bacteriophage", "T4", "through", "introduction", "of", "specific", "binding", "ligands", "into", "the", "phage", "head", "using", "a", "phage", "display", "technique", ".", "Fusion", "of", "the", "biotin", "carboxyl", "carrier", "protein", "gene", "(", "bccp", ")", "or", "the", "cellulose", "binding", "module", "gene", "(", "cbm", ")", "with", "the", "small", "outer", "capsid", "protein", "gene", "(", "soc", ")", "of", "T4", "resulted", "in", "expression", "of", "the", "respective", "ligand", "on", "the", "phage", "head", ".", "Recombinant", "bacteriophages", "were", "characterized", "in", "terms", "of", "infectivity", ".", "It", "was", "shown", "that", "both", "recombinant", "phages", "retain", "their", "lytic", "activity", "and", "host", "range", ".", "However", ",", "phage", "head", "modification", "resulted", "in", "a", "decreased", "burst", "size", "and", "an", "increased", "latent", "period", ".", "The", "efficiency", "of", "bacteriophage", "immobilization", "with", "streptavidin", "-", "coated", "magnetic", "beads", "and", "cellulose", "-", "based", "materials", "was", "investigated", ".", "It", "was", "shown", "that", "recombinant", "bacteriophages", "form", "specific", "and", "strong", "bonds", "with", "their", "respective", "solid", "support", "and", "are", "able", "to", "specifically", "capture", "and", "infect", "the", "host", "bacterium", ".", "Thus", ",", "the", "use", "of", "immobilized", "BCCP", "-", "T4", "bacteriophage", "for", "an", "Escherichia", "coli", "B", "assay", "using", "a", "phage", "multiplication", "approach", "and", "real", "-", "time", "PCR", "allowed", "detection", "of", "as", "few", "as", "800", "cells", "within", "2", "h." ]
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13,557
[ "OBJECTIVE", ":", "To", "perform", "a", "comparative", "analysis", "of", "1", ")", "intravenous", "Ig", "(", "IVIG)-bound", "Fab", "fragments", "from", "a", "patient", "with", "autoimmune", "thrombocytopenia", "that", "had", "progressed", "to", "systemic", "lupus", "erythematosus", "(", "SLE", ")", "and", "2", ")", "IVIG", "-", "selected", "Fabs", "from", "an", "SLE", "patient", "without", "thrombocytopenia", ".", "METHODS", ":", "IVIG", "preparations", "have", "been", "successfully", "used", "to", "treat", "certain", "cases", "of", "autoimmune", "thrombocytopenia", "and", "SLE", ".", "Specific", "interactions", "of", "IVIG", "with", "the", "components", "of", "the", "immune", "system", "are", "not", "well", "characterized", ".", "To", "investigate", "these", ",", "we", "had", "previously", "cloned", "a", "large", "number", "of", "phage", "-", "displayed", "IgG", "Fab", "fragments", ",", "derived", "from", "3", "patients", "with", "autoimmune", "thrombocytopenia", ",", "that", "were", "specifically", "bound", "by", "IVIG", "molecules", "during", "panning", ".", "Many", "of", "these", "Fabs", "reacted", "with", "platelets", ".", "Sequencing", "revealed", "that", "the", "most", "frequently", "used", "VH", "germline", "gene", "segments", "of", "all", "IVIG", "-", "bound", "Fabs", "were", "3", "-", "23", "and", "3", "-", "30/3", "-", "30.5", ".", "One", "patient", "'s", "autoimmune", "thrombocytopenia", "had", "progressed", "to", "SLE", ".", "Using", "the", "same", "cloning", "and", "panning", "procedures", ",", "we", "performed", "a", "comparative", "analysis", "of", "this", "patient", "'s", "IVIG", "-", "bound", "Fab", "fragments", "and", "the", "IVIG", "-", "selected", "Fabs", "from", "an", "SLE", "patient", "without", "thrombocytopenia", ".", "RESULTS", ":", "We", "observed", "an", "exclusive", "selection", "of", "antibodies", "derived", "from", "3", "-", "23", "and", "3", "-", "30/3", "-", "30.5", "germline", "segments", ".", "In", "contrast", "to", "the", "Fab", "fragments", "from", "the", "autoimmune", "thrombocytopenia", "patient", "who", "developed", "SLE", ",", "none", "of", "the", "IVIG", "-", "selected", "Fabs", "from", "the", "SLE", "patient", "without", "thrombocytopenia", "bound", "to", "thrombocytes", ".", "CONCLUSION", ":", "Our", "results", "suggest", "a", "preferential", "interaction", "of", "a", "subfraction", "of", "IVIG", "-", "representative", "of", "normal", "Ig", "repertoires", "-", "with", "antibodies", "and", "B", "cell", "receptors", "derived", "from", "these", "2", "gene", "segments", ".", "Importantly", ",", "these", "are", "the", "most", "frequently", "rearranged", "VH", "germline", "genes", "among", "human", "B", "cells", ".", "This", "kind", "of", "interaction", "is", "characteristic", "of", "a", "B", "cell", "superantigen", ",", "since", "light", "chains", ",", "antigen", "specificity", ",", "and", "the", "high", "variation", "in", "the", "third", "complementarity", "-", "determining", "region", "3", "showed", "little", "influence", "on", "the", "selection", "of", "3", "-", "23-", "or", "3", "-", "30/3", "-", "30.5", "-", "derived", "Fabs", "by", "IVIG", ".", "However", ",", "at", "least", "some", "of", "the", "contact", "residues", "on", "Fabs", "for", "IVIG", "appear", "to", "be", "different", "from", "those", "for", "staphylococcal", "protein", "A", "and", "human", "immunodeficiency", "virus", "gp", "120", ".", "The", "IVIG", "-", "selected", "Fabs", "may", "now", "be", "used", "to", "clone", "antibodies", "representative", "of", "this", "IVIG", "subfraction", "to", "study", "their", "possible", "regulatory", "influence", "on", "the", "B", "cell", "repertoire", "during", "normal", "development", "and", "disease", "." ]
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7,544
[ "The", "radiation", "chemistry", "of", "nucleotide", "damage", "introduction", "into", "DNA", "gamma", "-", "irradiated", "in", "dilute", "aqueous", "solution", "has", "been", "studied", "with", "a", "damage", "-", "specific", "DNA", "binding", "protein", ".", "Irradiation", "in", "air", ",", "N2", "or", "N2O", "in", "the", "presence", "and", "absence", "of", "free", "radical", "scavengers", "revealed", "that", "protein", "-", "recognizable", "lesions", "were", "introduced", "both", "by", "the", "hydrated", "electron", "and", "by", "the", "combination", "of", "the", "hydroxyl", "radical", "and", "superoxide", "anion", "radical", ",", "but", "not", "by", "the", "hydroxyl", "radical", "alone", ".", "In", "addition", ",", "nucleotide", "damage", "was", "introduced", "into", "DNA", "by", "an", "enzymatic", "superoxide", "-", "generating", "system", "." ]
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30,142
[ "Infections", "related", "to", "antibiotic", "resistant", "bacteria", "are", "accelerating", "on", "a", "global", "scale", ",", "and", "hence", "to", "encounter", "this", "problem", "in", "case", "of", "urinary", "tract", "infections", ";", "bacteriophages", "were", "isolated", "for", "biocontrol", "of", "multi", "-", "drug", "resistant", "(", "MDR", ")", "uropathogenic", "Escherichia", "coli", "(", "UPECs", ")", "isolates", ".", "Four", "lytic", "phages", "were", "purified", ",", "characterized", ",", "and", "evaluated", "for", "their", "effectiveness", "in", "the", "form", "of", "cocktail", "and", "in", "synergy", "with", "antibiotics", ".", "Morphological", "features", "and", "other", "life", "cycle", "specifications", "of", "phages", "revealed", "that", "two", "phages", "Escherichia", "phage", "FS11", "and", "Escherichia", "phage", "FS17", "belonged", "to", "Myoviridae", "and", "the", "other", "two", "phages", "Escherichia", "phage", "PS8", "and", "Escherichia", "phage", "PS6", "belonged", "to", "Siphoviridae", "family", "of", "order", "Caudovirales", ".", "One", "step", "growth", "curve", "analysis", "demonstrated", "that", "phage", "FS11", "and", "phage", "FS17", "had", "latent", "time", "of", "24", "min", "and", "26", "min", ",", "and", "a", "burst", "size", "of", "~121", "and", "98", "phage", "particles/", "cell", "respectively", ";", "while", "for", "phage", "PS8", "and", "phage", "PS6", ",", "the", "latent", "time", "was", "42", "min", "and", "35", "min", ",", "and", "the", "burst", "size", "was", "87", "and", "78", "particles/", "cell", ",", "respectively", ";", "depicting", "the", "lytic", "nature", "of", "phages", ".", "The", "use", "of", "all", "four", "phages", "together", "in", "the", "form", "of", "a", "cocktail", "resulted", "into", "a", "considerable", "enhancement", "in", "the", "lytic", "ability", ";", "the", "phage", "cocktail", "lysed", "86.7", "%", "of", "the", "clinical", "isolates", ",", "compared", "to", "lysis", "in", "the", "range", "of", "50%-66", "%", "by", "individual", "phages", ".", "Studies", "on", "in", "vitro", "evaluation", "of", "phage", "-", "antibiotic", "combinations", "revealed", "synergism", "between", "antibiotics", "and", "the", "phage", "cocktail", "(", "phage", "PS6", "and", "phage", "FS17", ")", ",", "wherein", "the", "phage", "cocktail", "was", "observed", "to", "efficiently", "inhibit", "the", "strains", "in", "the", "presence", "of", "sub", "-", "lethal", "doses", "of", "antibiotics", ".", "The", "study", "thus", "concludes", "that", "the", "use", "of", "multiple", "phages", "and", "phage", "-", "antibiotic", "combinations", "could", "prove", "beneficial", "in", "the", "era", "of", "rapidly", "increasing", "drug", "-", "resistant", "strains", "." ]
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14,235
[ "A", "striking", "common", "feature", "in", "the", "maturation", "of", "all", "linear", "double", "-", "stranded", "DNA", "viruses", "is", "that", "their", "lengthy", "genome", "is", "translocated", "with", "remarkable", "velocity", "into", "the", "limited", "space", "within", "a", "preformed", "protein", "shell", "and", "packaged", "into", "near", "crystalline", "density", ".", "A", "DNA", "-", "translocating", "motor", ",", "powered", "by", "ATP", "hydrolysis", ",", "accomplishes", "this", "task", ",", "which", "would", "otherwise", "be", "energetically", "unfavorable", ".", "DNA", "-", "packaging", "RNA", ",", "pRNA", ",", "forms", "a", "hexameric", "complex", "to", "serve", "as", "a", "vital", "component", "of", "the", "DNA", "translocating", "motor", "of", "bacterial", "virus", "Phi29", ".", "The", "sequential", "action", "of", "six", "pRNA", "ensures", "continual", "function", "in", "the", "DNA", "translocation", "process", ".", "The", "Phi29", "motor", "has", "been", "assembled", "with", "purified", "components", "synthesized", "by", "chemical", "or", "biotechnological", "approaches", "and", "is", "able", "to", "pump", "the", "viral", "DNA", "into", "the", "protein", "shell", "in", "vitro", ".", "pRNA", "dimers", "are", "the", "building", "blocks", "of", "the", "hexamer", ".", "The", "computer", "models", "of", "the", "three", "-", "dimensional", "structure", "of", "the", "motor", "was", "constructed", "based", "on", "experimental", "data", "derived", "from", "photoaffinity", "cross", "-", "linking", "by", "psoralen", ",", "phenphi", "(", "cis", "-", "Rh(1,10", "-", "phenanthroline)(9,10", "-", "phenan", "-", "threnequinone", "diimine)Cl(2)(+", ")", ")", ",", "and", "azidophenacyl", ";", "chemical", "modification", "and", "chemical", "modification", "interference", "with", "dimethyl", "sulfate", ",", "1", "-", "cyclohexyl-3-(2", "-", "morpholinoethyl)carbodiimide", "metho", "-", "p", "-", "toluene", "sulfonate", ",", "and", "kethoxal", ";", "complementary", "modification", ";", "and", "nuclease", "probing", "by", "single-", "and", "double", "-", "stranded", "specific", "RNases", ".", "The", "shapes", "of", "these", "computer", "models", "are", "very", "similar", "to", "the", "published", "pRNA", "images", "of", "cryo", "-", "atomic", "force", "microscopy", ".", "pRNA", "hexamer", "docking", "with", "the", "connector", "crystal", "structure", "reveals", "a", "very", "impressive", "match", "with", "the", "available", "biochemical", ",", "genetic", ",", "and", "physical", "data", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
25,618
[ "Clustered", ",", "regularly", "interspaced", ",", "short", ",", "palindromic", "repeats", "(", "CRISPR", ")", "loci", ",", "together", "with", "their", "CRISPR", "-", "associated", "(", "Cas", ")", "proteins", ",", "provide", "bacteria", "and", "archaea", "with", "adaptive", "immunity", "against", "invasion", "by", "bacteriophages", ",", "plasmids", ",", "and", "other", "mobile", "genetic", "elements", ".", "These", "host", "defenses", "impart", "selective", "pressure", "on", "phages", "and", "mobile", "elements", "to", "evolve", "countermeasures", "against", "CRISPR", "immunity", ".", "As", "a", "consequence", "of", "this", "pressure", ",", "phages", "and", "mobile", "elements", "have", "evolved", "'", "anti", "-", "CRISPR", "'", "proteins", "that", "function", "as", "direct", "inhibitors", "of", "diverse", "CRISPR", "-", "Cas", "effector", "complexes", ".", "Some", "of", "these", "CRISPR", "-", "Cas", "complexes", "can", "be", "deployed", "as", "genome", "engineering", "platforms", ",", "and", "anti", "-", "CRISPRs", "could", "therefore", "be", "useful", "in", "exerting", "spatial", ",", "temporal", ",", "or", "conditional", "control", "over", "genome", "editing", "and", "related", "applications", ".", "Here", "we", "describe", "the", "discovery", "of", "anti", "-", "CRISPRs", ",", "the", "range", "of", "CRISPR", "-", "Cas", "systems", "that", "they", "inhibit", ",", "their", "mechanisms", "of", "action", ",", "and", "their", "potential", "utility", "in", "biotechnology", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
11,489
[ "Seven", "random", "peptide", "libraries", "(", "two", "displaying", "linear", "peptides", "and", "five", "displaying", "cysteine", "-", "constrained", "peptides", ")", "were", "constructed", "as", "gene", "III", "fusion", "proteins", "of", "the", "bacteriophage", "fd", "-", "tet", ".", "These", "libraries", "were", "used", "to", "screen", "a", "blocking", "monoclonal", "antibody", "raised", "against", "B7", "-", "1", "(", "CD80", ")", ",", "a", "human", "cell", "surface", "antigen", "that", "binds", "two", "T", "cell", "receptors", ",", "CD28", "and", "CTLA-4", ".", "After", "three", "rounds", "of", "screening", "against", "the", "immobilized", "antibody", ",", "1000", "-", "fold", "enrichment", "was", "observed", "in", "libraries", "displaying", "both", "linear", "and", "cysteine", "-", "constrained", "peptides", ".", "DNA", "sequencing", "of", "the", "enriched", "phage", "revealed", "two", "distinct", "consensus", "sequences", ":", "HXG(A", "/", "Y)XH", "and", "DVCXXGGPGC", ".", "Phage", "expressing", "these", "consensus", "sequences", "bound", "to", "L307.4", "but", "not", "to", "an", "isotype", "matched", "antibody", ",", "indicating", "that", "binding", "was", "antibody", "specific", ".", "Synthetic", "peptides", "corresponding", "to", "both", "motifs", "inhibited", "phage", "binding", "to", "L307.4", ",", "indicating", "that", "the", "gene", "III", "protein", "is", "not", "required", "for", "peptide", "binding", ".", "In", "addition", ",", "the", "cyclized", "forms", "of", "synthetic", "peptides", "containing", "the", "DVCXXGGPGC", "motif", "were", "capable", "of", "inhibiting", "L307.4", "binding", "to", "soluble", "B7", "-", "1", "/", "Fc", "fusion", ".", "Moreover", ",", "phage", "expressing", "only", "the", "HXG(A", "/", "Y)XH", "consensus", "sequence", "were", "inhibited", "from", "binding", "to", "L307.4", "by", "the", "presence", "of", "chelating", "agents", ".", "These", "results", "indicate", "that", "the", "framework", "within", "which", "the", "peptide", "is", "presented", "on", "the", "surface", "of", "the", "phage", "may", "allow", "the", "identification", "of", "unique", "peptide", "motifs", "with", "distinct", "binding", "characteristics", ".", "These", "peptide", "motifs", "could", "be", "used", "for", "the", "design", "of", "peptidomimetics", "with", "therapeutic", "applications", "if", "they", "inhibit", "the", "binding", "of", "B7", "-", "1", "to", "its", "T", "cell", "receptors", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
31,704
[ "Phages", "and", "prophages", "are", "one", "of", "the", "principal", "modulators", "of", "microbial", "populations", ".", "However", ",", "much", "of", "their", "diversity", "is", "still", "poorly", "understood", ".", "Here", ",", "we", "extracted", "33,624", "prophages", "from", "13,713", "complete", "prokaryotic", "genomes", "to", "explore", "the", "prophage", "diversity", "and", "their", "relationships", "with", "their", "host", ".", "Our", "results", "reveal", "that", "prophages", "were", "present", "in", "75", "%", "of", "the", "genomes", "studied", ".", "In", "addition", ",", "Enterobacterales", "were", "significantly", "enriched", "in", "prophages", ".", "We", "also", "found", "that", "pathogens", "are", "a", "significant", "reservoir", "of", "prophages", ".", "Finally", ",", "we", "determined", "that", "the", "prophage", "relatedness", "and", "the", "range", "of", "genomic", "hosts", "were", "delimited", "by", "the", "evolutionary", "relationships", "of", "their", "hosts", ".", "On", "a", "broader", "level", ",", "we", "got", "insights", "into", "the", "prophage", "population", ",", "identified", "in", "thousands", "of", "publicly", "available", "prokaryotic", "genomes", ",", "by", "comparing", "the", "prophage", "distribution", "and", "relatedness", "between", "them", "and", "their", "hosts", ".", "IMPORTANCE", "Phages", "and", "prophages", "play", "an", "essential", "role", "in", "controlling", "their", "host", "populations", "either", "by", "modulating", "the", "host", "abundance", "or", "providing", "them", "with", "genes", "that", "benefit", "the", "host", ".", "The", "constant", "growth", "in", "next", "-", "generation", "sequencing", "technology", "has", "caused", "the", "development", "of", "powerful", "computational", "tools", "to", "identify", "phages", "and", "prophages", "with", "high", "precision", ".", "Making", "it", "possible", "to", "explore", "the", "prophage", "populations", "integrated", "into", "host", "genomes", "on", "a", "large", "scale", ".", "However", ",", "it", "is", "still", "a", "new", "and", "under", "-", "explored", "area", ",", "and", "efforts", "are", "still", "required", "to", "identify", "prophage", "populations", "to", "understand", "their", "dynamics", "with", "their", "hosts", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
20,749
[ "Ralstonia", "solanacearum", "is", "the", "causative", "agent", "of", "bacterial", "wilt", "in", "many", "important", "crops", ".", "ϕRSS1", "is", "a", "filamentous", "phage", "that", "infects", "R.", "solanacearum", "strains", ".", "Upon", "infection", ",", "it", "alters", "the", "physiological", "state", "and", "the", "behavior", "of", "host", "cells", ".", "Here", ",", "we", "show", "that", "R.", "solanacearum", "infected", "by", "ϕRSS1", "becomes", "more", "virulent", "on", "host", "plants", ".", "Some", "virulence", "and", "pathogenicity", "factors", ",", "such", "as", "extracellular", "polysaccharide", "(", "EPS", ")", "synthesis", "and", "twitching", "motility", ",", "increased", "in", "the", "bacterial", "host", "cells", "infected", "with", "ϕRSS1", ",", "resulting", "in", "early", "wilting", ".", "Tomato", "plants", "inoculated", "with", "ϕRSS1", "-", "infected", "bacteria", "wilted", "2", "to", "3", "days", "earlier", "than", "those", "inoculated", "with", "wild", "-", "type", "bacteria", ".", "Infection", "with", "ϕRSS1", "induced", "early", "expression", "of", "phcA", ",", "the", "global", "virulence", "regulator", ".", "phcA", "expression", "was", "detected", "in", "ϕRSS1", "-", "infected", "cells", "at", "cell", "density", "as", "low", "as", "10(4", ")", "CFU", "/", "ml", ".", "Filamentous", "phages", "are", "assembled", "on", "the", "host", "cell", "surface", "and", "many", "phage", "particles", "accumulate", "on", "the", "cell", "surface", ".", "These", "surface", "-", "associated", "phage", "particles", "(", "phage", "proteins", ")", "may", "change", "the", "cell", "surface", "nature", "(", "hydrophobicity", ")", "to", "give", "high", "local", "cell", "densities", ".", "ϕRSS1", "infection", "also", "enhanced", "PilA", "and", "type", "IV", "pilin", "production", ",", "resulting", "in", "increased", "twitching", "motility", "." ]
[ 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
759
[ "An", "endonuclease", "having", "EcoRI", "specificity", "is", "produced", "by", "bacteria", "containing", "the", "ColE1", "plasmid", ".", "Such", "bacterial", "cells", "fail", "to", "express", "restriction", "or", "modification", "functions", "in", "vivo", ",", "and", "phage", "or", "plasmid", "DNA", "obtained", "from", "ColE1", "-", "containing", "cells", "has", "unmodified", "EcoRI", "sites", "that", "are", "cleaved", "in", "vitro", "by", "purified", "EcoRI", "endonuclease", "or", "by", "enzyme", "extracted", "from", "bacteria", "that", "carry", "ColE1", ".", "No", "EcoRI", "DNA", "methylase", "activity", "associated", "with", "ColE1", "has", "been", "detected", ".", "The", "finding", "of", "phenotypically", "cryptic", "ColE1", "-", "dependent", "EcoRI", "endonuclease", "activity", "and", "the", "absence", "of", "any", "detectable", "EcoRI", "modification", "system", "in", "ColE1", "-", "containing", "cells", "suggest", "a", "control", "mechanism", "that", "appears", "to", "prevent", "functional", "expression", "of", "the", "ColE1", "-", "determined", "enzyme", "in", "vivo", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
29,991
[ "The", "common", "cooccurrence", "of", "antibiotics", "and", "phages", "in", "both", "natural", "and", "engineered", "environments", "underscores", "the", "need", "to", "understand", "their", "interactions", "and", "implications", "for", "bacterial", "control", "and", "antibiotic", "resistance", "propagation", ".", "Here", ",", "aminoglycoside", "antibiotics", "that", "inhibit", "protein", "synthesis", "(", "e.g.", ",", "kanamycin", "and", "neomycin", ")", "impeded", "the", "replication", "of", "coliphage", "T3", "and", "Bacillus", "phage", "BSP", ",", "reducing", "their", "infection", "efficiency", "and", "mitigating", "their", "hindrance", "of", "bacterial", "growth", ",", "biofilm", "formation", ",", "and", "tolerance", "to", "antibiotics", ".", "For", "example", ",", "treatment", "with", "phage", "T3", "reduced", "subsequent", "biofilm", "formation", "by", "Escherichia", "coli", "liquid", "cultures", "to", "53", "%", "±", "5", "%", "of", "that", "of", "the", "no", "-", "phage", "control", ",", "but", "a", "smaller", "reduction", "of", "biofilm", "formation", "(", "89", "%", "±", "10", "%", ")", "was", "observed", "for", "combined", "exposure", "to", "phage", "T3", "and", "kanamycin", ".", "Despite", "sharing", "a", "similar", "mode", "of", "action", "with", "aminoglycosides", "(", "i.e.", ",", "inhibiting", "protein", "synthesis", ")", "and", "antagonizing", "phage", "replication", ",", "albeit", "to", "a", "lesser", "degree", ",", "tetracyclines", "did", "not", "inhibit", "bacterial", "control", "by", "phages", ".", "Phage", "T3", "combined", "with", "tetracycline", "showed", "higher", "suppression", "of", "biofilm", "formation", "than", "when", "combined", "with", "aminoglycosides", "(", "25", "%", "±", "6", "%", "of", "the", "no", "-", "phage", "control", ")", ".", "The", "addition", "of", "phage", "T3", "to", "E.", "coli", "suspensions", "with", "tetracycline", "also", "suppressed", "the", "development", "of", "tolerance", "to", "tetracycline", ".", "However", ",", "this", "suppression", "of", "antibiotic", "tolerance", "development", "disappeared", "when", "tetracycline", "was", "replaced", "with", "3", "mg", "/", "liter", "kanamycin", ",", "corroborating", "the", "greater", "antagonism", "with", "aminoglycosides", ".", "Overall", ",", "this", "study", "highlights", "this", "overlooked", "antagonistic", "effect", "on", "phage", "proliferation", ",", "which", "may", "attenuate", "phage", "suppression", "of", "bacterial", "growth", ",", "biofilm", "formation", ",", "antibiotic", "tolerance", ",", "and", "maintenance", "of", "antibiotic", "resistance", "genes", ".", "IMPORTANCE", "The", "coexistence", "of", "residual", "antibiotics", "and", "phages", "is", "common", "in", "many", "environments", ",", "which", "underscores", "the", "need", "to", "understand", "their", "interactive", "effects", "on", "bacteria", "and", "the", "implications", "for", "antibiotic", "resistance", "propagation", ".", "Here", ",", "aminoglycosides", "acting", "as", "bacterial", "protein", "synthesis", "inhibitors", "impeded", "the", "replication", "of", "various", "phages", ".", "This", "alleviated", "the", "suppressive", "effects", "of", "phages", "against", "bacterial", "growth", "and", "biofilm", "formation", "and", "diminished", "bacterial", "fitness", "costs", "that", "suppress", "the", "emergence", "of", "tolerance", "to", "antibiotics", ".", "We", "show", "that", "changes", "in", "bacteria", "caused", "by", "environmentally", "relevant", "concentrations", "of", "sublethal", "antibiotics", "can", "affect", "phage", "-", "host", "dynamics", "that", "are", "commonly", "overlooked", "in", "vitro", "but", "can", "result", "in", "unexpected", "environmental", "consequences", "." ]
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2,862
[ "Of", "the", "15,170", "cases", "of", "bacteremia", "due", "to", "Staphylococcus", "aureus", "that", "occurred", "in", "Denmark", "between", "1959", "and", "1988", ",", "we", "review", "525", "cases", "of", "acute", "hematogenous", "osteomyelitis", "and", "185", "cases", "of", "septic", "arthritis", "that", "developed", "subsequent", "to", "the", "bacteremia", "and", "134", "cases", "of", "contiguous", "osteomyelitis", "in", "which", "the", "bacteremia", "developed", "secondarily", ".", "The", "pattern", "of", "acute", "infections", "of", "bones", "and", "joints", "has", "changed", "over", "the", "three", "decades", "studied", ".", "The", "frequency", "of", "secondary", "bone", "or", "joint", "infections", "due", "to", "S.", "aureus", "bacteremia", "has", "changed", ",", "as", "have", "the", "phage", "-", "type", "pattern", "and", "antibiotic", "resistance", "of", "the", "infective", "strains", ".", "The", "prevalence", "of", "hospital", "-", "acquired", "cases", "has", "increased", "and", "the", "age", "distribution", "of", "patients", "has", "changed", ",", "as", "is", "reflected", "in", "an", "increasing", "number", "of", "older", "patients", ".", "The", "localization", "of", "hematogenous", "osteomyelitis", "has", "shifted", ",", "and", "the", "vertebral", "column", "is", "now", "the", "most", "common", "site", "of", "infection", ".", "The", "rate", "of", "chronic", "cases", "of", "osteomyelitis", "that", "occur", "following", "acute", "hematogenous", "osteomyelitis", "has", "been", "reduced", "from", "34", "%", "to", "6", "%", ".", "The", "mortality", "associated", "with", "S.", "aureus", "bacteremic", "infections", "of", "bones", "or", "joints", "is", "low", "compared", "to", "that", "associated", "with", "other", "cases", "of", "S.", "aureus", "bacteremia", "." ]
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10,164
[ "A", "culture", "taken", "from", "a", "nursing", "home", "resident", "as", "part", "of", "a", "S.", "enteritidis", "outbreak", "was", "found", "to", "have", "a", "mixed", "infection", "due", "to", "three", "different", "strains", "of", "S.", "enteritidis", ".", "One", "of", "the", "three", "strains", "belonged", "to", "phage", "type", "(", "PT", ")", "4", ",", "one", "to", "PT6", "and", "one", "reacted", "with", "phages", "but", "did", "not", "conform", "to", "any", "typing", "scheme", "(", "RDNC", ")", ".", "All", "three", "strains", "had", "the", "38.9", "megadaltons", "(", "MDa", ")", "plasmid", "found", "in", "the", "isolates", "from", "the", "outbreak", "-", "related", "cases", ",", "in", "addition", "the", "PT6", "and", "RDNC", "strains", "harboured", "a", "69.9", "MDa", "plasmid", ".", "The", "importance", "of", "phage", "typing", "and", "plasmid", "analysis", "for", "S.", "enteritidis", "strain", "characterization", "and", "their", "epidemiologic", "and", "bacterial", "significance", "are", "discussed", "." ]
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26,987
[ "Soft", "-", "rot", "Enterobacteriaceae", "(", "SRE", ")", ",", "typified", "by", "Pectobacterium", "and", "Dickeya", "genera", ",", "are", "phytopathogenic", "bacteria", "inflicting", "soft", "-", "rot", "disease", "in", "crops", "worldwide", ".", "By", "combining", "genomic", "information", "from", "100", "SRE", "with", "whole", "-", "transcriptome", "data", "sets", ",", "we", "identified", "novel", "genomic", "and", "transcriptional", "associations", "among", "key", "pathogenicity", "themes", "in", "this", "group", ".", "Comparative", "genomics", "revealed", "solid", "linkage", "between", "the", "type", "I", "secretion", "system", "(", "T1SS", ")", "and", "the", "carotovoricin", "bacteriophage", "(", "Ctv", ")", "conserved", "in", "96.7", "%", "of", "Pectobacterium", "genomes", ".", "Moreover", ",", "their", "coactivation", "during", "infection", "indicates", "a", "novel", "functional", "association", "involving", "T1SS", "and", "Ctv", ".", "Another", "bacteriophage", "-", "borne", "genomic", "region", ",", "mostly", "confined", "to", "less", "than", "10", "%", "of", "Pectobacterium", "strains", ",", "was", "found", ",", "presumably", "comprising", "a", "novel", "lineage", "-", "specific", "prophage", "in", "the", "genus", ".", "We", "also", "detected", "the", "transcriptional", "coregulation", "of", "a", "previously", "predicted", "toxin", "/", "immunity", "pair", "(", "WHH", "and", "SMI1_KNR4", "families", ")", ",", "along", "with", "the", "type", "VI", "secretion", "system", "(", "T6SS", ")", ",", "which", "includes", "hcp", "and/or", "vgrG", "genes", ",", "suggesting", "a", "role", "in", "disease", "development", "as", "T6SS", "-", "dependent", "effectors", ".", "Further", ",", "we", "showed", "that", "another", "predicted", "T6SS", "-", "dependent", "endonuclease", "(", "AHH", "family", ")", "exhibited", "toxicity", "in", "ectopic", "expression", "assays", ",", "indicating", "antibacterial", "activity", ".", "Additionally", ",", "we", "report", "the", "striking", "conservation", "of", "the", "group", "4", "capsule", "(", "GFC", ")", "cluster", "in", "100", "SRE", "strains", "which", "consistently", "features", "adjacently", "conserved", "serotype", "-", "specific", "gene", "arrays", "comprising", "a", "previously", "unknown", "organization", "in", "GFC", "clusters", ".", "Also", ",", "extensive", "sequence", "variations", "found", "in", "gfcA", "orthologs", "suggest", "a", "serotype", "-", "specific", "role", "in", "the", "GfcABCD", "machinery", ".", "IMPORTANCE", "Despite", "the", "considerable", "loss", "inflicted", "on", "important", "crops", "yearly", "by", "Pectobacterium", "and", "Dickeya", "diseases", ",", "investigations", "on", "key", "virulence", "and", "interbacterial", "competition", "assets", "relying", "on", "extensive", "comparative", "genomics", "are", "still", "surprisingly", "lacking", "for", "these", "genera", ".", "Such", "approaches", "become", "more", "powerful", "over", "time", ",", "underpinned", "by", "the", "growing", "amount", "of", "genomic", "information", "in", "public", "databases", ".", "In", "particular", ",", "our", "findings", "point", "to", "new", "functional", "associations", "among", "well", "-", "known", "genomic", "themes", "enabling", "alternative", "means", "of", "neutralizing", "SRE", "diseases", "through", "disruption", "of", "pivotal", "virulence", "programs", ".", "By", "elucidating", "novel", "transcriptional", "and", "genomic", "associations", ",", "this", "study", "adds", "valuable", "information", "on", "virulence", "candidates", "that", "could", "be", "decisive", "in", "molecular", "applications", "in", "the", "near", "future", ".", "The", "utilization", "of", "100", "genomes", "of", "Pectobacterium", "and", "Dickeya", "strains", "in", "this", "study", "is", "unprecedented", "for", "comparative", "analyses", "in", "these", "taxa", ",", "and", "it", "provides", "novel", "insights", "on", "the", "biology", "of", "economically", "important", "plant", "pathogens", "." ]
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28,549
[ "Noroviruses", "(", "NoV", ")", "are", "responsible", "for", "many", "shellfish", "outbreaks", ".", "Purification", "processes", "may", "be", "applied", "to", "oysters", "before", "marketing", "to", "decrease", "potential", "fecal", "pollution", ".", "This", "step", "is", "rapidly", "highly", "effective", "in", "reducing", "Escherichia", "coli", ";", "nevertheless", ",", "the", "elimination", "of", "virus", "genomes", "has", "been", "described", "to", "be", "much", "slower", ".", "It", "is", "therefore", "important", "to", "identify", "(", "i", ")", "the", "purification", "conditions", "that", "optimize", "virus", "removal", "and", "(", "ii", ")", "the", "mechanism", "involved", ".", "To", "this", "end", ",", "the", "effects", "of", "oyster", "stress", ",", "nutrients", ",", "and", "the", "presence", "of", "a", "potential", "competitor", "to", "NoV", "adhesion", "during", "purification", "were", "investigated", "using", "naturally", "contaminated", "oysters", ".", "Concentrations", "of", "NoV", "(", "genomes", ")", "and", "of", "the", "viral", "indicator", "F", "-", "specific", "RNA", "bacteriophage", "(", "FRNAPH", ";", "genomes", "and", "infectious", "particles", ")", "were", "regularly", "monitored", ".", "No", "significant", "differences", "were", "observed", "under", "the", "test", "conditions", ".", "The", "decrease", "kinetics", "of", "both", "virus", "genomes", "were", "similar", ",", "again", "showing", "the", "potential", "of", "FRNAPH", "as", "an", "indicator", "of", "NoV", "behavior", "during", "purification", ".", "The", "T90", "(", "time", "to", "reduce", "90", "%", "of", "the", "initial", "titer", ")", "values", "were", "47.8", "days", "for", "the", "genogroup", "I", "NoV", "genome", ",", "26.7", "days", "for", "the", "genogroup", "II", "NoV", "genome", ",", "and", "43.9", "days", "for", "the", "FRNAPH", "-", "II", "genome", ".", "Conversely", ",", "monitoring", "of", "the", "viral", "genomes", "could", "not", "be", "used", "to", "determine", "the", "behavior", "of", "infectious", "viruses", "because", "the", "T90", "values", "were", "more", "than", "two", "times", "lower", "for", "infectious", "FRNAPH", "(", "20.6", "days", ")", "compared", "to", "their", "genomes", "(", "43.9", "days", ")", ".", "Finally", ",", "this", "study", "highlighted", "that", "viruses", "are", "primarily", "inactivated", "in", "oysters", "rather", "than", "released", "in", "the", "water", "during", "purification", "processes", ".", "IMPORTANCE", "This", "study", "provides", "new", "data", "about", "the", "behavior", "of", "viruses", "in", "oysters", "under", "purification", "processes", "and", "about", "their", "elimination", "mechanism", ".", "First", ",", "a", "high", "correlation", "has", "been", "observed", "between", "F", "-", "specific", "RNA", "bacteriophages", "of", "subgroup", "II", "(", "FRNAPH", "-", "II", ")", "and", "norovirus", "(", "NoV", ")", "in", "oysters", "impacted", "by", "fecal", "contamination", "when", "both", "are", "detected", "using", "molecular", "approaches", ".", "Second", ",", "when", "using", "reverse", "transcription", "-", "quantitative", "PCR", "and", "culture", "to", "detect", "FRNAPH", "-", "II", "genomes", "and", "infectious", "FRNAPH", "in", "oysters", ",", "respectively", ",", "it", "appears", "that", "genome", "detection", "provides", "limited", "information", "about", "the", "presence", "of", "infectious", "particles", ".", "The", "comparison", "of", "both", "genomes", "and", "infectious", "particles", "highlights", "that", "the", "main", "mechanism", "of", "virus", "elimination", "in", "oysters", "is", "inactivation", ".", "Finally", ",", "this", "study", "shows", "that", "none", "of", "the", "conditions", "tested", "modify", "virus", "removal", "." ]
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33,029
[ "Escherichia", "coli", "is", "a", "preferred", "strain", "for", "recombinant", "protein", "production", ",", "however", ",", "it", "is", "often", "plagued", "by", "phage", "infection", "during", "experimental", "studies", "and", "industrial", "fermentation", ".", "While", "the", "existing", "methods", "of", "obtaining", "phage", "-", "resistant", "strains", "by", "natural", "mutation", "are", "not", "efficient", "enough", "and", "time", "-", "consuming", ".", "Herein", ",", "a", "high", "-", "throughput", "method", "by", "combining", "Tn5", "transposon", "mutation", "and", "phage", "screening", "was", "used", "to", "produce", "Escherichia", "coli", "BL21", "(", "DE3", ")", "phage", "-", "resistant", "strains", ".", "Mutant", "strains", "PR281", "-", "7", ",", "PR338", "-", "8", ",", "PR339", "-", "3", ",", "PR340", "-", "8", ",", "and", "PR347", "-", "9", "were", "obtained", ",", "and", "they", "could", "effectively", "resist", "phage", "infection", ".", "Meanwhile", ",", "they", "had", "good", "growth", "ability", ",", "did", "not", "contain", "pseudolysogenic", "strains", ",", "and", "were", "controllable", ".", "The", "resultant", "phage", "-", "resistant", "strains", "maintained", "the", "capabilities", "of", "producing", "recombinant", "proteins", "since", "no", "difference", "in", "mCherry", "red", "fluorescent", "protein", "expression", "was", "found", "in", "phage", "-", "resistant", "strains", ".", "Comparative", "genomics", "showed", "that", "PR281", "-", "7", ",", "PR338", "-", "8", ",", "PR339", "-", "3", ",", "and", "PR340", "-", "8", "mutated", "in", "ecpE", ",", "nohD", ",", "nrdR", ",", "and", "livM", "genes", ",", "respectively", ".", "In", "this", "work", ",", "a", "strategy", "was", "successfully", "developed", "to", "obtain", "phage", "-", "resistant", "strains", "with", "excellent", "protein", "expression", "characteristics", "by", "Tn5", "transposon", "mutation", ".", "This", "study", "provides", "a", "new", "reference", "to", "solve", "the", "phage", "contamination", "problem", "." ]
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16,347
[ "The", "first", "and", ",", "to", "date", ",", "only", "extrachromosomal", "circular", "replicon", "identified", "in", "the", "spirochete", "Leptospira", "is", "the", "LE1", "prophage", "from", "Leptospira", "biflexa", ".", "The", "74", "-", "kb", "LE1", "genome", "has", "a", "GC", "content", "of", "36", "%", ",", "which", "is", "similar", "to", "the", "GC", "content", "of", "Leptospira", "spp", ".", "Most", "of", "the", "79", "predicted", "open", "reading", "frames", "(", "ORFs", ")", "showed", "no", "similarities", "to", "known", "ORFs", ".", "However", "21", "ORFs", "appeared", "to", "be", "organized", "in", "clusters", "that", "could", "code", "for", "head", "and", "tail", "structural", "proteins", "and", "immunity", "repressor", "proteins", ".", "In", "addition", ",", "the", "pattern", "of", "gene", "expression", "showed", "that", "several", "LE1", "genes", "are", "expressed", "specifically", "either", "in", "LE1", "prophage", "or", "in", "L.", "biflexa", "late", "after", "infection", ".", "Since", "the", "LE1", "prophage", "replicates", "autonomously", "as", "a", "circular", "replicon", "in", "L.", "biflexa", ",", "we", "were", "able", "to", "engineer", "an", "L.", "biflexa", "-", "Escherichia", "coli", "shuttle", "vector", "from", "a", "5.3", "-", "kb", "DNA", "fragment", "of", "LE1", "(", "Saint", "Girons", "et", "al", ".", ",", "J.", "Bacteriol", ".", "182:5700", "-", "5705", ",", "2000", ")", ",", "opening", "this", "genus", "to", "genetic", "manipulation", ".", "In", "this", "study", ",", "base", "compositional", "asymmetry", "confirms", "the", "location", "of", "the", "LE1", "replication", "region", "and", "suggests", "that", "LE1", "replicates", "via", "a", "bidirectional", "Theta", "-", "like", "replication", "mechanism", "from", "this", "unique", "origin", ".", "By", "subcloning", "experiments", ",", "the", "replication", "region", "can", "be", "narrowed", "down", "to", "a", "1", "-", "kb", "region", ".", "This", "minimal", "replication", "region", "consists", "of", "a", "rep", "encoding", "a", "protein", "of", "180", "amino", "acids", ".", "Upstream", "from", "rep", ",", "putative", "partitioning", "genes", ",", "called", "parA", "and", "parB", ",", "were", "found", "to", "be", "similar", "to", "the", "par", "loci", "in", "Borrelia", "plasmids", ".", "A", "significant", "increase", "of", "plasmid", "stability", "in", "L.", "biflexa", "can", "be", "seen", "only", "when", "both", "parA", "and", "parB", "are", "present", ".", "These", "results", "enable", "the", "construction", "of", "new", "shuttle", "vectors", "for", "studying", "the", "genetics", "of", "Leptospira", "spp", ".", "This", "study", "will", "also", "contribute", "to", "a", "better", "knowledge", "of", "phages", "unrelated", "to", "lambdoid", "phages", "." ]
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23,555
[ "Here", "we", "hypothesized", "that", "dormant", "cells", "of", "Mycobacterium", "tuberculosis", "(", "M.", "tuberculosis", ")", "may", "be", "resuscitated", "by", "a", "new", "expression", "system", "of", "recombinant", "mycobacteriophage", "-", "resuscitation", "-", "promoting", "factor", "(", "Rpf", ")", ".", "In", "this", "system", ",", "gene", "of", "targeted", "Rpf", "was", "cloned", "into", "mycobacteriophage", "genome", ",", "since", "mycobacteriophages", "possess", "several", "characteristics", ",", "including", "automatic", "identification", "and", "specific", "infection", "of", "M.", "tuberculosis", ".", "Thus", "the", "targeted", "delivery", "and", "endogenous", "expression", "of", "Rpf", "to", "the", "infected", "area", "of", "M.", "tuberculosis", "can", "be", "realized", ",", "followed", "by", "resuscitating", "the", "dormant", "cells", "of", "M.", "tuberculosis", ".", "Finally", ",", "these", "resuscitated", "M.", "tuberculosis", "can", "be", "thoroughly", "killed", "by", "a", "strong", "short", "-", "term", "subsequent", "chemotherapy", ",", "which", "makes", "the", "course", "of", "TB", "chemotherapy", "much", "shorter", "in", "the", "future", "compared", "to", "simple", "chemotherapy", ".", "Early", "studies", "have", "confirmed", "that", "dormant", "cells", "of", "M.", "tuberculosis", "can", "be", "resuscitated", "by", "Rpf", "in", "vitro", ",", "but", "so", "far", ",", "there", "is", "no", "report", "that", "Rpf", "can", "succeed", "in", "resuscitating", "dormant", "cells", "of", "M.", "tuberculosis", "in", "vivo", ",", "the", "reason", "may", "be", "that", "it", "is", "difficult", "for", "purified", "Rpf", "to", "remain", "active", "in", "vivo", ",", "especially", "to", "achieve", "targeted", "delivery", "of", "exogenous", "Rpf", "to", "the", "infected", "area", "of", "dormant", "cells", "of", "M.", "tuberculosis", ".", "Mycobacteriophage", "is", "a", "virus", ",", "capable", "of", "specifically", "identifying", "and", "infecting", "mycobacterium", ",", "such", "as", "M.", "tuberculosis", ".", "Several", "studies", "show", "that", "motif", "3", "-", "containing", "proteins", "have", "peptidoglycan", "-", "hydrolysing", "activity", "and", "that", "while", "this", "activity", "is", "not", "required", "for", "mycobacteriophage", "viability", ",", "it", "facilitates", "efficient", "infection", "and", "DNA", "injection", "of", "mycobacteriophage", "(", "including", "motif", "3", "protein", ")", "into", "stationary", "phase", "cells", ".", "Thus", "this", "expression", "system", "can", "achieve", "targeted", "delivery", "and", "endogenous", "expression", "of", "Rpf", "to", "infected", "area", "of", "dormant", "cells", "of", "M.", "tuberculosis", ".", "Finally", ",", "we", "discuss", "the", "implication", "of", "this", "recombinant", "expression", "system", "for", "shortening", "the", "course", "of", "TB", "chemotherapy", "." ]
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27,835
[ "Canine", "leishmaniosis", "(", "CanL", ")", "is", "one", "of", "the", "most", "important", "parasitic", "diseases", "found", "in", "several", "countries", "worldwide", ".", "Dogs", "are", "considered", "important", "domestic", "reservoirs", "of", "the", "parasites", ",", "being", "relevant", "in", "the", "maintenance", "of", "transmission", "cycle", "of", "the", "disease", "between", "sandflies", "and", "humans", ".", "However", ",", "the", "prevalence", "of", "asymptomatic", "infection", "is", "considerably", "higher", "than", "that", "of", "apparent", "clinical", "illness", "in", "the", "infected", "animals", ";", "thus", "making", "promptly", "necessary", "to", "diagnose", "the", "infection", "in", "these", "animals", ",", "which", "could", "help", "to", "allow", "to", "the", "adoption", "of", "more", "efficient", "control", "measures", "against", "disease", ".", "Parasitological", "tests", ",", "which", "are", "considered", "as", "gold", "standard", "to", "demonstrate", "the", "infection", "and", "diagnose", "the", "disease", ",", "present", "problems", "related", "with", "their", "sensitivity", ".", "Also", ",", "the", "sample´s", "collect", "is", "considered", "invasive", ".", "As", "consequence", ",", "serological", "tests", "could", "be", "applied", "as", "an", "additional", "tool", "to", "detect", "the", "asymptomatic", "and", "symptomatic", "CanL.", "For", "this", "purpose", ",", "distinct", "recombinant", "antigens", "have", "been", "studied", ";", "however", ",", "problems", "in", "their", "sensitivity", "and/or", "specificity", "have", "been", "still", "registered", ".", "The", "present", "review", "focus", "in", "advances", "in", "the", "identification", "of", "new", "diagnostic", "targets", "applied", "for", "the", "CanL", "diagnose", ",", "represented", "here", "by", "recombinant", "single", ",", "combined", "or", "chimeric", "proteins", ",", "as", "well", "as", "by", "peptides", "that", "mimic", "epitopes", "(", "mimotopes", ")", ";", "which", "were", "selected", "by", "means", "of", "immunoproteomics", "and", "phage", "display", "." ]
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25,864
[ "The", "prevalence", "of", "pathogenic", "bacteria", "acquiring", "multidrug", "antibiotic", "resistance", "is", "a", "global", "health", "threat", "to", "mankind", ".", "This", "has", "motivated", "a", "renewed", "interest", "in", "developing", "alternatives", "to", "conventional", "antibiotics", "including", "bacteriophages", "(", "viruses", ")", "as", "therapeutic", "agents", ".", "The", "bacterium", "Clostridium", "difficile", "causes", "colon", "infection", "and", "is", "particularly", "difficult", "to", "treat", "with", "existing", "antibiotics", ";", "phage", "therapy", "may", "offer", "a", "viable", "alternative", ".", "The", "punitive", "environment", "within", "the", "gastrointestinal", "tract", "can", "inactivate", "orally", "delivered", "phages", ".", "C.", "difficile", "specific", "bacteriophage", ",", "myovirus", "CDKM9", "was", "encapsulated", "in", "a", "pH", "responsive", "polymer", "(", "Eudragit", "®", "S100", "with", "and", "without", "alginate", ")", "using", "a", "flow", "focussing", "glass", "microcapillary", "device", ".", "Highly", "monodispersed", "core", "-", "shell", "microparticles", "containing", "phages", "trapped", "within", "the", "particle", "core", "were", "produced", "by", "in", "situ", "polymer", "curing", "using", "4", "-", "aminobenzoic", "acid", "dissolved", "in", "the", "oil", "phase", ".", "The", "size", "of", "the", "generated", "microparticles", "could", "be", "precisely", "controlled", "in", "the", "range", "80", "μm", "to", "160", "μm", "through", "design", "of", "the", "microfluidic", "device", "geometry", "and", "by", "varying", "flow", "rates", "of", "the", "dispersed", "and", "continuous", "phase", ".", "In", "contrast", "to", "free", "'", "naked", "'", "phages", ",", "those", "encapsulated", "within", "the", "microparticles", "could", "withstand", "a", "3", "h", "exposure", "to", "simulated", "gastric", "fluid", "at", "pH", "2", "and", "then", "underwent", "a", "subsequent", "pH", "triggered", "burst", "release", "at", "pH", "7", ".", "The", "significance", "of", "our", "research", "is", "in", "demonstrating", "that", "C.", "difficile", "specific", "phage", "can", "be", "formulated", "and", "encapsulated", "in", "highly", "uniform", "pH", "responsive", "microparticles", "using", "a", "microfluidic", "system", ".", "The", "microparticles", "were", "shown", "to", "afford", "significant", "protection", "to", "the", "encapsulated", "phage", "upon", "prolonged", "exposure", "to", "an", "acid", "solution", "mimicking", "the", "human", "stomach", "environment", ".", "Phage", "encapsulation", "and", "subsequent", "release", "kinetics", "revealed", "that", "the", "microparticles", "prepared", "using", "Eudragit", "®", "S100", "formulations", "possess", "pH", "responsive", "characteristics", "with", "phage", "release", "triggered", "in", "an", "intestinal", "pH", "range", "suitable", "for", "therapeutic", "purposes", ".", "The", "results", "reported", "here", "provide", "proof", "-", "of", "-", "concept", "data", "supporting", "the", "suitability", "of", "our", "approach", "for", "colon", "targeted", "delivery", "of", "phages", "for", "therapeutic", "purposes", "." ]
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16,086
[ "Despite", "a", "wealth", "of", "experimental", "evidence", "concerning", "the", "efficacy", "of", "the", "biocidal", "action", "associated", "with", "the", "TiO(2", ")", "photocatalytic", "reaction", ",", "our", "understanding", "of", "the", "photochemical", "mechanism", "of", "this", "particular", "biocidal", "action", "remains", "largely", "unclear", ".", "It", "is", "generally", "accepted", "that", "the", "hydroxyl", "radical", "(", ".OH", ")", ",", "which", "is", "generated", "on", "the", "surface", "of", "UV", "-", "illuminated", "TiO(2", ")", ",", "plays", "the", "main", "role", ".", "However", ",", "our", "understanding", "of", "the", "exact", "mode", "of", "action", "of", "the", "hydroxyl", "radical", "in", "killing", "microorganisms", "is", "far", "from", "complete", ",", "and", "some", "studies", "report", "that", "other", "reactive", "oxygen", "species", "(", "ROS", ")", "(", "H(2)O(2", ")", "and", "O(2).(-", ")", ",", "etc", ".", ")", "also", "play", "significant", "roles", ".", "In", "particular", ",", "whether", "hydroxyl", "radicals", "remain", "bound", "to", "the", "surface", "or", "diffuse", "into", "the", "solution", "bulk", "is", "under", "active", "debate", ".", "In", "order", "to", "examine", "the", "exact", "mode", "of", "action", "of", "ROS", "in", "inactivating", "the", "microorganism", ",", "we", "tested", "and", "compared", "the", "levels", "of", "photocatalytic", "inactivation", "of", "MS-2", "phage", "and", "Escherichia", "coli", "as", "representative", "species", "of", "viruses", "and", "bacteria", ",", "respectively", ".", "To", "compare", "photocatalytic", "microbial", "inactivation", "with", "the", "photocatalytic", "chemical", "degradation", "reaction", ",", "para", "-", "chlorobenzoic", "acid", ",", "which", "rapidly", "reacts", "with", "a", "hydroxyl", "radical", "with", "a", "diffusion", "-", "limited", "rate", ",", "was", "used", "as", "a", "probe", "compound", ".", "Two", "different", "hydroxyl", "radical", "scavengers", ",", "tert", "-", "butanol", "and", "methanol", ",", "and", "an", "activator", "of", "the", "bulk", "phase", "hydroxyl", "radical", "generation", ",", "Fe(2", "+", ")", ",", "were", "used", "to", "investigate", "their", "effects", "on", "the", "photocatalytic", "mode", "of", "action", "of", "the", "hydroxyl", "radical", "in", "inactivating", "the", "microorganism", ".", "The", "results", "show", "that", "the", "biocidal", "modes", "of", "action", "of", "ROS", "are", "very", "different", "depending", "on", "the", "specific", "microorganism", "involved", ",", "although", "the", "reason", "for", "this", "is", "not", "clear", ".", "It", "seems", "that", "MS-2", "phage", "is", "inactivated", "mainly", "by", "the", "free", "hydroxyl", "radical", "in", "the", "solution", "bulk", "but", "that", "E.", "coli", "is", "inactivated", "by", "both", "the", "free", "and", "the", "surface", "-", "bound", "hydroxyl", "radicals", ".", "E.", "coli", "might", "also", "be", "inactivated", "by", "other", "ROS", ",", "such", "as", "O(2).(-", ")", "and", "H(2)O(2", ")", ",", "according", "to", "the", "present", "results", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
412
[ "Treatment", "of", "the", "lysogenic", "strain", "M.", "lysodeikticus", "53", "-", "40", "(", "N5", ")", "with", "ethyl", "methylaminosulfonate", "results", "in", "a", "slight", "increase", "in", "infective", "center", "concentration", "of", "N5", "phages", "which", "is", "only", "detectable", "once", "disturbing", "cells", "had", "been", "eliminated", "by", "lysozyme", ".", "After", "conversion", "of", "ethyl", "methylaminosulfonate", "with", "radioactive", "labelled", "guanosine", "at", "37", "degrees", "C", ",", "N7", "-", "ethyl", "-", "guanine", "could", "be", "ascertained", ".", "Therefore", "the", "biological", "activity", "of", "the", "drug", "may", "be", "due", "to", "an", "ethylation", "of", "DNA", "." ]
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28,090
[ "Bacteriophages", "(", "phages", ")", "can", "play", "a", "useful", "role", "as", "narrow", "spectrum", "antimicrobials", "in", "food", "safety", "and", "in", "food", "production", ".", "Consumer", "attitudes", "towards", "traditional", "additives", "have", "led", "to", "a", "search", "for", "natural", ",", "potentially", "clean", "label", ",", "alternatives", ".", "At", "the", "same", "time", ",", "the", "rise", "in", "antimicrobial", "resistance", "has", "created", "a", "need", "for", "alternative", "antimicrobials", "for", "disease", "prevention", "and", "treatment", "in", "animal", "husbandry", ".", "Phages", "represent", "a", "viable", "option", "for", "both", "of", "these", "applications", ".", "We", "highlight", "important", "barriers", "which", "should", "be", "considered", "to", "improve", "the", "chance", "of", "a", "positive", "outcome", "when", "using", "phages", "in", "food", "and", "food", "production", ".", "These", "include", "the", "feasibility", "of", "adding", "high", "concentrations", "of", "phages", ",", "the", "physico", "-", "chemical", "properties", "of", "the", "food", "or", "target", ",", "how", "and", "when", "phages", "are", "applied", ",", "and", "which", "phages", "are", "chosen", "." ]
[ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 ]
14,331
[ "A", "new", "method", "for", "hybridization", "analysis", "of", "nucleic", "acids", "is", "proposed", "on", "the", "basis", "of", "the", "ability", "of", "site", "-", "specific", "nickases", "to", "cleave", "only", "one", "DNA", "strand", ".", "The", "method", "is", "based", "on", "the", "use", "of", "a", "labeled", "oligonucleotide", "with", "the", "recognition", "site", "of", "the", "nickase", "hybridized", "with", "the", "target", "(", "DNA", "or", "RNA", ")", "at", "an", "optimal", "temperature", "of", "the", "enzyme", "(", "55", "degrees", "C", ")", ".", "The", "two", "shorter", "oligonucleotides", "formed", "after", "the", "cleavage", "with", "the", "nickase", "do", "not", "complex", "with", "the", "target", ".", "Thus", ",", "a", "multiple", "cleavage", "of", "the", "labeled", "oligonucleotide", "takes", "place", "on", "one", "target", "molecule", ".", "The", "cleavage", "of", "the", "nucleotide", "is", "recorded", "either", "by", "polyacrylamide", "gel", "electrophoresis", "(", "when", "a", "radioactive", "labeled", "oligonucleotide", "is", "used", ")", "or", "by", "fluorescence", "measurements", "(", "if", "the", "oligonucleotide", "has", "the", "structure", "of", "a", "molecular", "beacon", ")", ".", "The", "new", "method", "was", "tested", "on", "nickase", "BspD6I", "and", "a", "radioactive", "oligonucleotide", "complementary", "to", "the", "polylinker", "region", "of", "the", "viral", "DNA", "strand", "in", "bacteriophage", "M13mp19", ".", "Unfortunately", ",", "nickase", "BspD6I", "does", "not", "cleave", "DNA", "in", "the", "RNA", "-", "DNA", "duplexes", "and", "therefore", "can", "not", "be", "used", "for", "detection", "of", "RNA", "targets", "." ]
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27,916
[ "Pseudomonas", "aeruginosa", "is", "an", "opportunistic", "pathogen", "with", "a", "capacity", "to", "develop", "antibiotic", "resistance", ",", "which", "underlies", "a", "larger", "proportion", "of", "hospital", "-", "acquired", "infections", "and", "higher", "morbidity", "and", "mortality", ",", "compared", "to", "other", "bacterial", "infections", ".", "Effective", "novel", "approaches", "for", "treatment", "of", "infections", "induced", "by", "this", "pathogen", "are", "therefore", "necessary", ".", "Phage", "therapy", "represents", "a", "promising", "alternative", "solution", "to", "eradicate", "antibiotic", "-", "resistant", "pathogens", ".", "Here", ",", "we", "investigated", "phage", "protein", "efficacy", "against", "multi", "-", "drug", "resistant", "(", "MDR", ")", "P.", "aeruginosa", "PAR21", "and", "PAR50", "strains", "isolated", "from", "diabetic", "foot", "ulcer", "patients", ".", "The", "results", "obtained", "using", "spot", "assay", ",", "zymography", ",", "spectrophotometry", "and", "scanning", "electron", "microscopy", "at", "low", "voltage", "(", "SEM", "-", "LV", ")", "indicate", "that", "the", "phage", "protein", ",", "PA", "-", "PP", ",", "exerts", "activity", "against", "P.", "aeruginosa", "PAR50", "while", "having", "no", "impact", "on", "the", "PAR21", "strain", ".", "Using", "LC", "-", "MS", "-", "MS", "/", "MS", "and", "comparative", "analysis", "of", "the", "peptide", "molecular", "mass", "with", "the", "protein", "sequence", "database", ",", "PA", "-", "PP", "was", "identified", "as", "a", "member", "of", "the", "serine", "protease", "family", ",", "a", "result", "corroborated", "by", "its", "ability", "to", "digest", "casein", ".", "We", "additionally", "showed", "a", "capacity", "of", "PA", "-", "PP", "to", "digest", "porin", "protein", "on", "the", "bacterial", "outer", "membrane", "(", "OM", ")", ".", "Moreover", ",", "synergistic", "activity", "between", "PA", "-", "PP", "protein", "and", "piperacillin", "led", "to", "higher", "sensitivity", "of", "bacterial", "cells", "to", "this", "antibiotic", ".", "Our", "collective", "findings", "suggest", "that", "PA", "-", "PP", "targets", "porin", "protein", "on", "PAR50", "OM", ",", "thereby", "increasing", "its", "sensitivity", "to", "specific", "antibiotics", ".", "The", "adverse", "effects", "observed", "on", "bacterial", "cells", "using", "SEM", "-", "LV", "suggest", "further", "roles", "of", "this", "protein", "that", "remain", "to", "be", "established", "." ]
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3,376
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Dataset Card for "ner_vir_naeus_dataset"

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