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Here, we show that predatory interactions of a phage with an important environmentally transmitted pathogen, Vibrio cholerae, can modulate the evolutionary trajectory of this pathogen during the natural course of infection within individual patients. We analyzed geographically and temporally disparate cholera patient stool samples from Haiti and Bangladesh and found that phage predation can drive the genomic diversity of intra-patient V. cholerae populations. Intra-patient phage-sensitive and phage-resistant isolates were isogenic except for mutations conferring phage resistance, and moreover, phage-resistant V. cholerae populations were composed of a heterogeneous mix of many unique mutants. We also observed that phage predation can significantly alter the virulence potential of V. cholerae shed from cholera patients. We provide the first molecular evidence for predatory phage shaping microbial community structure during the natural course of infection in humans.<\/jats:p>","DOI":"10.7554\/elife.03497","type":"journal-article","created":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T05:11:57Z","timestamp":1408684317000},"source":"Crossref","is-referenced-by-count":151,"title":["Evolutionary consequences of intra-patient phage predation on microbial populations"],"prefix":"10.7554","volume":"3","author":[{"given":"Kimberley D","family":"Seed","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minmin","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B Jesse","family":"Shapiro","sequence":"additional","affiliation":[{"name":"D\u00e9partement de sciences biologiques, Universit\u00e9 de Montr\u00e9al, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle J","family":"Hilaire","sequence":"additional","affiliation":[{"name":"Partners In Health, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richelle C","family":"Charles","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, United States"},{"name":"Department of Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica E","family":"Teng","sequence":"additional","affiliation":[{"name":"Partners In Health, Boston, United States"},{"name":"Division of Global Health Equity, Brigham and Women's Hospital, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise C","family":"Ivers","sequence":"additional","affiliation":[{"name":"Partners In Health, Boston, United States"},{"name":"Division of Global Health Equity, Brigham and Women's Hospital, Boston, United States"},{"name":"Department of Global Health and Social Medicine, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Boncy","sequence":"additional","affiliation":[{"name":"National Public Health Laboratory, Port-au-Prince, Haiti"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason B","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital, Boston, United States"},{"name":"Department of Medicine, Harvard Medical School, Boston, United States"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Camilli","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2014,8,26]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"W400","DOI":"10.1093\/nar\/gkh417","article-title":"PRED-TMBB: a web server for predicting the topology of \u03b2-barrel outer membrane proteins","volume":"32","author":"Bagos","year":"2004","journal-title":"Nucleic Acids Research"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1128\/MMBR.68.3.560-602.2004","article-title":"Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion","volume":"68","author":"Br\u00fcssow","year":"2004","journal-title":"Microbiology and Molecular Biology Reviews"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"335","DOI":"10.2217\/17460913.2.3.335","article-title":"Regulation of virulence in Vibrio cholerae: the ToxR regulon","volume":"2","author":"Childers","year":"2007","journal-title":"Future Microbiology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1056\/NEJMoa1012928","article-title":"The origin of the Haitian cholera outbreak strain","volume":"364","author":"Chin","year":"2011","journal-title":"The New England Journal of Medicine"},{"key":"bib5","article-title":"Final report of the independent panel of experts on the cholera outbreak in Haiti","author":"Cravioto","year":"2011","unstructured":"Cravioto A, Lanata CF, Lantagne DS, Nair GB. 2011. 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