title: Evolutionary consequences of intra-patient phage predation on microbial populations.
abstract: The impact of phage predation on bacterial pathogens in the context of human disease is not currently appreciated. 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.
authors.affiliation: Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, United States.
authors.forename: Kimberley D
authors.initials: KD
authors.lastname: Seed
authors.affiliation: Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, United States.
authors.forename: Minmin
authors.initials: M
authors.lastname: Yen
authors.affiliation: Département de sciences biologiques, Université de Montréal, Montreal, Canada.
authors.forename: B Jesse
authors.initials: BJ
authors.lastname: Shapiro
authors.affiliation: Partners In Health, Boston, United States.
authors.forename: Isabelle J
authors.initials: IJ
authors.lastname: Hilaire
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, United States Department of Medicine, Harvard Medical School, Boston, United States.
authors.forename: Richelle C
authors.initials: RC
authors.lastname: Charles
authors.affiliation: Partners In Health, Boston, United States Division of Global Health Equity, Brigham and Women's Hospital, Boston, United States.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Teng
authors.affiliation: Partners In Health, Boston, United States Division of Global Health Equity, Brigham and Women's Hospital, Boston, United States Department of Global Health and Social Medicine, Harvard Medical School, Boston, United States.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Ivers
authors.affiliation: National Public Health Laboratory, Port-au-Prince, Haiti.
authors.forename: Jacques
authors.initials: J
authors.lastname: Boncy
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, United States Department of Medicine, Harvard Medical School, Boston, United States Department of Pediatrics, Harvard Medical School, Boston, United States.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Harris
authors.affiliation: Department of Molecular Biology and Microbiology, Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, United States andrew.camilli@tufts.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001435:Bacteriophages / Q000235:genetics* / Q000254:growth & development; D001459:Bangladesh / Q000453:epidemiology; D005075:Biological Evolution; D002771:Cholera / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology / Q000635:transmission; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005786:Gene Expression Regulation; D006205:Haiti / Q000453:epidemiology; D006801:Humans; D051379:Mice; D009154:Mutation; D011817:Rabbits; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014734:Vibrio cholerae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000821:virology*; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C096349:OmpU protein, Vibrio cholerae; D014157:Transcription Factors; C499324:toxR protein, Vibrio cholerae
keywords: OmpU; ToxR; Vibrio cholerae; bacteriophage; cholera; phage