Evolutionary consequences of intra-patient phage predation on microbial populations

Elife. 2014 Aug 26;3:e03497. doi: 10.7554/eLife.03497.


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.

Keywords: OmpU; ToxR; Vibrio cholerae; bacteriophage; cholera; phage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism
  • Animals
  • Animals, Newborn
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacteriophages / genetics*
  • Bacteriophages / growth & development
  • Bangladesh / epidemiology
  • Biological Evolution
  • Cholera / epidemiology
  • Cholera / microbiology*
  • Cholera / pathology
  • Cholera / transmission
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Feces / microbiology
  • Gene Expression Regulation
  • Haiti / epidemiology
  • Humans
  • Mice
  • Mutation
  • Rabbits
  • Severity of Illness Index
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vibrio cholerae / genetics
  • Vibrio cholerae / immunology
  • Vibrio cholerae / pathogenicity*
  • Vibrio cholerae / virology*
  • Virulence


  • Adhesins, Bacterial
  • Bacterial Proteins
  • DNA-Binding Proteins
  • OmpU protein, Vibrio cholerae
  • Transcription Factors
  • toxR protein, Vibrio cholerae