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.
Highlights
Traditional views of host–pathogen interactions are of a battle between two opposing organisms
Bacteriophages influence bacterial populations in many ecosystems and temperate phages play a role in many diseases through lysogenic conversion (Brüssow et al, 2004)
In order for V. cholerae to colonize the human small intestine and elicit diarrhea, it produces a set of virulence determinants including cholera toxin (Herrington et al, 1988)
Summary
Traditional views of host–pathogen interactions are of a battle between two opposing organisms. These toxR mutants would not colonize the human small intestine and be recovered in the secretory diarrhea if ingested (Herrington et al, 1988), which further supports our conclusion that these mutants arose due to ICP2 predation during cholera infection in this individual. This indicates that, in this patient, predation and selection of phage-resistant mutants likely occurred late in infection when colonization and virulence gene expression were no longer required for the development of acute symptoms (Merrell et al, 2002). Our findings indicate that diseased states, which are often accompanied by significant bacterial proliferation, likely facilitate these predatory interactions
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