Phage predation, disease severity, and pathogen genetic diversity in cholera patients

Science. 2024 Apr 19;384(6693):eadj3166. doi: 10.1126/science.adj3166. Epub 2024 Apr 19.

Abstract

Despite an increasingly detailed picture of the molecular mechanisms of bacteriophage (phage)-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. In this work, we report a year-long, nationwide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified Vibrio cholerae (prey) and its virulent phages (predators) using metagenomics and quantitative polymerase chain reaction while accounting for antibiotic exposure using quantitative mass spectrometry. Virulent phage (ICP1) and antibiotics suppressed V. cholerae to varying degrees and were inversely associated with severe dehydration depending on resistance mechanisms. In the absence of antiphage defenses, predation was "effective," with a high predator:prey ratio that correlated with increased genetic diversity among the prey. In the presence of antiphage defenses, predation was "ineffective," with a lower predator:prey ratio that correlated with increased genetic diversity among the predators. Phage-bacteria coevolution within patients should therefore be considered in the deployment of phage-based therapies and diagnostics.

Publication types

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

MeSH terms

  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Bacteriophages* / genetics
  • Bacteriophages* / physiology
  • Bangladesh
  • Cholera* / microbiology
  • Genetic Variation*
  • Humans
  • Metagenomics
  • Severity of Illness Index
  • Vibrio cholerae* / genetics
  • Vibrio cholerae* / virology

Substances

  • Anti-Bacterial Agents