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Updated: May 27, 2025

Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
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Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins

Published on: June 11, 2015

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Capturing dynamic phage-pathogen coevolution by clinical surveillance

Yamini Mathur1, Caroline M Boyd1, Jeannette E Farnham1

  • 1Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

Biorxiv : the Preprint Server for Biology
|February 20, 2025
PubMed

Insights

Bacteria and viruses engage in a constant evolutionary battle. A mobile genetic element (MGE) called PLE11 emerged, protecting *Vibrio cholerae* from phage predation and driving pathogen evolution during a major cholera outbreak.

Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Genetics

Background:

  • Bacteria possess defense systems against phage predation, often encoded on mobile genetic elements (MGEs).
  • Phages and bacteria engage in a dynamic evolutionary arms race, particularly relevant in human disease contexts.
  • A higher burden of the lytic phage ICP1 in *Vibrio cholerae* correlates with reduced diarrheal disease severity, but direct evidence of phage-driven selection is lacking.

Purpose of the Study:

  • To investigate the molecular basis of phage-driven selection in *Vibrio cholerae* during a cholera outbreak.
  • To identify the anti-phage mechanisms and evolutionary dynamics between *V. cholerae* and its phage ICP1.

Main Methods:

  • Clinical surveillance in cholera-endemic Bangladesh to track MGE acquisition.
  • Experimental evolution to study phage counteradaptations.
  • Molecular characterization of phage-defense interactions and MGE-mediated manipulation of phage components.

Main Results:

  • The acquisition of a parasitic anti-phage MGE, PLE11, was observed, coinciding with a major cholera outbreak and a selective sweep in *V. cholerae*.
  • PLE11 provided potent anti-phage activity against ICP1 via the Rta protein, which restricts phage tail assembly.
  • Experimental evolution revealed phage counteradaptations and the emergence of ICP1 variants capable of overcoming PLE11 defenses, including the formation of chimeric phage-MGE tails.

Conclusions:

  • PLE11-mediated phage resistance drove the natural selection of *Vibrio cholerae* during a significant cholera epidemic.
  • PLEs can hijack phage structural proteins for horizontal transmission and manipulate phage tail assembly, revealing a novel mechanism of co-evolution.
  • This study elucidates the molecular underpinnings of pathogen-virus co-evolution in a clinically relevant setting.

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