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Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
Published on: June 11, 2015
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, USA.
Abstract:
Bacteria harness diverse defence systems that protect against phage predation1, many of which are encoded on horizontally transmitted mobile genetic elements2. In turn, phages evolve counter-defences3, driving a dynamic arms race that remains underexplored in human disease contexts. For the diarrhoeal pathogen Vibrio cholerae, a higher burden of its lytic phage ICP1 in patient stool correlates with reduced disease severity4. However, direct molecular evidence of lytic phages driving selection of epidemic V. cholerae has not been demonstrated. Here, through clinical surveillance in cholera-endemic Bangladesh, we capture the acquisition of a parasitic anti-phage mobile genetic element, PLE11, that initiated a selective sweep coinciding with the largest cholera outbreak in recent records. PLE11 showed potent anti-phage activity against cocirculating ICP1, explaining its rapid and dominating emergence. We identify PLE11-encoded Rta as the defence responsible and provide evidence that Rta restricts phage tail assembly. Using experimental evolution, we predict phage counteradaptations against PLE11 and document the eventual emergence and selection of clinical ICP1 that achieve a convergent evolutionary outcome. Finally, we discover how PLEs balance their dependence on ICP1 tail proteins for horizontal transmission with the restriction of phage tail assembly by Rta: PLEs construct chimeric tails composed of both mobile genetic element-encoded and phage-encoded proteins to ensure their transmission. Collectively, our findings reveal the molecular basis of the natural selection of a globally important pathogen and its virus in a clinically relevant context.
Insights
Bacteria and viruses engage in a constant evolutionary battle. A new mobile genetic element, PLE11, emerged in Vibrio cholerae, driving pathogen evolution during a major cholera outbreak by targeting the ICP1 phage.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genetics
Background:
- Bacteria possess defense systems against phage predation, often encoded on mobile genetic elements.
- Bacteriophages (phages) and bacteria engage in a dynamic evolutionary arms race, particularly relevant in human diseases.
- In Vibrio cholerae, higher ICP1 phage loads correlate with reduced diarrheal disease severity, but direct evidence of phage-driven bacterial selection was lacking.
Purpose of the Study:
- To investigate the molecular mechanisms driving the natural selection of the globally important pathogen Vibrio cholerae.
- To understand the evolutionary dynamics between Vibrio cholerae and its lytic phage ICP1 in a clinical context.
- To identify the genetic basis for the emergence and dominance of anti-phage elements during a cholera outbreak.
Main Methods:
- Clinical surveillance in cholera-endemic Bangladesh to identify mobile genetic elements.
- Experimental evolution to study phage counter-adaptations.
- Molecular characterization of the anti-phage mechanism and phage-host interactions.
- Analysis of mobile genetic element (PLE) and phage (ICP1) genome sequences.
Main Results:
- The acquisition of a parasitic anti-phage mobile genetic element, PLE11, coincided with a major Vibrio cholerae outbreak.
- PLE11 exhibited potent anti-phage activity against ICP1, mediated by the Rta protein, which restricts phage tail assembly.
- Experimental evolution revealed phage counter-adaptations, leading to the emergence of ICP1 variants capable of overcoming PLE11.
- PLEs were found to construct chimeric tails for horizontal transmission, balancing defense with propagation.
Conclusions:
- The study reveals the molecular basis for the natural selection of Vibrio cholerae, driven by phage predation and mobile genetic element-mediated defense.
- PLE11's emergence and selection demonstrate a rapid evolutionary response to phage pressure in a clinically relevant pathogen.
- The findings highlight the complex interplay between bacteria, phages, and mobile genetic elements in shaping pathogen evolution during disease outbreaks.
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