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Phage Wars: the molecular interactions underlying the arms race between a lytic bacteriophage and epidemic Vibrio cholerae

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Abstract

Viruses infect all living organisms, and in response, hosts have had to adapt to the constant threat of viral infection. The interactions between viruses and their hosts shape the evolutionary trajectory of both entities over time. Phages, which are viruses that infect bacteria, are the most prevalent infectious agents and can vastly outnumber their bacterial hosts in a given environment. One such target of phage predation is the pathogen Vibrio cholerae, which can be co-isolated with phages both from cholera patient stool samples, as well as from aquatic reservoirs in regions where cholera is endemic. Analysis of the phages that are shed in cholera patient stools indicates that one phage, ICP1, is the most dominant phage that infects epidemic V. cholerae, at least in Bangladesh. In response to the constant threat of infection, epidemic V. cholerae has acquired an anti-phage island, referred to as PLE, that specifically blocks ICP1 infection. Here, we use the interactions between ICP1 and V. cholerae PLE as a model system to examine the molecular interactions between a virulent phage and its bacterial host. Using natural isolates enables us to comprehend the ways in which this molecular arms race has influenced the evolution of both ICP1 and epidemic V. cholerae. In the first chapter, we identify the molecular specificity of the PLE response to ICP1 during infection, demonstrating that this anti-phage island is highly evolved to activate only in response to the dominant phage ICP1. In the second chapter, we identify additional ICP1-PLE molecular interactions that facilitate PLE escape from ICP1-mediated host takeover processes. In the third chapter, we examine the ICP1-encoded CRISPR-Cas adaptive immune system that is specifically deployed to processively degrade PLE and allow for ICP1 to productively infect the PLE (+) V. cholerae host. Overall, the work presented here updates our understanding of the mechanisms by which anti-phage islands, such as PLE, have the capacity to exploit their predatory phage to mobilize and influence the evolution of pathogenic populations.

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This item is under embargo until August 5, 2023.