Abstract
Vibrio cholerae-specific bacteriophages are common features of the microbial community during cholera infection in humans. Phages impose strong selective pressure that favors the expansion of phage-resistant strains over their vulnerable counterparts. The mechanisms allowing virulent V. cholerae strains to defend against the ubiquitous threat of predatory phages have not been established. Here, we show that V. cholerae PLEs (phage-inducible chromosomal island-like elements) are widespread genomic islands dedicated to phage defense. Analysis of V. cholerae isolates spanning a 60-year collection period identified five unique PLEs. Remarkably, we found that all PLEs (regardless of geographic or temporal origin) respond to infection by a myovirus called ICP1, the most prominent V. cholerae phage found in cholera patient stool samples from Bangladesh. We found that PLE activity reduces phage genome replication and accelerates cell lysis following ICP1 infection, killing infected host cells and preventing the production of progeny phage. PLEs are mobilized by ICP1 infection and can spread to neighboring cells such that protection from phage predation can be horizontally acquired. Our results reveal that PLEs are a persistent feature of the V. cholerae mobilome that are adapted to providing protection from a single predatory phage and advance our understanding of how phages influence pathogen evolution.
Highlights
A chief determinant of microbial survival is protection from predation
V. cholerae is commonly recovered from patient samples with predatory bacteriophages, which impose strong selective pressure favoring phage resistant strains over their vulnerable counterparts
We investigated the activity of phage-inducible chromosomal island-like element (PLE), a novel group of mobile genetic elements that have contributed to phage resistance in V. cholerae over the last 60 years
Summary
A chief determinant of microbial survival is protection from predation. Phages are viral predators that act with exquisite specificity to kill their perpetually evolving bacterial targets. The overall success of epidemic Vibrio cholerae, the causative agent of the diarrheal disease cholera, is partly due to its ability to defend against predatory phages. Such phages are found in the aquatic environment [1] and are co-ingested with V. cholerae, permitting continued phage predation of V. cholerae within the human intestinal tract [2]. Recent molecular characterization of lytic phages associated with epidemic cholera has revealed that phage diversity is strikingly low over significant time periods, indicating that a surprisingly limited number of phage types place a significant predatory burden on V. cholerae in the context of human infection [2,3]. The O1 antigen is required for V. cholerae to efficiently colonize the small intestine [4], which places mutational constraints on V. cholerae in the human host and ensures ICP1 has access to susceptible V. cholerae in order to propagate [5]
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