Vibrio parahaemolyticus quorum sensing controls phage VP882 transmission

Abstract Quorum sensing is a cell-to-cell communication process bacteria use to orchestrate collective behaviors. Quorum sensing involves the production, release, and detection of extracellular signal molecules called autoinducers. Some temperate phages can monitor bacterial autoinducers enabling them to track the abundance of potential host cells in the vicinity. Quorum-sensing-responsive phages can preferentially launch the transition from lysogeny to lytic replication at high cell density, presumably maximizing transmission. Once the phage lytic program is enacted, if nearby host cells are already lysogens, infections initiated by released virions could be nonproductive due to homoimmunity or superinfection exclusion mechanisms, posing a conundrum for temperate phages, including those that surveil quorum-sensing autoinducers. Here, we define host and phage components that influence transmission of the first discovered quorum-sensing-responsive phage, phage VP882, in populations of its host, Vibrio parahaemolyticus. We show that phage VP882 uses the K-antigen of serotype O3:K6 as its receptor. We demonstrate that host cells can prevent phage access to the O3:K6 K-antigen via quorum-sensing-control of the export of polysaccharides that shield the K-antigen from the phage at high cell density. We discover that phage VP882 can superinfect and superlysogenize V. parahaemolyticus, overcoming the challenge of detecting whether or not potential hosts are lysogens. Following superlysogenization, recombination of the resident and newly infecting phage genomes can occur possibly promoting phage VP882 genome diversification. Importance A longstanding mystery is how temperate phages optimally time the launch of their lytic cascades to maximize spread. Quorum-sensing-responsive phages can preferentially execute their lytic replication programs at high host cell density, which in principle should foster transmission. However, if nearby host cells are already lysogens, infections initiated by released virions could be nonproductive due to homoimmunity or superinfection exclusion. We define host and phage components influencing transmission of the quorum-sensing-responsive phage VP882 in Vibrio parahaemolyticus populations. Phage VP882 uses the O3:K6 K-antigen as its receptor. Host cells prevent phage infection via quorum-sensing-controlled export of polysaccharides that shield the K-antigen at high cell density. We discover that phage VP882 can superinfect and superlysogenize V. parahaemolyticus, overcoming the challenge of detecting whether or not potential hosts are lysogens. These findings reveal how phages can capitalize on interception of host quorum-sensing cues to maximize their reproductive success. Competing Interest Statement The authors have declared no competing interest. Footnotes This version of the manuscript has been updated to match the latest submitted version.