A family of linear plasmid phages that detect a quorum-sensing autoinducer exists in multiple bacterial species

ABSTRACT Temperate phages oscillate between lysogeny, a genomic maintenance state within a bacterial host, and lytic replication, in which the host is killed, and newly made phage particles are released. Successful transmission to new hosts requires that temperate phages appropriately time their transitions from lysogeny to lysis. It is well understood that temperate phages trigger lysis upon detection of host cell stress. Understanding of the breadth of cues that induce lysis expanded with the discovery of phages carrying quorum-sensing receptor genes that promote lytic induction exclusively at high host cell density. Bacteria engage in a cell-cell communication process called quorum sensing, which relies on the production, release, accumulation, and group-wide detection of extracellular signal molecules called autoinducers. Bacteria use quorum sensing to monitor changes in population density and synchronize collective behaviors. The temperate phage VP882 (φVP882) encodes VqmAφ – a homolog of its host’s quorum-sensing receptor/transcription factor VqmA. VqmAφ allows φVP882 to detect the accumulation of the host autoinducer called DPO. Presumably, launching the lytic induction program at high host cell density maximizes φVP882 transmission to new hosts. Here, by mining sequence databases for linear plasmid phages, we identify VP882-like phages in multiple DPO-producing bacterial species isolated at diverse times and geographic locations. We show that the VqmAφ homologs can indeed detect DPO and, in response, activate the lytic pathway. Our observation indicates that φVP882 is a member of a large family of globally-dispersed quorum-sensing-responsive temperate phages. IMPORTANCE The discovery of quorum-sensing responsive linear plasmid phages has transformed understanding of phage-bacterial interactions by demonstrating inter-domain chemical communication. To date, however, examples of quorum-sensing responsive phages have been sparse. The founding example of such a phage, φVP882, detects a chemical communication signal molecule called DPO that is produced by diverse bacterial species. We investigated whether a family of VP882-like phages might exist that detect and respond to DPO. We find that indeed, VP882-like phages reside in DPO-producing bacterial species isolated at different times and geographic locations, suggesting their wide circulation in the environment. This observation strengthens the evidence for the generality of phage-bacterial inter-domain chemical communication.