Bacterial LomR Induces the Vibriophage VP882 VqmA-Directed Quorum-Sensing Lysogeny-Lysis Transition

Abstract

The bacterial cell-cell communication process called quorum sensing enables groups of bacteria to synchronously alter behavior in response to changes in cell population density. Quorum sensing relies on the production, release, accumulation, and detection of extracellular signal molecules called autoinducers. Here, we investigate a mechanism employed by a vibriophage to surveil host quorum sensing and tune its lysogeny-lysis decision to host cell density. The phage possesses a gene called vqmAPhage encoding a quorum-sensing receptor homologous to vibrio VqmA. Both VqmA receptors can detect the host bacteria-produced autoinducer called DPO. DPO-bound VqmAPhage launches the phage lysis process. We discover that the bacterial host produces an inducer of the VqmAPhage-directed quorum-sensing lysogeny-lysis transition. Production of the inducer appears to be widespread among bacteria. A screen of the Escherichia coli Keio collection for mutants impaired for inducer production revealed lomR, located in a prophage, and encoding a poorly understood protein. In the E. coli screening strain, lomR is interrupted by DNA encoding an insertion element. The 3 domain of this LomR protein is sufficient to induce VqmAPhage-directed lysis. Alanine-scanning mutagenesis showed that substitution at either of two key residues abrogates inducer activity. Full-length LomR is similar to the outer membrane porin OmpX in E. coli and Vibrio parahaemolyticus O3:K6, and OmpT in Vibrio cholerae C6706, and indeed, OmpX and OmpT can induce VqmAPhage-directed activity. Possibly, development of the LomR, OmpX, or OmpT proteins as tools to direct phage lysis of host cells could be used to control bacteria in medical or industrial settings. ABSTRACT IMPORTANCEBacteria communicate with chemical signal molecules using a process called quorum sensing. Quorum sensing allows bacteria to track their cell numbers and orchestrate collective behaviors. Recently, we discovered that a virus that infects and kills bacteria "eavesdrops" on its hosts quorum-sensing process. Specifically, the virus monitors host cell growth by detecting the accumulation of host quorum-sensing signal molecules. In response to the garnered quorum-sensing information, the virus kills the host bacterial cells when the bacterial population has reached a high cell density. This strategy presumably enhances transmission of viruses to new host cells. Here, we discover and characterize three closely-related bacterial host-produced proteins called LomR, OmpX, and OmpT that are capable of inducing the viral quorum-sensing-mediated killing program. Development of this class of inducer proteins as tools to drive "on demand" virus-mediated lysis of pathogenic host bacterial cells could be used to control bacteria in medical or industrial settings.