ABSTRACTGram-positive bacteria process and release small peptides, or pheromones, that act as signals for the induction of adaptive traits, including those involved in pathogenesis. One class of small signaling pheromones is the cyclic autoinducing peptides (AIPs), which regulate expression of genes that orchestrate virulence and persistence in a range of microbes, including staphylococci, listeriae, clostridia, and enterococci. In a genetic screen forStaphylococcus aureussecreted virulence factors, we identified anS. aureusmutant containing an insertion in the geneSAUSA300_1984(mroQ), which encodes a putative membrane-embedded metalloprotease. A ΔmroQmutant exhibited impaired induction of Toll-like receptor 2-dependent inflammatory responses from macrophages but elicited greater production of the inflammatory cytokine interleukin-1β and was attenuated in a murine skin and soft tissue infection model. The ΔmroQmutant phenocopies anS. aureusmutant containing a deletion of the accessory gene regulatory system (Agr), wherein both strains have significantly reduced production of secreted toxins and virulence factors but increased surface protein A abundance. The Agr system controls virulence factor gene expression inS. aureusby sensing the accumulation of AIP via the histidine kinase AgrC and the response regulator AgrA. We provide evidence to suggest that MroQ acts within the Agr pathway to facilitate the optimal processing or export of AIP for signal amplification through AgrC/A and induction of virulence factor gene expression. Mutation of MroQ active-site residues significantly reduces AIP signaling and attenuates virulence. Altogether, this work identifies a new component of the Agr quorum-sensing circuit that is critical for the production ofS. aureusvirulence factors.
YeiE Regulates Motility and Gut Colonization in Salmonella enterica Serotype Typhimurium
