Roles of the Site 2 Protease Eep in Staphylococcus aureus.

In , the site 2 protease Eep generates sex pheromones, including cAM373. Intriguingly, in , a peptide similar to cAM373, named cAM373_SA, is produced from the gene. Here, we report that the staphylococcal Eep homolog is not only responsible for the production of cAM373_SA but also critical for staphylococcal virulence. As with other Eep proteins, the staphylococcal Eep protein has four transmembrane (TM) domains, with the predicted zinc metalloprotease active site (HEXXH) in the first TM domain. deletion reduced the cAM373_SA activity in the culture supernatant to the level of the deletion mutant. It also markedly decreased the cAM373 peptide peak in a high-performance liquid chromatography (HPLC) analysis. Proteomics analysis showed that Eep affects the production and/or the release of diverse proteins, including the signal peptidase subunit SpsB and the surface proteins SpA, SasG, and FnbA. deletion decreased the adherence of to host epithelial cells; however, the adherence of the mutant was increased by overexpression of the surface proteins SpA, SasG, and FnbA. deletion reduced staphylococcal resistance to killing by human neutrophils as well as survival in a murine model of blood infection. The overexpression of the surface protein SpA in the mutant increased bacterial survival in the liver. Our study illustrates that in , Eep not only generates cAM373_SA but also contributes to the survival of the bacterial pathogen in the host. The emergence of multidrug-resistant makes the treatment of staphylococcal infections much more difficult. can acquire a drug resistance gene from other bacteria, such as Intriguingly, produces a sex pheromone for the plasmid pAM373, raising the possibility that actively promotes plasmid conjugation from In this study, we found that the staphylococcal Eep protein is responsible for sex pheromone processing and contributes to the survival of the bacteria in the host. These results will enhance future research on the drug resistance acquisition of and can lead to the development of novel antivirulence drugs.