SpdC, a novel virulence factor, controls histidine kinase activity in Staphylococcus aureus

• DOI: 10.1371/journal.ppat.1006917
• Publication Date: 2018-03-15T17:57:38Z
• Authors: Olivier Poupel; Caroline Proux; Bernd Jagla; Tarek Msadek; Sarah Dubrac
• Keywords: Regulon; Histidine kinase; Virulence factor; Lysostaphin; Lipid II; Autolysin

The success of Staphylococcus aureus, as both a human and animal pathogen, stems from its ability to rapidly adapt wide spectrum environmental conditions. Two-component systems (TCSs) play crucial role in this process. Here, we describe novel staphylococcal virulence factor, SpdC, an Abi-domain protein, involved signal sensing and/or transduction. We have uncovered functional link between the WalKR essential TCS SpdC Abi membrane protein. Expression spdC is positively regulated by system and, turn, negatively controls regulon genes, effectively constituting negative feedback loop. mainly controlling cell wall metabolism through regulation autolysin production. shown that inhibits WalKR-dependent synthesis four peptidoglycan hydrolases, SceD, SsaA, LytM AtlA, well impacting S. aureus resistance towards lysostaphin antibiotics such oxacillin tunicamycin. also required for biofilm formation murine septicemia model. Using protein-protein interactions E. coli subcellular localization showed WalK kinase are localized at division septum two proteins interact. In addition WalK, our results indicate interacts with nine other histidine kinases, suggesting protein may act global regulator activity. Indeed, using RNA-Seq analysis, expression approximately one hundred genes many which belong regulons.