The Staphylococcus aureus Protein-Coding Gene gdpS Modulates sarS Expression via mRNA-mRNA Interaction

Staphylococcus aureus is an important Gram-positive pathogen responsible for numerous diseases ranging from localized skin infections to life-threatening systemic infections. The virulence ofS. aureus is essentially determined by a wide spectrum of factors, including cell wall-associated proteins and secreted toxins that are precisely controlled in response to environmental changes. GGDEF domain protein fromStaphylococcus (GdpS) is the only conserved staphylococcal GGDEF domain protein that is involved not in c-di-GMP synthesis but in the virulence regulation ofS. aureus NCTC8325. Our previous study showed that the inactivation ofgdpS generates an extensive change of virulence factors together with, in particular, a major Spa (protein A) surface protein. As reported,sarS is a direct positive regulator ofspa . The decreased transcript levels ofsarS in thegdpS mutant compared with the parental NCTC8325 strain suggest thatgdpS affectsspa through interaction withsarS . In this study, site mutation and complementary experiments showed that the translation product ofgdpS was not involved in the regulation of transcript levels ofsarS . We found thatgdpS functioned through direct RNA-RNA base pairing with the 5′ untranslated region (5′UTR) ofsarS mRNA and that a putative 18-nucleotide region played a significant role in the regulatory process. Furthermore, the mRNA half-life analysis ofsarS in thegdpS mutant showed thatgdpS positively regulates the mRNA levels ofsarS by contributing to the stabilization ofsarS mRNA, suggesting thatgdpS mRNA may regulatespa expression in an RNA-dependent pathway.