MgrA negatively impacts Staphylococcus aureus invasion by regulating capsule and FnbA

Virulence genes are regulated by a complex regulatory network in Staphylococcus aureus. Some of the regulators are global in nature that affect many downstream genes. MgrA is a multiple gene regulator that has been shown to activate genes involved in capsule biosynthesis and repress surface protein genes. The goal of this study is to demonstrate the biological significance of MgrA regulation of capsule and surface proteins. We found strain Becker possessed one fibronectin-binding protein, FnbA, and that FnbA was the predominant protein involved in invasion of non-phagocytic HeLa cells. By genetic analysis of strains with different amounts of capsule, we demonstrated that capsule impeded invasion of HeLa cells by masking bacterial cell-wall anchored protein FnbA. Using variants with different levels of mgrA transcription, we further demonstrated that MgrA negatively impacted invasion by activating the cap genes involved in capsule biosynthesis and repressing the fnbA gene. Thus, we conclude that MgrA negatively impacts cell invasion of S. aureus Becker by promoting capsule and repressing FnbA.