The Effects of Cell Envelope Localization of FnBP-A on Staphylococcus aureus FnBP-A Dependent Phenotypes
Abstract
Staphylococcus aureus employs an arsenal of virulence factors for survival and pathogenesis, including the fibronectin binding proteins (FnBPs) which facilitate adhesion, cell invasion, and biofilm formation. Overexpression of FnBP-A in MRSA USA300 has also been shown to cause serum-, FnBP-A-, and growth dependent hyperclumping in vitro. The fnbA gene encodes the topogenic YSIRK motif associated with protein localization to the cross wall of actively growing cells. This study investigated the role of FnBP-A localization on FnBP-A-mediated phenotypes by assessing the impact of swapping the encoded signal peptide of fnbA as a means of mislocalizing the protein. Contrary to the conventional understanding of YSIRK proteins, we did not observe FnBP-A localized within the cross wall. Instead, we showed the YSIRK motif likely promotes enhanced FnBP-A secretion and expression. Understanding the mechanisms influencing virulence factor function, including topogenic motifs, enhances our understanding of S. aureus pathogenesis, informing the development of novel therapeutics.