Abstract
The surface of Staphylococcus aureus is decorated with over 20 proteins that are covalently anchored to peptidoglycan by the action of sortase A. These cell wall-anchored (CWA) proteins can be classified into several structural and functional groups. The largest is the MSCRAMM family, which is characterized by tandemly repeated IgG-like folded domains that bind peptide ligands by the dock lock latch mechanism or the collagen triple helix by the collagen hug. Several CWA proteins comprise modules that have different functions, and some individual domains can bind different ligands, sometimes by different mechanisms. For example, the N-terminus of the fibronectin binding proteins comprises an MSCRAMM domain which binds several ligands, while the C-terminus is composed of tandem fibronectin binding repeats. Surface proteins promote adhesion to host cells and tissue, including components of the extracellular matrix, contribute to biofilm formation by stimulating attachment to the host or indwelling medical devices followed by cell-cell accumulation via homophilic interactions between proteins on neighboring cells, help bacteria evade host innate immune responses, participate in iron acquisition from host hemoglobin, and trigger invasion of bacteria into cells that are not normally phagocytic. The study of genetically manipulated strains using animal infection models has shown that many CWA proteins contribute to pathogenesis. Fragments of CWA proteins have the potential to be used in multicomponent vaccines to prevent S. aureus infections.