Immune evasion proteins from Staphylococcus aureus and therapeutic evaluation of staphylococcal complement-controlling proteins
Complement as a central element of human host innate immunity provides defense against infectious microbes. However, the human pathogen Staphylococcus aureus expresses multiple complement inhibitors including the extracellular fibrinogen-binding protein (Efb). Its complement inhibitory mechanism at the molecular level, however, is still poorly understood. Complement also can be very harmful to the human host when inadequately regulated as demonstrated by the occurrence of complement-mediated diseases. A need for complement control is therefore necessary and in this context, staphylococcal complement inhibitors have a high anti-inflammatory potential. It was therefore the goal of this study to describe the complement inhibitory mechanism of Efb and to examine the protective potential of it in complement-mediated cell damage. Efb acquires the central complement proteins Factor H and C3 to form a tripartite complex. Within the complex, Efb induces a conformational change of C3 which makes it highly susceptible for cleavage by the human serine protease Factor I, making C3 incapable of participating in the complement activation. Efb also binds the human glycoprotein vitronectin representing a novel ligand of Efb. The Efb-vitronectin complex (i) reduces TCC formation and (ii) facilitates adhesion of S. aureus to human alveolar epithelial cells.