Mechanisms by which S. aureus subverts opsonophagocytosis. (A) Coagulase associates with human prothrombin to form enzymatically active staphylothrombin, which in turn cleaves fibrinogen generating fibrin fibrils. The R domain of Coa drives the formation of the bacterial fibrin shield that protects bacteria from phagocytosis. (B) Staphylococcal protein A (SpA) and staphylococcal IgG-binding protein (Sbi) binds Fc domains of IgGs impeding neutrophil-mediated opsonophagocytosis; SpA also inhibits antibody response to infection by binding VH3-type IgM on the surface of B cells; (C) Cytolytic toxins (e.g., α-hemolysin [Hla], leukocidin ED [LukED], and Panton-Valentine leukocidin [PVL]) mediate lysis of immune host cells; LuKED and Hla target neutrophils and macrophages; Hla also lyses monocytes; PVL kills neutrophils and monocytes; (D) Staphylococcal complement inhibitor (SCIN) associates with C3 convertase impairing the production of C3a, C3b, and C5a and interfering with complement activation; (E) Formyl peptide receptor-like 1 inhibitory protein (FLIPr) associates with FCγRIIa blocking neutrophils activation and chemotaxis; (F) Capsule (CP) protects the bacterium from opsonophagocytosis by masking other surface-exposed antigens.