Fig. 1.

Examples demonstrating the evolved ability of S. pyogenes to promote disease in immunocompetent individuals. (A) The surface M protein recruits human C4BP to inhibit complement opsonization (C3b) of the bacterial surface. (B) Secreted streptokinase (SK) binds to human Plg, which causes a conformational change of Plg into a plasmin (Pl) active state. (C) The secreted endoglycosidase EndoS inactivates effector functions of IgG by cleaving off N-glycans from the Fc-region. (D) Secreted superantigen (SAg) causes antigen-independent T cell activation by cross-linking the TCR with HLA-II on antigen presenting cells (APC). SAgs have different affinity for different fully functional HLA-II haplotypes. (E) The STING responds to S. pyogenes-derived c-di-AMP to induce transcription of the interferon β gene, which is inhibited by the enzymatic activity of bacterial NADase. Human STING and S. pyogenes NADase exhibit polymorphisms affecting their relative ability to respond to c-di-AMP and to suppress interferon transcription, respectively.