Pathogen activators of plasminogen

Summary Group A streptococci ( GAS ) express soluble and surface‐bound virulence factors. Secreted streptokinase ( SK ) allelic variants exhibit varying abilities to activate host plasminogen ( P g), and GAS pathogenicity is associated with P g activation and localization of the resulting plasmin ( P m) on the bacterial surface to promote dissemination. The various mechanisms by which GAS usurp the host proteolytic system are discussed, including the molecular sexuality mechanism of conformational activation of the P g zymogen ( P g*) and subsequent proteolytic activation of substrate P g by the S•KPg* and SK•Pm catalytic complexes. Substantial progress has been made to delineate both processes in a unified mechanism. Pm coats the bacteria by direct and indirect binding pathways involving plasminogen‐binding group A streptococcal M‐like (PAM) protein and host fibrin(ogen). Transgenic mouse models using human P g are being optimized to mimic infections by SK variants in humans and to define in vivo combined mechanisms of these variants and PAM .