Simplified model of how GAS hijacks the host fibrinolytic system to facilitate invasion. A) At the site of GAS infection, rigorous procoagulant and inflammatory response will be initiated to release cytokines and activate coagulation system. Local thrombosis and microvascular occlusion will wall off bacteria from systemic spread. An example is given as to how a GAS virulence factor, M protein, can activate the intrinsic pathway of coagulation and also release a potent inflammation stimulant bradykinin to promote a host response. B) GAS produces the plasminogen activator streptokinase (SK) to form a SK/plasminogen complex, which will activate circulating plasminogen to plasmin. The SK/plasminogen complex is resistant to host fibrinolysis inhibitors such as α2-antiplasmin. Additionally, GAS also recruits the fibrinogen/SK/plasminogen complex by binding fibrinogen through M or M-related proteins or binding plasminogen/plasmin directly through plasminogen receptors. As a result, the bacteria are able to overcome local thrombosis to spread systemically.