Plasminogen enhances virulence of group A streptococci by streptokinase-dependent and streptokinase-independent mechanisms

Interactions between host plasminogen (Plg) and streptokinase (SK) secreted by group A streptococci ( GAS) have been hypothesized to promote bacterial invasion of tissues. The virulence of GAS strain UMAA2616, after being subcutaneously inoculated into mice, was studied. Skin lesions and mortality were observed after inoculation of 7 x 10(6) cfu. Coadministration of human Plg with UMAA2616 markedly increased virulence. SK-deficient UMAA2616 (UMAA2616-SK-) was generated. Mean skin-lesion area and mortality, after bacterial inoculation (3 x 10(5) cfu), were significantly greater with UMAA2616 in the presence of human Plg than with UMAA2616-SK- in the presence of human Plg (P = .0001). Human Plg also enhanced UMAA2616-SK- vir ulence. Exogenous human Plg enhanced the virulence of MGAS166, a human clinical isolate. These findings suggest that SK-Plg interactions are an important determinant of GAS invasiveness in vivo and that both SK and host Plg activators appear to promote virulence of GAS by catalyzing plasmin formation.