Analysis of plasminogen-binding M proteins of Streptococcus pyogenes

Group A streptococci are common human pathogens that cause a variety of inf ections. They express M proteins which are important cell wall-bound type-s pecific virulence factors. We have found that a set of strains, associated primarily with skin infections, express M proteins that bind plasminogen an d plasmin with high affinity. The binding is mediated by a 13-amino-acid in ternal repeated sequence located in the N-terminal surface-exposed portion of these M proteins. This sequence binds to kringle 2 in plasminogen, a dom ain that is not involved in the interaction with streptokinase, a potent gr oup A streptococcal activator of plasminogen. It could be demonstrated that plasminogen, absorbed from plasma by growing group A streptococci expressi ng the plasminogen-binding M proteins, could be activated by exogenous and endogenous streptokinase, thereby providing the bacteria with a surface-ass ociated enzyme that could act on the tissue barriers In the infected host. (C) 2000 Academic Press.