Streptococcus pyogenes and its interactions with the human host

Abstract: We have found that a set of group A streptococcal strains, primarily associated with skin infections, express surface-associated M proteins that bind plasminogen and plasmin with high affinity. The binding is mediated by a common 13 amino acid internal repeated sequence located in the NH2-terminal surface-exposed portion of these M proteins. It could be demonstrated that plasminogen, absorbed by the bacteria when grown in plasma, could be activated by exogenous and endogenous streptokinase, a potent plasminogen activating protein that is secreted by group A streptococci, thereby providing the bacteria with a surface-associated enzyme that could act on fibrin films or other tissue barriers in the infected host. While only a subset of these bacteria bind plasminogen, almost all group A streptococcal strains bind fibrinogen. It is known that this property is coupled to members of the M protein family. We first identified the fibrinogen-binding region in the type M1 and M5 proteins and then generated an isogenic strain expressing an M5 protein lacking the fibrinogen-binding region. This strain had lost the ability to resist phagocytosis in human blood, a feature that is characteristic for group A streptococci. Furthermore, streptococcal mutants expressing versions of the fibrinogen non-binding M4 protein grafted with the fibrinogen-binding regions from M1 or M5 were generated. The manipulation converted these strains from phagocytosis sensitive to phagocytosis resistant, demonstrating the importance of the fibrinogen-binding capacity for bacterial survival. The ability to bind fibrinogen also gives the bacteria the ability to interact with platelets. Fibrinogen serves as a link between the bacteria and the platelet and the subsequent binding of antibodies directed against the bacteria to the FcgRIIa receptor can induce platelet activation and aggregation, a property that may contribute to acute complications in severe group A streptococcal infection.