Summary

S. aureus produces and secretes a protein, extracellular fibrinogenbinding protein (Efb), which contributes to virulence inwound infection.We have shown here that Efb is a potent inhibitorof platelet aggregation. Efb can bind specifically to plateletsby two mechanisms; 1) to fibrinogen naturally bound to the surfaceof activated platelets and 2) also directly to a surface localizedcomponent on the platelets. This latter binding of Efb isindependent of fibrinogen. The specific binding of Efb to theputative receptor on the platelet surface results in a stimulated,non-functional binding of fibrinogen in a dose dependent manner, distinct from natural binding of fibrinogen to platelets.The natural binding of fibrinogen to GPIIb/IIIa on activatedplatelets could be blocked by a monoclonal antibody againstthis integrin, whereas the Efb-mediated fibrinogen binding couldnot be blocked.The enhanced Efb-dependent fibrinogen bindingto platelets is of a nature that does not promote aggregation ofthe platelets; instead it inhibits aggregation.The anti-thromboticaction of Efb may explain the effect of Efb on wound healing,which is delayed in the presence of Efb.