Extracellular fibrinogen binding protein, Efb, from Staphylococcus aureus binds to platelets and inhibits platelet aggregation.
S. aureus produces and secretes a protein, extracellular fibrinogen binding protein (Efb), which contributes to virulence in wound infection. We have shown here that Efb is a potent inhibitor of platelet aggregation. Efb can bind specifically to platelets by two mechanisms; 1) to fibrinogen naturally bound to the surface of activated platelets and 2) also directly to a surface localized component on the platelets. This latter binding of Efb is independent of fibrinogen. The specific binding of Efb to the putative 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 activated platelets could be blocked by a monoclonal antibody against this integrin, whereas the Efb-mediated fibrinogen binding could not be blocked. The enhanced Efb-dependent fibrinogen binding to platelets is of a nature that does not promote aggregation of the platelets; instead it inhibits aggregation. The anti-thrombotic action of Efb may explain the effect of Efb on wound healing, which is delayed in the presence of Efb.
Shannon
Oonagh
O
Division of Clinical bacteriology, Department of Laboratory Medicine, Huddinge University Hospital F82, Karolinska Institute, S-141 86 Stockholm, Sweden.
Flock
Jan-Ingmar
JI
D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005978:Glutathione; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000472:pathogenicity
D001426:Bacterial Proteins; C114014:Efb protein, Staphylococcus aureus; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D005340:Fibrinogen; D005978:Glutathione