Extracellular fibrinogen-binding protein, Efb, from Staphylococcus aureus blocks platelet aggregation due to its binding to the alpha-chain

• Published in: The Journal of biological chemistry 2001-08, Vol.276 (34), p.31691-31697
• Main Authors: Palma, M, Shannon, O, Quezada, H C, Berg, A, Flock, J I
• Format: Article
• Language: English
• Subjects: Bacterial Proteins; Base Sequence; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Carrier Proteins - physiology; Chromatography, Affinity; Coagulase - metabolism; DNA Primers; Efb protein; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; fibrinogen-binding protein; Humans; Platelet Aggregation - physiology; Protein Binding; Staphylococcus aureus; Staphylococcus aureus - metabolism
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M104554200

Extracellular fibrinogen-binding protein (Efb) secreted by Staphylococcus aureus has previously been shown to contribute to pathogenesis in a rat wound infection model. Also antibodies against Efb exhibited a protective effect in a mouse mastitis model. The interaction between Efb and fibrinogen is divalent, with one binding site within the N-terminal repeat region in Efb and one at the C terminus. In this study we show that the distal D domain of fibrinogen contains at least one of the binding domains recognized by Efb. Efb stimulates fibrinogen binding to ADP-activated platelets. Furthermore, Efb inhibits ADP-induced, fibrinogen-dependent platelet aggregation in a concentration-dependent manner. This implies that Efb modifies platelet function by amplifying a non-functional interaction between fibrinogen and platelets. Efb recognizes the A alpha-chain of the D fragment of fibrinogen. The RGD sequence on the A alpha-chain is located close to the region recognized by Efb and contains a putative binding site for the platelet integrin GPIIb/IIIa receptor complex involved in platelet aggregation.