Extracellular fibrinogen-binding protein, Efb, from Staphylococcus aureus blocks platelet aggregation due to its binding to the alpha-chain.
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.
Palma
M
M
Department of, Microbiology, Pathology, and Immunology, F82, Huddinge University Hospital, Karolinska Institutet, S-14186 Stockholm, Sweden.
Shannon
O
O
Quezada
H C
HC
Berg
A
A
Flock
J I
JI
D001426:Bacterial Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D002846:Chromatography, Affinity; D003030:Coagulase / Q000378:metabolism; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010974:Platelet Aggregation / Q000502:physiology*; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000378:metabolism*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D003030:Coagulase; D017931:DNA Primers; C114014:Efb protein, Staphylococcus aureus