TY - JOUR
T1 - FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation
AU - Pietrocola, Giampiero
AU - Schubert, Axel
AU - Visai, Livia
AU - Torti, Mauro
AU - Fitzgerald, J. Ross
AU - Foster, Timothy J.
AU - Reinscheid, Dieter J.
AU - Speziale, Pietro
PY - 2005/2/1
Y1 - 2005/2/1
N2 - The bacterium Streptococcus agalactiae is an etiologic agent in the pathogenesis of endocarditis in humans. FbsA, a fibrinogen-binding protein produced by this pathogen, is considered an important virulence factor. In the present study we provide evidence that S agalactiae clinical isolates bearing FbsA attach to fibri nogen and elicit a fibrinogen-dependent aggregation of platelets. Mutants of S agalactiae lacking the fbsA gene lost the ability to attach to fibrinogen and to aggregate platelets. Plasmid-mediated expression of fbsA restored the capability for fibrinogen binding and platelet aggregation in S agalactiae fbsA mutants, and allowed Lactococcus lactis to interact with fibrinogen and to aggregate human platelets. Moreover, a monoclonal anti-FbsA antibody inhibited bacterial adherence to fibrinogen and S agalactiae-induced platelet aggregation. Platelet aggregation was inhibited by aspirin, prostaglandin E1, the peptide RGDS, and the antibody abciximab, demonstrating the specificity of platelet aggregation by S agalactiae and indicating an involvement of integrin glycoprotein IIb/IIIa in the induction of platelet aggregation. Aggregation was also dependent on anti-FbsA IgG and could be inhibited by an antibody against the platelet FcγRIIA receptor. These findings indicate that FbsA is a crucial factor in S agalactiae-induced platelet aggregation and may therefore play an important role in S agalactiae-induced endocarditis.
AB - The bacterium Streptococcus agalactiae is an etiologic agent in the pathogenesis of endocarditis in humans. FbsA, a fibrinogen-binding protein produced by this pathogen, is considered an important virulence factor. In the present study we provide evidence that S agalactiae clinical isolates bearing FbsA attach to fibri nogen and elicit a fibrinogen-dependent aggregation of platelets. Mutants of S agalactiae lacking the fbsA gene lost the ability to attach to fibrinogen and to aggregate platelets. Plasmid-mediated expression of fbsA restored the capability for fibrinogen binding and platelet aggregation in S agalactiae fbsA mutants, and allowed Lactococcus lactis to interact with fibrinogen and to aggregate human platelets. Moreover, a monoclonal anti-FbsA antibody inhibited bacterial adherence to fibrinogen and S agalactiae-induced platelet aggregation. Platelet aggregation was inhibited by aspirin, prostaglandin E1, the peptide RGDS, and the antibody abciximab, demonstrating the specificity of platelet aggregation by S agalactiae and indicating an involvement of integrin glycoprotein IIb/IIIa in the induction of platelet aggregation. Aggregation was also dependent on anti-FbsA IgG and could be inhibited by an antibody against the platelet FcγRIIA receptor. These findings indicate that FbsA is a crucial factor in S agalactiae-induced platelet aggregation and may therefore play an important role in S agalactiae-induced endocarditis.
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U2 - 10.1182/blood-2004-06-2149
DO - 10.1182/blood-2004-06-2149
M3 - Article
C2 - 15383464
AN - SCOPUS:12844265266
VL - 105
SP - 1052
EP - 1059
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -