FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation.
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 fibrinogen 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 E(1,) 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 FcgammaRIIA 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.
Pietrocola
Giampiero
G
University of Pavia, Department of Biochemistry, Viale Taramelli 3/B 27100 Pavia, Italy.
Schubert
Axel
A
Visai
Livia
L
Torti
Mauro
M
Fitzgerald
J Ross
JR
Foster
Timothy J
TJ
Reinscheid
Dieter J
DJ
Speziale
Pietro
P
D001426:Bacterial Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D010957:Plasmids; D010974:Platelet Aggregation / Q000187:drug effects*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000254:growth & development
D001426:Bacterial Proteins; D002352:Carrier Proteins; C499709:FbsA protein, Streptococcus agalactiae; D011994:Recombinant Proteins; D005340:Fibrinogen; D002118:Calcium