FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation

Blood. 2005 Feb 1;105(3):1052-9. doi: 10.1182/blood-2004-06-2149. Epub 2004 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / pharmacology*
  • Bacterial Proteins / physiology*
  • Calcium / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • Cytosol / metabolism
  • Fibrinogen / metabolism
  • Gene Expression
  • Humans
  • Plasmids
  • Platelet Aggregation / drug effects*
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Streptococcus agalactiae / genetics*
  • Streptococcus agalactiae / growth & development

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • FbsA protein, Streptococcus agalactiae
  • Recombinant Proteins
  • Fibrinogen
  • Calcium