Oral streptococci and cardiovascular disease: searching for the platelet aggregation-associated protein gene and mechanisms of Streptococcus sanguis-induced thrombosis

J Periodontol. 2005 Nov;76(11 Suppl):2101-5. doi: 10.1902/jop.2005.76.11-S.2101.


Background: Pathogenic mechanisms in infective endocarditis, disseminated intravascular coagulation, and cardiovascular events involve the aggregation of platelets into thrombi. Attendant infection by oral bacteria contributes to these diseases. We have been studying how certain oral streptococci induce platelet aggregation in vitro and in vivo. Streptococcus sanguis expresses a platelet aggregation-associated protein (PAAP), which contributes little to adhesion to platelets. When specific antibodies or peptides block PAAP, S. sanguis fails to induce platelet aggregation in vitro or in vivo.

Methods: We used subtractive hybridization to identify the gene encoding for PAAP.

Results: After subtraction of strain L50 (platelet aggregation-negative), four strain 133-79 specific sequences were characterized. Sequence agg4 encoded a putative collagen-binding protein (CbpA), which was predicted to contain two PAAP collagen-like octapeptide sequences. S. sanguis CbpA- mutants were constructed and tested for induction of platelet aggregation in vitro. Platelet aggregation was substantially inhibited when compared to the wild-type using platelet-rich plasma from the principal donor, but adhesion was unaffected. Other donor platelets responded normally to the CbpA- strain, suggesting additional mechanisms of response to S. sanguis. In contrast, CshA- and methionine sulfoxide reductase-negative (MsrA-) strains neither adhered nor induced platelet aggregation.

Conclusions: CbpA was suggested to contribute to site 2 interactions in our two-site model of platelet aggregation in response to S. sanguis. Platelet polymorphisms were suggested to contribute to the thrombogenic potential of S. sanguis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Antigens, Bacterial / genetics*
  • Bacterial Proteins / genetics*
  • Cardiovascular Diseases / microbiology*
  • Endocarditis, Bacterial / microbiology
  • Genes, Bacterial
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Platelet Adhesiveness / genetics
  • Platelet Aggregation / genetics
  • Polymorphism, Genetic
  • Streptococcus sanguis / genetics*
  • Streptococcus sanguis / pathogenicity*
  • Thrombosis / microbiology*


  • Antigens, Bacterial
  • Bacterial Proteins
  • CbpA protein, bacteria
  • platelet aggregation-associated protein, Streptococcus