Functions of cell surface-anchored antigen I/II family and Hsa polypeptides in interactions of Streptococcus gordonii with host receptors.

Streptococcus gordonii colonizes multiple sites within the human oral cavity. This colonization depends upon the initial interactions of streptococcal adhesins with host receptors. The adhesins that bind salivary agglutinin glycoprotein (gp340) and human cell surface receptors include the antigen I/II (AgI/II) family polypeptides SspA and SspB and a sialic acid-binding surface protein designated Hsa or GspB. In this study we determined the relative functions of the AgI/II polypeptides and Hsa in interactions of S. gordonii DL1 (Challis) with host receptors. For an isogenic mutant with the sspA and sspB genes deleted the levels of adhesion to surface-immobilized gp340 were reduced 40%, while deletion of the hsa gene alone resulted in >80% inhibition of bacterial cell adhesion to gp340. Adhesion of S. gordonii DL1 cells to gp340 was sialidase sensitive, verifying that Hsa has a major role in mediating sialic acid-specific adhesion to gp340. Conversely, aggregation of S. gordonii cells by fluid-phase gp340 was not affected by deletion of hsa but was eliminated by deletion of the sspA and sspB genes. Deletion of the AgI/II polypeptide genes had no measurable effect on hsa mRNA levels or Hsa surface protein expression, and deletion of hsa did not affect AgI/II polypeptide expression. Further analysis of mutant phenotypes showed that the Hsa and AgI/II proteins mediated adhesion of S. gordonii DL1 to human HEp-2 epithelial cells. Hsa was also a principal streptococcal cell surface component promoting adhesion of human platelets to immobilized streptococci, but Hsa and AgI/II polypeptides acted in concert in mediating streptococcal cell-platelet aggregation. The results suggest that Hsa directs primary adhesion events for S. gordonii DL1 (Challis) with immobilized gp340, epithelial cells, and platelets. AgI/II polypeptides direct gp340-mediated aggregation, facilitate multimodal interactions necessary for platelet aggregation, and modulate S. gordonii-host engagements into biologically productive phenomena.

Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce platelet aggregation.

BACKGROUND & AIMS: Clinical studies have suggested an association between cardiovascular disease and infection with Helicobacter pylori. We examined the effect of H. pylori on platelets and the mechanism of the interaction. METHODS: Three of 5 strains of H. pylori induced platelet aggregation with a lag time of 5 +/- 2 minutes that was independent of the toxigenic genes cagA and vacA. Aggregation was inhibited completely by aspirin and a glycoprotein (GP) IIb/IIIa antagonist. Aggregation also was inhibited by monoclonal antibodies that prevented the von Willebrand factor (vWF) interaction with GPIb. vWF-coated H. pylori bound to cells transfected with GPIbalpha but not to mock transfected cells and this was inhibited by an antibody to GPIb. RESULTS: The interaction with platelets appeared to be mediated by vWF because platelet aggregation was blocked by an antibody to vWF. Moreover, a strain of H. pylori that induced platelet aggregation bound vWF to a greater extent than a nonaggregating strain. Aggregation also required IgG and could be inhibited by an antibody to the platelet IgG receptor (FcgammaRIIA). CONCLUSIONS: Some strains of H. pylori induce platelet activation mediated by H. pylori-bound vWF interacting with GPIb, and supported by IgG. These platelet-H. pylori interactions may contribute to the pathogenesis of H. pylori-associated peptic ulcer disease and to the association between H. pylori infection and cardiovascular disease, whereas local platelet effects may contribute to the pathogenesis of H. pylori-associated peptic ulcer disease.