Animals, Antibodies, Monoclonal, Bacterial Proteins, Blood Platelets, CHO Cells, Cells, Cultured, Computational Biology, Cricetinae, Cricetulus, Gene Expression Regulation, Bacterial, Humans, Immunoglobulin Fab Fragments, Membrane Proteins, Mutation, Platelet Adhesiveness, Platelet Aggregation Inhibitors, Platelet Glycoprotein GPIIb-IIIa Complex, Streptococcus gordonii
This work was supported by a Wellcome Trust Research Training Fellowship (no. 084979) awarded to H.J.P. and by a Health Board of Ireland grant (no. RP/2006/211) awarded to S.W.K. and H.F.J.
The concept of an infectious agent playing a role in cardiovascular disease is slowly gaining attention. Among several pathogens identified, the oral bacterium Streptococcus gordonii has been implicated as a plausible agent. Platelet adhesion and subsequent aggregation are critical events in the pathogenesis and dissemination of the infective process. Here we describe the identification and characterization of a novel cell wall-anchored surface protein, PadA (397 kDa), of S. gordonii DL1 that binds to the platelet fibrinogen receptor GPIIbIIIa. Wild-type S. gordonii cells induced platelet aggregation and supported platelet adhesion in a GPIIbIIIa-dependent manner. Deletion of the padA gene had no effect on platelet aggregation by S. gordonii but significantly reduced (>75%) platelet adhesion to S. gordonii. Purified N-terminal PadA recombinant polypeptide adhered to platelets. The padA mutant was unaffected in production of other platelet-interactive surface proteins (Hsa, SspA, and SspB), and levels of adherence of the mutant to fetuin or platelet receptor GPIb were unaffected. Wild-type S. gordonii, but not the padA mutant, bound to Chinese hamster ovary cells stably transfected with GPIIbIIIa, and this interaction was ablated by addition of GPIIbIIIa inhibitor Abciximab. These results highlight the growing complexity of interactions between S. gordonii and platelets and demonstrate a new mechanism by which the bacterium could contribute to unwanted thrombosis.
Pharmacy and Pharmaceutical Sciences
Petersen HJ, Keane C, Jenkinson HF, Vickerman MM, Jesionowski A, Waterhouse JC, Cox D, Kerrigan SW. Human platelets recognize a novel surface protein, PadA, on Streptococcus gordonii through a unique interaction involving fibrinogen receptor GPIIbIIIa. Infection and Immunity. 2010;78(1):413-22
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.