Human Platelets Recognize a Novel Surface Protein, PadA, on Streptococcus gordonii through a Unique Interaction Involving Fibrinogen Receptor GPIIbIIIa
| Autor: | Janet C. Waterhouse, Howard F. Jenkinson, Steven W. Kerrigan, A. M. Jesionowski, Helen J. Petersen, M. Margaret Vickerman, C Keane, Dermot Cox |
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| Rok vydání: | 2010 |
| Předmět: |
Blood Platelets
Fibrinogen receptor Abciximab Immunology CHO Cells Platelet Glycoprotein GPIIb-IIIa Complex Microbiology Immunoglobulin Fab Fragments Cricetulus Platelet Adhesiveness stomatognathic system Bacterial Proteins Cricetinae Platelet adhesiveness Animals Humans Platelet Cells Cultured Cellular Microbiology: Pathogen-Host Cell Molecular Interactions biology Chinese hamster ovary cell Streptococcus gordonii Antibodies Monoclonal Computational Biology Membrane Proteins Gene Expression Regulation Bacterial Transfection biology.organism_classification Infectious Diseases Mutation Platelet aggregation inhibitor Parasitology Platelet Aggregation Inhibitors |
| Zdroj: | Infection and Immunity. 78:413-422 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00664-09 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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