IAI Accepts, published online ahead of print on 2 November 2009

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Infect. Immun. doi:10.1128/IAI.00664-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Human platelets recognize a novel surface protein PadA on Streptococcus gordonii through a unique interaction involving fibrinogen receptor GPIIbIIIa

Helen J. Petersen, Ciara Keane, Howard F. Jenkinson^*, M. Margaret Vickerman, Amy Jesionowski, Janet C. Waterhouse, Dermot Cox, and Steven W. Kerrigan

Department of Oral and Dental Science, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, United Kingdom; Molecular and Cellular Therapeutics, School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Eire; Department of Oral Biology, State University of New York, Foster Hall, Buffalo, New York 14214-3092, USA

^* To whom correspondence should be addressed. Email: howard.jenkinson{at}bristol.ac.uk.

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 adherence levels 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.