This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01993-06v1 75/7/3335    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miajlovic, H. Articles by Foster, T. J. Search for Related Content PubMed PubMed Citation Articles by Miajlovic, H. Articles by Foster, T. J.

Both Complement- and Fibrinogen-Dependent Mechanisms Contribute to Platelet Aggregation Mediated by Staphylococcus aureus Clumping Factor B

Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland,¹ Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin 2, Ireland²

Received 20 December 2006/ Returned for modification 4 February 2007/ Accepted 5 April 2007

Staphylococcus aureus can stimulate activation and aggregation of platelets, which are thought to be factors in the development of infective endocarditis. Previous studies have identified clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as potent platelet aggregators. These proteins are able to stimulate rapid platelet aggregation by either a fibrinogen- or a fibronectin-dependent process which also requires antibodies specific to each protein. Slower aggregation has been seen in other systems where specific fibrinogen binding ligands are absent and platelet aggregation is mediated by complement and specific antibodies. Bacteria expressing ClfB aggregate platelets with a longer lag time than ClfA or FnBPA and FnBPB. In order to investigate whether ClfB causes platelet aggregation in a complement- or fibrinogen-dependent manner, a non-fibrinogen-binding mutant of ClfB (ClfB Q235A) was constructed. Lactococcus lactis expressing ClfB Q235A was able to stimulate platelet aggregation in platelet-rich plasma without a significant increase in lag time. The requirements for platelet aggregation were investigated using gel-filtered platelets. Fibrinogen and specific anti-ClfB antibodies were found to be sufficient to allow platelet aggregation mediated by the wild-type ClfB protein. It seems that ClfB causes platelet aggregation by a fibrinogen-dependent mechanism. The non-fibrinogen-binding ClfB mutant was unable to stimulate platelet aggregation under these conditions. However, bacteria expressing ClfB Q235A caused platelet aggregation in a complement-dependent manner which required specific anti-ClfB antibodies.

Published ahead of print on 16 April 2007.

Editor: A. Camilli

This article has been cited by other articles:

• Walsh, E. J., Miajlovic, H., Gorkun, O. V., Foster, T. J. (2008). Identification of the Staphylococcus aureus MSCRAMM clumping factor B (ClfB) binding site in the {alpha}C-domain of human fibrinogen. Microbiology 154: 550-558 [Abstract] [Full Text]