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Both complement- and fibrinogen-dependent mechanisms contribute to platelet aggregation mediated by Staphylococcus
Helen Miajlovic1, Anthony Loughman, Marian Brennan
1Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
Infection and Immunity
|April 18, 2007
Summary
Staphylococcus aureus ClfB protein aggregates platelets via a fibrinogen-dependent pathway, but a mutant lacking fibrinogen binding can still aggregate platelets through complement activation and antibodies.
Area of Science:
- Microbiology
- Immunology
- Hematology
Background:
- Staphylococcus aureus infection, particularly infective endocarditis, involves platelet activation and aggregation.
- Clumping factor A (ClfA) and fibronectin-binding proteins (FnBPA, FnBPB) are known potent platelet aggregators, acting via fibrinogen or fibronectin-dependent mechanisms requiring specific antibodies.
- Clumping factor B (ClfB) also aggregates platelets, but with a longer lag time, suggesting different mechanisms.
Purpose of the Study:
- To investigate the mechanisms by which Staphylococcus aureus ClfB induces platelet aggregation, specifically examining fibrinogen- and complement-dependent pathways.
- To characterize the role of fibrinogen binding in ClfB-mediated platelet aggregation.
- To determine the necessity of specific antibodies for ClfB-induced platelet aggregation.
Main Methods:
- Construction and use of a non-fibrinogen-binding mutant of ClfB (ClfB Q235A) expressed in Lactococcus lactis.
- Platelet aggregation assays using platelet-rich plasma and gel-filtered platelets.
- Investigation of the roles of fibrinogen, complement, and specific anti-ClfB antibodies in aggregation.
Main Results:
- Wild-type ClfB mediates platelet aggregation in a fibrinogen-dependent manner requiring specific anti-ClfB antibodies.
- The non-fibrinogen-binding ClfB Q235A mutant was unable to aggregate platelets under fibrinogen-dependent conditions.
- However, ClfB Q235A induced platelet aggregation via a complement-dependent pathway that also required specific anti-ClfB antibodies.
Conclusions:
- Staphylococcus aureus ClfB primarily induces platelet aggregation through a fibrinogen-dependent mechanism.
- ClfB can also mediate platelet aggregation via complement activation when fibrinogen binding is absent, provided specific antibodies are present.
- These findings elucidate the distinct pathways of platelet aggregation mediated by different Staphylococcus aureus surface proteins, relevant to understanding infective endocarditis pathogenesis.
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