Document Type

Article

Publication Date

1-7-2007

Keywords

Antibodies, Antigens, CD, Coagulase, Complement System Proteins, Fibrinogen, Humans, Lactococcus lactis, Mutation, Platelet Aggregation, Platelet Glycoprotein GPIIb-IIIa Complex, Receptors, IgG, Staphylococcus aureus

Comments

This article is available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1932920/?tool=pubmed

Abstract

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.

Disciplines

Life Sciences

Citation

Miajlovic H, Loughman A, Brennan M, Cox D, Foster TJ. Both complement- and fibrinogen-dependent mechanisms contribute to platelet aggregation mediated by staphylococcus aureus clumping factor B. Infection and Immunity 2007;75(7):3335-42.

PubMed ID

17438032

DOI Link

10.1128/IAI.01993-06

Included in

Life Sciences Commons

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