Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the Paf receptor

Waller, A. K., Sage, T., Kumar, C., Carr, T., Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352 and Clarke, S. R. (2013) Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the Paf receptor. Journal of Infectious Diseases, 208 (12). pp. 2046-2057. ISSN 1537-6613 doi: 10.1093/infdis/jit398

Abstract/Summary

Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S.aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and S. aureus and reduced platelet thrombus formation in vitro. The presence of D-alanine on LTA is necessary for the full inhibitory effect. Inhibition of aggregation was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody and Ginkgolide B, a well-defined PafR antagonist, demonstrating that the LTA inhibitory signal occurs via PafR. Using a cyclic AMP (cAMP) assay and a western blot for phosphorylated VASP, we determined that cAMP levels increase upon platelet incubation with LTA, an effect which inhibits platelet activation. This was blocked when platelets were preincubated with Ginkgolide B. Furthermore, LTA reduced haemostasis in a mouse tail-bleed assay.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/33466
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Oxford University Press
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