title: Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the Paf receptor.
abstract: 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 hemostasis in a mouse tail-bleed assay.
authors.affiliation: School of Biological Sciences.
authors.forename: Amie K
authors.initials: AK
authors.lastname: Waller
authors.forename: Tanya
authors.initials: T
authors.lastname: Sage
authors.forename: Christopher
authors.initials: C
authors.lastname: Kumar
authors.forename: Thomas
authors.initials: T
authors.lastname: Carr
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gibbins
authors.forename: Simon R
authors.initials: SR
authors.lastname: Clarke
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D046934:Ginkgolides / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000502:physiology; D013682:Teichoic Acids / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000378:metabolism* / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D046934:Ginkgolides; D007783:Lactones; D008070:Lipopolysaccharides; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D013682:Teichoic Acids; C039351:platelet activating factor receptor; C009900:lipoteichoic acid; C045856:ginkgolide B; D000242:Cyclic AMP; D002118:Calcium
keywords: Staphylococcus aureus; lipoteichoic acid; platelets
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