Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558772
Title: Modulation of platelet activity by Staphylococcus aureus teichoic acids
Author: Waller, Amie K.
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2012
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Abstract:
S. aureus is a major human pathogen that causes a wide variety of diseases. Although interaction with platelets of surface bound proteins has been well studied, relatively little is known concerning the actions of molecules released into the extracellular milieu by S. aureus. In this study molecules from the supernatant of S. aureus were extracted and tested for their ability to cause or inhibit aggregation of platelets. An inhibitory molecule was discovered, that was found to be resistant to heat treatment and lysostaphin incubation and not to be controlled by the agr system or sar A. This molecule was identified as lipoteichoic acid (L TA), a repeating structure bound to the cell membrane in S. aureus which is released into the extracellular milieu at relatively high concentrations. The structure of L TA was found to be important for full inhibition as a dltABCD mutant caused less inhibition than wild type. L TA from B. subtilis was also found to inhibit platelet aggregation. L TA caused inhibition by increasing cAMP levels, thus inhibiting calcium flux, via a G-protein coupled receptor on the surface of platelets, platelet activating factor receptor. L TA also inhibited the formation of thrombi under flow and caused an increase in bleeding time in a mouse model of haemostasis. Due to some structural similarity to LTA, wall teichoic acid (WTA) was also tested for its effect upon platelets and though unable to cause direct activation or inhibition, it did cause an increase in aggregation when other agonists were used. This was found to be independent of complement and IgG and may potentially occur via a scavenger receptor. These data here presented give a greater understanding of the many interactions that occur between S. aureus and platelets during infection and additionally suggest a theory for the often observed delay in inhibition of wound healing. 4.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.558772  DOI: Not available
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