Platelets — role in antimicrobial defence
Platelets are derivatives of megakaryocytes, they are produced in the bone marrow and enter the bloodstream to reach the site of bleeding and induce haemostasis. Accumulating evidence indicates that platelets are implicated in the pathogenesis of infective endocarditis, caused by Staphylococcus aureus and Streptococcus mitis. While investigating the S. mitis virulence factors that are responsible for the binding of bacterial cells to platelets, scientists on the EU-funded 'The role of glycoprotein CD36 as a platelet receptor for Streptococci and Staphylococci' (MITISCD36LTA) project discovered the involvement of platelet membrane receptor CD36. The receptor interacted with the bacterial lipoteichoic acid (LTA) by a so far unknown mechanism that seemed to be conserved across other gram positive pathogens. The key objective of the MITISCD36LTA study was to investigate the molecular mechanism underlying this interaction, by analysing the components that participate in the binding. Researchers identified the region of CD36 where the S.aureus and S.mitis LTA bind, as well as the charged part of LTA implicated in the interaction. Mutations in the CD36 LTA-attachment region abrogated bacterial binding, clearly indicating the importance of this site for the attachment of bacterial pathogens to platelets. Taken together, the delineation of the CD36-bacterial LTA interaction could be exploited therapeutically for the treatment of gram positive bacterial infections. Such treatment could be used to prevent colonisation of human mucosal surfaces with opportunistic pathogens that are difficult to treat with antibiotics. Future work focuses on the investigation of bacterial glycolipid binding with receptors on platelets and macrophages, and their role in platelet activation. This work could unravel a novel role of transient bacteremias, caused by dental caries, on the promotion of atherosclerosis.
Keywords
Platelets, endocarditis, Streptococcus mitis, CD36, bacterial lipoteichoic acid
