MITISCD36LTA

The role of glycoprotein CD36 as a platelet receptor for Streptococci and Staphylococci

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 Obiettivo del progetto (Objective)

'The binding of microorganisms to human platelets is a central process in the pathogenesis of Infective endocarditis. The deletion of genes encoding platelet adhesins in Staphylococcus aureus and Streptococcus mitis, two leading causes of Infective endocarditis, has been shown to result in a reduction in virulence in animal models of infective endocarditis. While investigating the S. mitis virulence factors that are responsible for the adherence of bacterial cells directly to platelets we identified that bacterial lipoteichoic acid interacts with the platelet membrane receptor CD36. CD36 is a recognised mammalian receptor for bacterial lipoteichoic acid but this is the first time it has been identified as a receptor for the adherence of bacteria to platelets. This adherence phenotype appears to be conserved across other gram positive pathogens as we were also able to demonstrate that S. aureus lipoteichoic acid contributes to the direct attachment of S. aureus bacterial cells to platelets.

The purpose of this study is to investigate the molecular interaction of the gram positive pathogens S. mitis and S. aureus and their respective lipoteichoic acids with CD36 and platelets. This will help to identify the role of this interaction in the pathogenesis of infective endocarditis and help define the recognition of bacterial LTA by the immune system.'

Introduzione (Teaser)

Platelets are traditionally known for their anti-bleeding or coagulation activity. European scientists discovered a novel role of platelets in tackling bacterial pathogens.

Descrizione progetto (Article)

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.