Covalent host targeting by thioester domains of Gram-positive pathogens

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We have identified a family of protein domains, containing internal thioester bonds, in many surface proteins of some of the most important Gram-positive human pathogens. Internal thioesters have previously only been found in complement proteins where they form covalent bonds to the surface of pathogens. The discovery of reactive thioester bonds in bacterial surface proteins known or predicted to mediate bacterial adhesion suggests the exciting possibility of a previously unrecognised principle in host-bacteria interactions, namely the covalent attachment of bacteria to host tissue.

We aim to study the role of protein domains that contain internal thioesters in bacterial adhesion using a range of in vitro and in vivo experiments including structural biology, protein/protein interactions, chemistry and cell-adhesion.

Given the urgent need to develop new antimicrobial strategies to prevent the looming antibiotics crisis, the discovery of a novel molecular virulence mechanism is an exciting development and needs to be addressed now in a concerted effort bringing together molecular and microbiological expertise as we propose.

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