Abstract

Bacteria rely on surface-associated proteins for host colonisation and pathogenesis. TIE proteins are highly prevalent and diverse in Gram-positive bacteria, and are known or predicted to play roles in bacterial adhesion to host tissue and biofilm formation. These cell wall-anchored proteins are composed of domains containing self-generating intramolecular thioester, isopeptide and ester cross-links between amino acid sidechains. TIE proteins may have evolved to mediate fast, mechanically persistent binding of bacteria. The distal adhesin domains of TIE proteins contain reactive thioesters and can be likened to “chemical harpoons”, covalently anchoring bacteria to their targets, such as host cell surface proteins. Bacterial-encoded covalent adhesion is a new molecular principle in host:microbe interactions, and an unexploited antimicrobial target. In addition, all three TIE domain types offer exciting opportunities for protein engineering.