TIE proteins & covalent adhesion of Gram-positive bacteria

Commensal and pathogenic bacteria rely on surface-associated adhesins for colonization, pathogenesis, and persistence within host tissues. Until recently, adhesins were known only to interact with host targets through non-covalent interactions. We have identified a large class of surface proteins composed of domains containing intramolecular cross-links between amino acid side-chains. These TIE (thioester, isopeptide, ester) proteins are exceedingly prevalent and diverse in Gram-positive bacteria, and can be likened to “chemical harpoons”, covalently anchoring bacteria to their targets on host cell surfaces. TIE proteins may therefore have evolved to mediate fast, mechanically persistent binding of bacteria to host tissues. Insights yielded by the combined efforts of structural and cell biology support covalent bacteria-host binding as a new molecular principle in host-microbe interaction, and represents an unexploited target to treat bacterial infection.