Chemically encoded pH-tunable covalent adhesion by a bacterial thioester domain

Abstract

Thioester domains (TEDs) represent a family of bacterial adhesin domains that mediate covalent anchoring to target ligands via an intramolecular thioester bond. Although the broad distribution of TEDs among Gram-positive bacteria suggests a critical functional role, the biological significance of this covalent mechanism remains unclear. In this study, we demonstrated that TED-mediated covalent anchoring is reversible and that its equilibrium is regulated by pH. Specifically, SfbI-TED from Group A Streptococcus binds tightly to fibrinogen at physiological pH, whereas mild acidification to pH 6.0 induces rapid dissociation of the complex. Thermodynamic analyses revealed that this pH-responsiveness arises from the intrinsic properties of the thioester bond within the TED. Similar pH-dependent behavior was observed in phylogenetically distinct TEDs, suggesting that pH-responsive adhesion is a conserved feature of the TED family across Gram-positive bacteria. TeaserA reactive thioester bond in a Gram-positive adhesin acts as a pH sensor to enable environment-responsive adhesion.