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

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 indicated that this pH responsiveness is largely dictated by the intrinsic pH sensitivity of the thioester-mediated acyl transfer reaction conserved within TEDs, rather than by surface residues specific to individual TEDs. Similar pH-dependent behavior was observed in phylogenetically distinct TEDs, suggesting that pH-responsive adhesion is likely to be a broadly shared feature of TED-containing adhesins across Gram-positive bacteria.