Clostridioides difficile toxin B glucosyltransferase domain (TcdB-GTD)

The Clostridioides difficile toxin B glucosyltransferase domain (TcdB-GTD) is the N-terminal catalytic component of Toxin B, a major virulence factor produced by the bacterium Clostridioides difficile (UniProt: P18177). This domain acts as the toxin's effector by entering the host cell cytosol and enzymatically transferring a glucose moiety from UDP-glucose to conserved residues on Rho-family GTPases, such as RhoA, Rac1, and Cdc42 (PubMed: 22431647). This covalent modification irreversibly inactivates these molecular switches, leading to the rapid collapse of the actin cytoskeleton, loss of intestinal epithelial barrier integrity, and the induction of pro-inflammatory signaling and apoptosis (PubMed: 29305546). These cellular changes manifest clinically as the severe diarrhea and inflammation associated with pseudomembranous colitis. As the primary engine of TcdB-mediated toxicity, the GTD is a high-priority target for therapeutic development, including small-molecule inhibitors and neutralizing antibodies (PubMed: 25223279). While the FDA-approved antibody Bezlotoxumab targets the C-terminal binding domain of Toxin B, research continues into GTD-specific inhibitors to directly block the enzymatic activity responsible for host tissue damage (PubMed: 30104356).

Other names

TcdB effector domainGlucosyltransferase domain of Toxin BTcdB N-terminal catalytic domainC. difficile Toxin B GTD

Neutralization of the toxin to prevent cellular entry or direct inhibition of the enzymatic transfer of glucose to host Rho GTPases to maintain cytoskeletal integrity.