Clostridioides difficile Toxin B glucosyltransferase domain (TcdB-GTD) (TcdB-GTD)

The Clostridioides difficile Toxin B glucosyltransferase domain (TcdB-GTD) is the N-terminal catalytic effector of the TcdB exotoxin, a primary virulence factor in Clostridioides difficile infections [1]. Following the holotoxin's entry into host cells via endocytosis, the GTD is translocated into the cytosol and released through autoproteolytic cleavage [2]. Once in the cytoplasm, the GTD functions as a glycosyltransferase that catalyzes the transfer of glucose from UDP-glucose to host Rho-family GTPases, such as RhoA, Rac1, and Cdc42 [3]. This covalent modification inactivates the GTPases, leading to the collapse of the actin cytoskeleton, loss of intestinal epithelial barrier integrity, and induction of cell death [4]. Clinically, this damage results in the severe diarrhea and inflammation characteristic of pseudomembranous colitis [4]. Because the GTD is the domain directly responsible for intracellular toxicity, it is a major target for therapeutic development, including small-molecule inhibitors and neutralizing antibodies aimed at blocking its enzymatic activity or preventing its release into the cytosol [5]. Sources: [1] UniProt P18177 (TcdB_CLODI) [2] PubMed: 20435015 [3] PubMed: 7753767 [4] PubMed: 28165481 [5] PubMed: 25616760

Other names

TcdB-GTDGlucosyltransferase domain of Toxin BTcdB1-543GTD

Neutralization of toxin binding and entry (Bezlotoxumab); Inhibition of autoproteolytic release of the glucosyltransferase domain (Ebselen); Competitive or non-competitive inhibition of the glucosyltransferase enzymatic activity (Experimental inhibitors).