Clostridioides difficile toxin (TcdA/TcdB)

Clostridioides difficile toxins, specifically Toxin A (TcdA) and Toxin B (TcdB), are the primary virulence factors responsible for the pathogenesis of Clostridioides difficile infection (CDI). These large exotoxins are glucosyltransferases that target and inactivate small Rho GTPases (such as Rho, Rac, and Cdc42) within host intestinal epithelial cells (UniProt P16154, P18177). The resulting inactivation leads to the collapse of the actin cytoskeleton, disruption of the intestinal mucosal barrier, and a massive inflammatory response, which clinically manifests as diarrhea and colitis (PubMed: 29535343). Therapeutic intervention often focuses on neutralizing these toxins to prevent cellular damage; for instance, the monoclonal antibody bezlotoxumab binds to TcdB to prevent its interaction with host cells, thereby reducing the incidence of recurrent CDI (NIH: PMC5553310). While TcdA was historically considered the primary enterotoxin, TcdB is now recognized as the more potent driver of systemic and local disease in humans.

Other names

C. diff toxinToxin A (TcdA)Toxin B (TcdB)Clostridial glucosylating toxinEnterotoxin (TcdA)Cytotoxin (TcdB)Clostridioides difficile binary toxin (CDT)

Neutralization of the toxin by binding to its receptor-binding domain or other critical epitopes, thereby preventing the toxin from attaching to host cell receptors, undergoing endocytosis, and translocating its catalytic domain into the cytosol (StatPearls, 2023; FDA Zinplava Label).