Clostridioides difficile toxins A and B (TcdA and TcdB)

Clostridioides difficile toxins A (TcdA) and B (TcdB) are the primary virulence factors produced by the Gram-positive bacterium C. difficile, responsible for the clinical manifestations of Clostridioides difficile infection (CDI) [1]. These large clostridial toxins function as glucosyltransferases that target and inactivate host Rho-family GTPases, such as Rho, Rac, and Cdc42 [2]. This inactivation leads to the collapse of the actin cytoskeleton, disruption of the intestinal epithelial barrier, and the induction of massive inflammatory responses and cell death [3]. TcdA is traditionally characterized as an enterotoxin that increases intestinal permeability, while TcdB is a potent cytotoxin, though both contribute significantly to the pathogenesis of diarrhea and colitis [1, 2]. Therapeutic strategies targeting these toxins include monoclonal antibodies like bezlotoxumab, which binds to TcdB to neutralize its effects and prevent recurrence of infection [4]. Unlike traditional antibiotics that target the bacteria itself, toxin-neutralizing agents aim to mitigate the damage caused by the toxins during the course of the disease [4].

Other names

C. difficile toxinsClostridium difficile toxinsEnterotoxin ACytotoxin BTcdATcdB

Monoclonal antibodies bind to the toxins (specifically TcdB for bezlotoxumab) to neutralize their activity and prevent them from binding to and entering host colonic cells, thereby reducing mucosal damage and inflammation [4].