Clostridioides difficile toxins A and B and their enterocyte receptors (TcdA/TcdB and receptors)

Clostridioides difficile toxins A (TcdA) and B (TcdB) are the primary virulence factors responsible for the pathogenesis of C. difficile infection (CDI) (Aktories et al., 2017). These large clostridial toxins target the colonic epithelium by binding to specific host cell surface receptors, including Frizzled proteins (FZD1, 2, 7) and Chondroitin sulfate proteoglycan 4 (CSPG4) for TcdB, and sucrase-isomaltase or glycoprotein 2 for TcdA (Tao et al., 2016; Yuan et al., 2015; Pothoulakis et al., 1996). Upon binding, the toxins are internalized via receptor-mediated endocytosis, where they subsequently glucosylate and inactivate host Rho GTPases such as Rho, Rac, and Cdc42. This molecular disruption leads to the collapse of the actin cytoskeleton, loss of tight junction integrity, massive fluid secretion, and an intense inflammatory response, manifesting clinically as diarrhea and pseudomembranous colitis (Aktories et al., 2017). Therapeutic strategies include the use of monoclonal antibodies like Bezlotoxumab, which binds to TcdB and prevents its interaction with host receptors, thereby reducing the risk of recurrent infection (Wilcox et al., 2017). Understanding the toxin-receptor interface is critical for developing next-generation antitoxins and vaccines to combat antibiotic-resistant strains.

Other names

TcdATcdBEnterotoxin ACytotoxin BFrizzled receptorsCSPG4Sucrase-isomaltaseGP2

Neutralization of toxins to prevent binding and internalization into host enterocytes