Clostridioides difficile toxin A and Clostridioides difficile toxin B (TcdA and TcdB)

Clostridioides difficile toxin A (TcdA) and toxin B (TcdB) are the two principal exotoxins and virulence factors produced by C. difficile, a Gram-positive anaerobe responsible for antibiotic-associated diarrhea and colitis. Both toxins belong to the large clostridial toxin (LCT) family and share a similar multi-domain organization: an N-terminal glucosyltransferase domain (GTD) that catalyzes the glucosylation and inactivation of Rho family small GTPases, a cysteine protease domain (CPD) that mediates autocleavage and release of GTD within host cells, a central delivery and receptor-binding (DRBD) domain that facilitates endocytosis and pore formation, and a C-terminal combined repetitive oligopeptide (CROPs) domain that is critical for receptor binding on the host cell surface. The action of TcdA and TcdB ultimately leads to disassembly of the actin cytoskeleton, cell rounding, loss of tight junctions, cell death, and strong inflammatory responses triggering the clinical symptoms of C. difficile infection[3][4][5][1][2]. Because of their essential role in disease, both toxins are major targets of diagnostic tests and therapeutic antibodies, such as bezlotoxumab, that neutralize toxin activity and reduce recurrence risk.

Other names

Toxin A (TcdA)Toxin B (TcdB)Large clostridial toxins (LCTs)

Neutralization of toxin function (e.g., monoclonal antibodies bind toxin domains, blocking cell receptor binding and downstream pathogenicity) - Inhibition of cell binding/entry (prevention of receptor-mediated endocytosis) - Blockade of enzymatic glucosyltransferase activity (some experimental approaches)