Clostridioides difficile toxin B C-terminal repeat domains (TcdB CROPs)

The Clostridioides difficile toxin B C-terminal repeat domains, commonly known as the Combined Repetitive Oligopeptides (CROPs) domain, are essential structural motifs located at the C-terminus of the TcdB exotoxin. This domain functions as a primary receptor-binding region, facilitating the attachment of the toxin to host cell surface receptors, such as chondroitin sulfate proteoglycan 4 (CSPG4) and various carbohydrates, on intestinal epithelial cells (UniProt: P18177). Following binding, the toxin undergoes receptor-mediated endocytosis, eventually leading to the glucosylation of Rho-family GTPases, cytoskeleton collapse, and cell death (PubMed: 27355474). In the context of disease, TcdB is a major virulence factor responsible for the clinical manifestations of Clostridioides difficile infection (CDI), including severe diarrhea and pseudomembranous colitis (NIH: NBK431054). Therapeutically, the CROPs domain is the target of the FDA-approved monoclonal antibody bezlotoxumab, which binds to specific epitopes within the repeats to neutralize the toxin and prevent its entry into cells (PubMed: 28121507). This neutralization strategy is clinically utilized to reduce the risk of CDI recurrence in high-risk populations.

Other names

Clostridium difficile toxin B C-terminal repeat domainsTcdB CROPs domainCombined repetitive oligopeptides domainTcdB receptor-binding domainToxin B C-terminal repeat region

Neutralization of the toxin by binding to the C-terminal repeat domains, thereby preventing the toxin from attaching to and entering host intestinal epithelial cells (PubMed: 28121507).