Clostridioides difficile toxin A combined repetitive oligopeptides domain (TcdA-CROP)

Clostridioides difficile toxin A (TcdA) is a major virulence factor responsible for the clinical manifestations of C. difficile infection (CDI), including diarrhea and colitis [1]. The C-terminal repeat domain, frequently termed the combined repetitive oligopeptides (CROPs) domain, is the region of the toxin responsible for binding to carbohydrate receptors on the surface of host intestinal epithelial cells [2]. This domain consists of multiple repetitive sequences that form a solenoid-like structure, facilitating multivalent binding to glycans such as the Lewis X and Y antigens [3]. Once the CROPs domain anchors the toxin to the cell membrane, the toxin is internalized via receptor-mediated endocytosis, leading to the glucosylation of host Rho GTPases and subsequent cell death [4]. Because this domain is essential for the initial step of toxin entry, it has become a primary target for therapeutic intervention, including neutralizing monoclonal antibodies like actoxumab and various vaccine candidates designed to elicit a protective immune response [5]. [1] UniProt P16154 (TCDA_CLODI). [2] Greco et al. (2006) PMID: 16412602. [3] Voth & Ballard (2005) PMID: 15659137. [4] Jank & Aktories (2013) PMID: 23595305. [5] Gerding et al. (2018) PMID: 29562316.

Other names

TcdA C-terminal repeat domainTcdA receptor-binding domainTcdA-CBDClostridium difficile toxin A C-terminal repeats

Neutralization of toxin binding to host cell surface receptors, thereby preventing toxin internalization and subsequent cellular damage.