Clostridioides difficile toxin receptors

The intestinal epithelial brush border receptors for Clostridioides difficile toxins are a group of host cell surface proteins and glycans that mediate the entry of Toxin A (TcdA) and Toxin B (TcdB) into colonic epithelial cells. TcdB, the primary driver of human disease, utilizes Frizzled receptors (specifically FZD1, FZD2, and FZD7), Chondroitin sulfate proteoglycan 4 (CSPG4), and Poliovirus receptor-related 3 (PVRL3/Nectin-3) for cell attachment and endocytosis. TcdA interacts with various glycans, glycoprotein 96 (gp96), and members of the low-density lipoprotein receptor family. These receptors are primarily located on the apical brush border of intestinal epithelial cells, where they serve as the initial contact points for luminal toxins. Following receptor binding, the toxins are internalized via endocytosis and subsequently glucosylate Rho-family GTPases, causing cytoskeletal disruption, loss of barrier function, and cell death. Therapeutic strategies targeting these receptors include neutralizing antibodies like bezlotoxumab, which prevents TcdB from binding to its host receptors, and experimental decoy receptors designed to sequester toxins before they can reach the epithelial surface.

Other names

Intestinal epithelial brush border receptors for C. difficile toxinsClostridioides difficile toxin receptorsTcdA receptorsTcdB receptorsFrizzled receptors (FZD1, FZD2, FZD7)Chondroitin sulfate proteoglycan 4 (CSPG4)Poliovirus receptor-related 3 (PVRL3)Nectin-3Glycoprotein 96 (gp96)Sucrase-isomaltase (SI)Low-density lipoprotein receptor (LDLR)Low-density lipoprotein receptor-related protein 1 (LRP1)

Toxin neutralization, Competitive inhibition of receptor binding, Blocking endocytosis