7v1n

Publication Abstract from PubMed

The emergence of hypervirulent clade 2 Clostridioides difficile is associated with severe symptoms and accounts for >20% of global infections. TcdB is a dominant virulence factor of C. difficile, and clade 2 strains exclusively express two TcdB variants (TcdB2 and TcdB4) that use unknown receptors distinct from the classic TcdB. Here, we performed CRISPR/Cas9 screens for TcdB4 and identified tissue factor pathway inhibitor (TFPI) as its receptor. Using cryo-EM, we determined a complex structure of the full-length TcdB4 with TFPI, defining a common receptor-binding region for TcdB. Residue variations within this region divide major TcdB variants into 2 classes: one recognizes Frizzled (FZD), and the other recognizes TFPI. TFPI is highly expressed in the intestinal glands, and recombinant TFPI protects the colonic epithelium from TcdB2/4. These findings establish TFPI as a colonic crypt receptor for TcdB from clade 2 C. difficile and reveal new mechanisms for CDI pathogenesis.

TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile.,Luo J, Yang Q, Zhang X, Zhang Y, Wan L, Zhan X, Zhou Y, He L, Li D, Jin D, Zhen Y, Huang J, Li Y, Tao L Cell. 2022 Mar 17;185(6):980-994.e15. doi: 10.1016/j.cell.2022.02.010. PMID:35303428^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.