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- W4220682700 endingPage "994.e15" @default.
- W4220682700 startingPage "980" @default.
- W4220682700 abstract "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." @default.
- W4220682700 created "2022-04-03" @default.
- W4220682700 creator A5000183132 @default.
- W4220682700 creator A5002188808 @default.
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- W4220682700 creator A5060822545 @default.
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- W4220682700 creator A5075759707 @default.
- W4220682700 creator A5078063010 @default.
- W4220682700 creator A5085296684 @default.
- W4220682700 date "2022-03-01" @default.
- W4220682700 modified "2023-10-17" @default.
- W4220682700 title "TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile" @default.
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