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TFPIisacoloniccryptreceptorforTcdBfromhypervirulentclade2C.difficile

Cell. 2022-03; 
Jianhua Luo , Qi Yang , Xiaofeng Zhang , Yuanyuan Zhang , Li Wan , Xiechao Zhan , Yao Zhou , Liuqing He , Danyang Li , Dazhi Jin , Ying Zhen , Jing Huang , Yanyan Li , Liang Tao
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Codon Optimization mouse Tfpib were codon-optimized, synthesized by Genscript (Nanjing, China) Get A Quote

摘要

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 recogn... More

關鍵詞

CDI pathogenesis; CRISPR/Cas9 screen; Clostridioides difficile; TcdB; clade 2 C. difficile; colonic crypt; cryo-EM structure; receptor; tissue factor pathway inhibitor.
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