Frizzled proteins are colonic epithelial receptors for C. difficile toxin B. Academic Article uri icon


  • Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium.

published proceedings

  • Nature

altmetric score

  • 572.662

author list (cited authors)

  • Tao, L., Zhang, J., Meraner, P., Tovaglieri, A., Wu, X., Gerhard, R., ... Dong, M.

citation count

  • 185

complete list of authors

  • Tao, Liang||Zhang, Jie||Meraner, Paul||Tovaglieri, Alessio||Wu, Xiaoqian||Gerhard, Ralf||Zhang, Xinjun||Stallcup, William B||Miao, Ji||He, Xi||Hurdle, Julian G||Breault, David T||Brass, Abraham L||Dong, Min

publication date

  • January 2016

published in