Biology and Engineering of Bacterial Toxins
IMM & CLS & LMB & McGovern Joint Research Seminar
Title：Biology and Engineering of Bacterial Toxins
Speaker：Min Dong, Ph.D.
Assistant Professor of Microbiology and Immunobiology
Department of Urology, Boston Children’s Hospital,
Harvard University, USA
Host：北京大学分子医学研究所 周专(Tel. 6275-3212)
Identification of the colonic epithelial receptor for C. difficile toxin B (TcdB) Clostridium difficile toxin B (TcdB) is a critical virulence factor causing diseases associated with C. difficile infection (CDI). How this toxin targets and enters colonic epithelial cells has remained unknown for many years. We recently carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor Frizzled (FZDs) family as physiologically relevant TcdB receptors in the colonic epithelium. Furthermore, we demonstrated that TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signaling, thus revealing a potential new mechanism of pathogenesis for TcdB. This work forms a solid scientific basis for our proposal to further understand the role of FZD-mediated toxin entry in TcdB pathogenesis in vivo in C. difficile infection models, and to explore potential therapeutic approaches by blocking toxin-receptor interactions and by restoring Wnt activity in colonic cells.
Tao L ... Dong M (2016). Frizzled proteins are colonic epithelial receptor for C. difficile toxin B. Nature (article), 538(7625):350-355.