Infectious disease

Cell culture and mouse studies suggest inhibiting FZD1, FZD2 and/or FZD7 could help treat Clostridium difficile infection (CDI). In a human cell line treated with TcdB, knockout of FZD1, FZD2 or FZD7 decreased cell rounding, a pathological marker of CDI, compared with normal expression of FZD1, FZD2 and FZD7. In mouse colonic organoids treated with TcdB, FZD7 knockout increased survival compared with normal FZD7 expression, and knockdown of FZD1, FZD2 and FZD7 increased survival compared with FZD7 knockout alone. In a mice receiving injections of truncated TcdB in the colonic lumen, FZD7 knockout decreased epithelial disruption, inflammatory cell infiltration and edema in the colon compared with normal FZD7 expression. Next steps could include testing inhibition of FZD1, FZD2 and/or FZD7 in models of active CDI...