Clostridium difficile Toxin A and B, cation-dependent UDP-glucose glucosyltransferases, are cellular toxins that inactivate Rho (and Rho family small GTPases) through monoglucosylation of these family members. TcdA elicits effects primarily within the intestinal epithelium. Effects of this monoglucosylation include disregulation of the actin cytoskeleton, cell rounding, cytotoxicity, and altered cellular signaling. Rho proteins are monoglucosylated by Toxin A and B using UDP-glucose as a cosubstrate. Rho, Rac and Cdc42 are included in the Rho subfamilies targeted by both toxins. Low molecular mass GTP-binding proteins that are not modified by Toxin A and B include Ras, Rab, Arf, or Ran subfamilies as well as heterotrimeric G proteins.
