A major nosocomial pathogen, Clostridium difficile causes antibiotic-associated colitis and intestinal Inflammatory disease, together called CDI.
How does C Difficile Toxin cause diarrhea? By releasing two large protein enterotoxins, C difficile Toxin A (TcdA) and C difficile Toxin B (TcdB), Clostridium difficile mediates inflammatory diarrhea and compromises intestinal epithelial cells. Either toxin when administered to cultured cells disrupts the cytoskeleton and sets off capsase-dependent apoptosis, although, C difficile Toxin B is many times more potent than C difficile Toxin A. Both toxins also activate intestinal epithelial and immune cells to produce cytokines and chemokines, likely contributing to the complications associated with severe CDI. Intracellular targets of TcdA and TcdB are RhoGTPases which regulate many host cell processes including establishing an epithelial barrier and the migration and signaling of immune cells. When the Rho proteins are glycosylated by C difficile Toxins A or B, signaling is disrupted leading to the intestinal damage and inflamation characteristic of CDI.
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