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DIFFICILE TOXINS
A major nosocomial pathogen, Clostridium difficile causes antibiotic-associated colitis and intestinal Inflammatory disease, together called CDI. By releasing two large protein enterotoxins, Toxin A (TcdA) and 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, TcdB is many times more potent than TcdA. 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 Toxins A or B, signaling is disrupted leading to the intestinal damage and inflamation characteristic of CDI.
Keyword: clostridial
C. difficile in the news: CDC highlights steps to prevent spread of deadly C. difficile bacteria.
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