Clostridium difficile is a Gram-positive, anaerobic, spore-forming, toxin-producing bacillus. C. difficile is the most common cause of nosocomial infections in the United States, surpassing methicillin resistant Staphylococcus aureus. Most C. difficile strains produce two major toxins -- TcdA and TcdB, generated by the genes tcdA and tcdB within the organism's Pathogenicity loci. The tcdA gene contains an open reading frame of 8,133 nucleotides, coding for 2,710 amino acids. The molecular weight of C. diff Toxin A is 308 kD. It contains three domains. The active site lies in the amino N-terminal domain and is responsible for the glucosylating activity of the toxin. Both TcdA and TcdB use this highly conserved N-terminal region to alter identical substrates. The carboxy C-terminal domain contains repeating units. These units are responsible for receptor binding on target cell surfaces. These short repeating units determine the potency of TcdA through interactions with structures on the cell surfaces.
TcdA leads to the immediate changes in cell morphology, including loss of structural integrity due to a decrease in filamentous actin and an increase in globular actin. Disorganization of actin filaments and the cytoskeleton leads to increased permeability of tight junctions resulting in severe epithelial cell damage and fluid secretion.
For Research Use Only. NOT FOR CLINICAL USE.
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