TOXIN A OF CLOSTRIDIUM DIFFICILE: PRODUCTION, PURIFICATION AND EFFECT IN MOUSE INTESTINE

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Abstract
C. difficile produces 1 diarrheogenic toxin designated A, and 1 cytopathogenic toxin designated B. Toxin A was purified in a 4-step fractionation procedure. In the last purification step, the toxin was separated by elution with galactose from an agarose gel. The purified toxin A induced a clear and watery hypersecretion in intestinal loops of mice; mixtures of toxin A and B induced a hemorrhagic secretion. At an ED50 value for the purified toxin A of 0.5 .mu.g there was a brief, optimal hypersecretion after 4 h. Like the fluid secretion induced by cholera toxin, that induced by toxin A was inhibited by clorpromazine or by depletion of intestinal bile. In contrast to cholera toxin, toxin A did not activate intestinal adenylate cyclase, at least not permanently. Antisera which neutralized cholera toxin did not neutralize toxin A, and vice versa.