Biological mode of action of Clostridium difficile toxin A: a novel enterotoxin

Department of Microbiology, University of Birmingham, P.O. Box 363, Birmingham B15 2TT, * The General Hospital, Steelhouse Lane, Birmingham B4 6NH Institute of Child Health, Francis Road, Birmingham B16 8ET Correspondence should be sent to Dr J. Stephen, Department of Microbiology, University of Birmingham, Birmingham BT15 2TT. Received May 12, 1986 Accepted July 23, 1986 Antibody neutralisation and toxin A elution experiments showed that toxin A uptake from rabbit intestinal lumen was a continuous process. The kinetics of the ileal and colonic responses were significantly different; a much longer incubation (4 h) with toxin was required for colon, compared with 45 min for the ileum, to induce fluid accumulation at 12 h. Fluid secretion was induced only when toxin had gained access to deeper tissues, probably achieved by several toxin uptake-tissue damage cycles. Toxin A induced haemorrhage in both ileal and colonic tissues. In ileum, the villus architecture was severely damaged and this gave rise to protein-rich bloody luminal fluid. In the colon, although colonocytes were removed, the basement membrane remained intact; this resulted in a tissue-localised haemorrhage and a protein-low watery ultrafiltered luminal fluid. Toxin A is thus a novel type of histotoxic enterotoxin.