SUMMARY The effect of purified toxin A and partially purified toxin B on rabbit ileum and colon was investigated. Toxin A caused tissue damage which was followed by permeability changes and fluid accumulation in both tissues. Toxin A did not increase the permeability of the colon to the extent observed for ileum; secreted fluid contained less protein of plasma origin. Toxin B had no effect on either tissue. Secretory a-id tissue damaging properties of crude C difficile toxins were found. to be due to toxin A.Clostridium difficile is now known to be the primary cause of antibiotic associated pseudomembranous colitis.1 2 The organism produces four toxins of possible relevance in the pathofenesis of the disease: an enterotoxin (toxin A),3 a cytotoxin (toxin B),3 4 a motility altering factor5 and a recently described labile toxin which causes clear fluid accumulation in rabbit ileal loops.6 In contrast with cholera and Escherichia coli heat labile toxins which induce fluid accumulation with no tissue damage,7 8 toxin A of C difficile causes fluid accumulation with mucosal damage in several animal models: rabbit ileal loop test,9 10 hamster ileal loop9 and hamster caecal loop.9 10 Toxin A is also lethal to mice and causes increased vascular permeability in guinea pig skin.9 Thus toxin A appears to have a mode of action different to that of cholera or E coli heat labile toxins because it causes tissue damage in combination with fluid secretion. Toxin B does not cause fluid accumulation in rabbit ileal loops9 11 or hamster ileal loops. 12 There are discrepancies, however, as to its tissue damag' -g properties:Taylor et a19 report that only limited histological damage is caused to mucosal epithelium of hamster caeca whereas Libby et al'2 showed substantial damage. Toxin B is cytotoxic for a variety of cell lines in vitro but the relevance of this observation to fluid secretion in the intestine is unclear.
SUMMARY. The production and release of toxins A and B by Clostridium dzficile during in-vitro culture was investigated. Cell-associated toxin A was detected by immunoelectrophoresis of bacterial extracts released by ultrasonication and by fluorescent antibody labelling of whole cells. Extracellular toxin A was detected by immunoelectrophoresis and by enzyme-linked immunosorbent assay; extracellular toxin B was detected by cytotoxin assay. Both toxins A and B were produced and released during the decline phase of the bacterial growth cycle; The possible significance of these results in relation to the pathogenesis of pseudomembranous colitis is discussed.
Summary. The kinetics of spore production by Clostridium dzj'icile were not paralleled by release of C. dzficile toxin A in vitro. Toxin A was not found to be associated with either purified whole spores or spore coats. Residual traces of toxin A detected in spore contents were almost certainly derived from contaminating vegetative cell debris. Thus, toxin A is unlikely to be a spore constituent or associated with sporogenesis.
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