ENTEROTOXIC ACTIVITY OF KLEBSIELLA-OXYTOCA CYTOTOXIN IN RABBIT INTESTINAL LOOPS

We examined the enterotoxicity of a Klebsiella oxytoca cytotoxin which is produced by K. oxytoca OK-1, a strain from a patient with antibiotic-associated hemorrhagic colitis. Injection of the cytotoxin into ligated iIeal and colonic loops in rabbits caused the accumulation of fluid in the loops. The fluid was bloody in the ileal loops but not in the colonic ones. Histological examination revealed intense mucosal hemorrhage with erosion in the ileum, whereas no microscopic change was noted in the colon. The fluid accumulation was shown to be a dose-dependent response in both iIeal and colonic loops. The amounts of the cytotoxtin required for maximal fluid accumulation in heal and colonic loops were 60 and 10 mu g, respectively. Fluid accumulation was first noticeable in iIeal loops 12 h and in colonic ones 5 h after the injection of these doses of the cytotoxin and then proceeded with time. When and oxytoca OK-1, a cytotoxin-producing strain, was inoculated into the loops at doses of 1 x 10(8) and 5 x 10(9) CFU, similar fluid accumulation was observed. However, inoculation of K. oxytoca ATCC 13182, a non-cytotoxin-producing strain, at the same doses did not cause any change. These results suggest that the cytotoxin-producing strain of K. oxytoca is the causative organism of antibiotic-associated hemorrhagic colitis and that the toxin is the factor responsible for pathogenesis.