title: Effects of Clostridium perfringens beta-toxin on the rabbit small intestine and colon.
abstract: Clostridium perfringens type B and type C isolates, which produce beta-toxin (CPB), cause fatal diseases originating in the intestines of humans or livestock. Our previous studies demonstrated that CPB is necessary for type C isolate CN3685 to cause bloody necrotic enteritis in a rabbit ileal loop model and also showed that purified CPB, in the presence of trypsin inhibitor (TI), can reproduce type C pathology in rabbit ileal loops. We report here a more complete characterization of the effects of purified CPB in the rabbit small and large intestines. One microgram of purified CPB, in the presence of TI, was found to be sufficient to cause significant accumulation of hemorrhagic luminal fluid in duodenal, jejunal, or ileal loops treated for 6 h with purified CPB, while no damage was observed in corresponding loops receiving CPB (no TI) or TI alone. In contrast to the CPB sensitivity of the small intestine, the colon was not affected by 6 h of treatment with even 90 mug of purified CPB whether or not TI was present. Time course studies showed that purified CPB begins to induce small intestinal damage within 1 h, at which time the duodenum is less damaged than the jejunum or ileum. These observations help to explain why type B and C infections primarily involve the small intestine, establish CPB as a very potent and fast-acting toxin in the small intestines, and confirm a key role for intestinal trypsin as an innate intestinal defense mechanism against CPB-producing C. perfringens isolates.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Vidal
authors.forename: Bruce A
authors.initials: BA
authors.lastname: McClane
authors.forename: Juliann
authors.initials: J
authors.lastname: Saputo
authors.forename: Jaquelyn
authors.initials: J
authors.lastname: Parker
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Uzal
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000633:toxicity*; D003016:Clostridium perfringens / Q000502:physiology*; D003106:Colon / Q000187:drug effects* / Q000473:pathology*; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D006470:Hemorrhage; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D011817:Rabbits; D013997:Time Factors; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; C031884:CPB protein, Clostridium perfringens; D014361:Trypsin Inhibitors