Clostridium perfringens Type A Enterotoxin Damages the Rabbit Colon

Abstract

bClostridium perfringens enterotoxin causes the gastrointestinal (GI) symptoms of C. perfringens type A food poisoning and CPE-associated non-food-borne human GI diseases. It is well established that CPE induces fluid accumulation and severe tissue damage in ligated small intestinal loops of rabbits and other animals. However, a previous study had also reported that CPE binds to rabbit colonic cells yet does not significantly affect rabbit colonic loops. To the contrary, the current study determined that treatment with 50 or 100 g/ml of CPE causes significant histologic lesions and luminal fluid accumulation in rabbit colonic loops. Interestingly, a CPE-neutralizing monoclonal antibody blocked the development of CPE-induced histologic damage but not luminal fluid accumulation in these loops. Similar luminal fluid accumulation, without significant histologic damage, also occurred after treatment of colonic loops with heat-inactivated CPE, antibody alone, or bovine serum albumin (BSA), indicating that increased osmolarity was causing or contributing to fluid accumulation in CPE-treated colonic loops. Comparative studies revealed the similar development of histologic damage and luminal fluid accumulation in both small intestinal loops and colonic loops after as little as a 1-h treatment with 50 g/ml of CPE. Consistent with the CPE sensitivity of the small intestine and colon, Western blotting detected CPE binding and large-complex formation in both organs. In addition, Western blotting demonstrated the presence of the high-affinity CPE receptors claudin-3 and -4 in both organs of rabbits, consistent with the observed toxin binding. Collectively, these results offer support for the possible involvement of the colon in CPE-mediated GI disease.

Duodenitis‐Proximal Jejunitis in Horses After Experimental Administration ofClostridium difficileToxins

“…Microscopically, the anatomic sites and severity of the lesions in horses of this study resembled those described for horses with naturally occurring DPJ . A potential dose‐dependent effect of toxins was noted, similar to the dose‐dependent effects caused by C. perfringens enterotoxin in rabbits, associated with the development of histologic lesions in the small and large intestine . In our study, although the most severe lesions occurred in the duodenum and jejunum of the inoculated horses, other tissues including the stomach (pylorus) proximally and the cecum and large colon (pelvic flexure) distally were also mildly affected.…”

“…10 A potential dose-dependent effect of toxins was noted, similar to the dose-dependent effects caused by C. perfringens enterotoxin in rabbits, associated with the development of histologic lesions in the small and large intestine. 23 In our study, although the most severe lesions occurred in the duodenum and jejunum of the inoculated horses, other tissues including the stomach (pylorus) proximally and the cecum and large colon (pelvic flexure) distally were also mildly affected. The lesions observed in the distal part of the GI tract could have been caused by biologically active toxins that reached these segments.…”

Clostridium perfringens type A–E toxin plasmids

“…For example: 1) administration of CPE to human volunteers caused the classical diarrhea observed during natural disease [8]; 2) CPE is detectable in the feces of individuals with C. perfringens type A infection [9]; 3) CPE antisera can inhibit intestinal pathology in experimental animal models [10]; and 4) purified CPE damaged human ileal tissue ex vivo [11]. Perhaps the most persuasive evidence for the pathogenic role of CPE was provided by fulfilling molecular Koch’s postulates for strain SM101 (a type A, chromosomal cpe , food poisoning strain) and F4969 (a type A, plasmid cpe, SD strain), which showed that CPE is essential for these two strains to cause histological damage and fluid accumulation in rabbit ileal loops [12].…”

“…The Ca 2+ influx activates calpain, which can lead to apoptosis (low toxin dose) or necrosis (high toxin dose) [24, 25]. During in vivo disease, CPE-induced cell death leads to the intestinal lesions that trigger fluid accumulation and diarrhea [10, 18]. Upon prolonged contact with the intestines, CPE can be absorbed into the circulation and cause enterotoxemia, affecting organs such as the liver or kidneys [26].…”

Clostridium perfringens enterotoxin

“…It was once thought that only the small intestine is affected by CPE [45], with the ileum being the most sensitive small intestinal region [45]. However, recent studies demonstrated that, at least in the rabbit, the colon is also damaged by the enterotoxin [46].…”