Development and application of a mouse intestinal loop model to study the in vivo action of Clostridium perfringens enterotoxin

Justin A. Caserta, Susan L. Robertson, Juliann Saputo, Archana Shrestha, Bruce A. McClane, Francisco A Uzal

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of C. perfringens type A food poisoning, the second most commonly identified bacterial food-borne illness in the United States. CPE is produced by sporulating C. perfringens cells in the small intestinal lumen, where it then causes epithelial cell damage and villous blunting that leads to diarrhea and cramping. Those effects are typically self-limiting; however, severe outbreaks of this food poisoning, particularly two occurring in psychiatric institutions, have involved deaths. Since animal models are currently limited for the study of the CPE action, a mouse ligated intestinal loop model was developed. With this model, significant lethality was observed after 2 h in loops receiving an inoculum of 100 or 200 μg of CPE but not using a 50-μg toxin inoculum. A correlation was noted between the overall intestinal histological damage and lethality in mice. Serum analysis revealed a dose-dependent increase in serum CPE and potassium levels. CPE binding to the liver and kidney was detected, along with elevated levels of potassium in the serum. These data suggest that CPE can be absorbed from the intestine into the circulation, followed by the binding of the toxin to internal organs to induce potassium leakage, which can cause death. Finally, CPE pore complexes similar to those formed in tissue culture cells were detected in the intestine and liver, suggesting that (i) CPE actions are similar in vivo and in vitro and (ii) CPE-induced potassium release into blood may result from CPE pore formation in internal organs such as the liver.

Original languageEnglish (US)
Pages (from-to)3020-3027
Number of pages8
JournalInfection and Immunity
Volume79
Issue number8
DOIs
StatePublished - Aug 2011

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

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