Shiga toxin 2-induced intestinal pathology in infant rabbits is A-subunit dependent and responsive to the tyrosine kinase and potential ZAK inhibitor imatinib.

Samuel M. Stone, Cheleste M. Thorpe, Amrita Ahluwalia, Arlin B. Rogers, Fumiko Obata, Aimee Vozenilek, Glynis L. Kolling, Anne V. Kane, Bruce E. Magun, Dakshina M. Jandhyala

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Shiga toxin producing Escherichia coli (STEC) are a major cause of food-borne illness worldwide. However, a consensus regarding the role Shiga toxins play in the onset of diarrhea and hemorrhagic colitis (HC) is lacking. One of the obstacles to understanding the role of Shiga toxins to STEC-mediated intestinal pathology is a deficit in small animal models that perfectly mimic human disease. Infant rabbits have been previously used to study STEC and/or Shiga toxin-mediated intestinal inflammation and diarrhea. We demonstrate using infant rabbits that Shiga toxin-mediated intestinal damage requires A-subunit activity, and like the human colon, that of the infant rabbit expresses the Shiga toxin receptor Gb(3). We also demonstrate that Shiga toxin treatment of the infant rabbit results in apoptosis and activation of p38 within colonic tissues. Finally we demonstrate that the infant rabbit model may be used to test candidate therapeutics against Shiga toxin-mediated intestinal damage. While the p38 inhibitor SB203580 and the ZAK inhibitor DHP-2 were ineffective at preventing Shiga toxin-mediated damage to the colon, pretreatment of infant rabbits with the drug imatinib resulted in a decrease of Shiga toxin-mediated heterophil infiltration of the colon. Therefore, we propose that this model may be useful in elucidating mechanisms by which Shiga toxins could contribute to intestinal damage in the human.

Original languageEnglish (US)
Number of pages1
JournalFrontiers in Cellular and Infection Microbiology
Volume2
StatePublished - 2012

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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    Stone, S. M., Thorpe, C. M., Ahluwalia, A., Rogers, A. B., Obata, F., Vozenilek, A., Kolling, G. L., Kane, A. V., Magun, B. E., & Jandhyala, D. M. (2012). Shiga toxin 2-induced intestinal pathology in infant rabbits is A-subunit dependent and responsive to the tyrosine kinase and potential ZAK inhibitor imatinib. Frontiers in Cellular and Infection Microbiology, 2.