Date of Award
Doctor of Philosophy
Mark R. Ackermann
Hemolytic Uremic Syndrome (HUS), the leading cause of acute renal failure in children in the United States, is a systemic complication of Enterohemorrhagic Escherichia coli (EHEC) infection that is caused by the systemic effects of Shiga toxins (Stx) produced by EHEC. Every year approximately 70,000 people in the United States are infected with EHEC, and up to 10% go on to develop HUS. Although it is known that Stx causes HUS, the mechanism of Stx translocation from the intestinal lumen to the systemic circulation is poorly understood. In vitro studies have shown that migration of neutrophils across polarized mucosal epithelial cells enhances the translocation of Stx, but it is not known if a similar phenomenon occurs in vivo. This dissertation tests the hypothesis that the host inflammatory response allows or enhances the translocation of Stx from the intestinal lumen to the systemic circulation. To test the hypothesis, we developed a 3-day-old pig model of EHEC infection using E. coli O157:H7. Colostrum fed neonatal pigs infected with E. coli O15T:H7 at 3 days of age, were colonized by E. coli O157:H7 and developed typical attaching and effacing (A/E) lesions, but lacked a histologically detectable inflammatory response and systemic signs and lesions of Stx toxicosis. In the second set of experiments, we induced inflammation in the cecum, spiral colon, and rectum of neonatal pigs using dextran sulfate sodium (DSS). In the final set of experiments, we compared clinical signs and systemic lesions of Stx toxicosis in pigs infected with E. coli O157:H7 with and without a large intestinal inflammatory response, and in pigs orally dosed with crude Stx preparation with and without a large intestinal inflammatory response. We found that severe suppurative and ulcerative inflammation in the large intestine does not enhance Stx translocation from the intestinal lumen to the systemic circulation in vivo. Further work needs to be done to determine the effect of less severe inflammatory changes on Stx translocation.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu
Timothy Wade Morgan
Morgan, Timothy Wade, "The effect of inflammation on Shiga toxin absorption in vivo " (2003). Retrospective Theses and Dissertations. 734.