Department of Microbiology and Physiological Systems; Department of Pathology
Bacterial Infections and Mycoses | Digestive System Diseases | Microbiology
Enterohemorrhagic E. coli (EHEC) is an important subset of Shiga toxin-producing (Stx-producing) E. coli (STEC), pathogens that have been implicated in outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to intestinal epithelium, EHEC generates "attaching and effacing" (AE) lesions characterized by intimate attachment and actin rearrangement upon host cell binding. Stx produced in the gut transverses the intestinal epithelium, causing vascular damage that leads to systemic disease. Models of EHEC infection in conventional mice do not manifest key features of disease, such as AE lesions, intestinal damage, and systemic illness. In order to develop an infection model that better reflects the pathogenesis of this subset of STEC, we constructed an Stx-producing strain of Citrobacter rodentium, a murine AE pathogen that otherwise lacks Stx. Mice infected with Stx-producing C. rodentium developed AE lesions on the intestinal epithelium and Stx-dependent intestinal inflammatory damage. Further, the mice experienced lethal infection characterized by histopathological and functional kidney damage. The development of a murine model that encompasses AE lesion formation and Stx-mediated tissue damage will provide a new platform upon which to identify EHEC alterations of host epithelium that contribute to systemic disease.
shiga toxin, citrobacter rodentium, ehec, hus
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Copyright © 2012, American Society for Clinical Investigation. Publisher PDF posted as allowed by the publisher's author rights policy at http://static.the-jci.org/content_assets/admin/forms/jcicopyright.pdf.
DOI of Published Version
Mallick EM, McBee ME, Vanguri VK, Melton-Celsa AR, Schlieper K, Karalius BJ, O'Brien AD, Butterton JR, Leong JM, Schauer DB. A novel murine infection model for Shiga toxin-producing Escherichia coli. J Clin Invest. 2012;122(11):4012–4024. doi:10.1172/JCI62746. Link to article on publisher's website
Journal of Clinical Investigation
Mallick, Emily M.; McBee, Megan E.; Vanguri, Vijay K.; Melton-Celsa, Angela R.; Schlieper, Katherine; Karalius, Brad J.; O’Brien, Alison D.; Butterton, Joan R.; Leong, John M.; and Schauer, David B., "A novel murine infection model for Shiga toxin-producing Escherichia coli" (2012). GSBS Student Publications. 1798.