A novel murine infection model for Shiga toxin–producing Escherichia coli
Emily M. Mallick, … , John M. Leong, David B. Schauer
Emily M. Mallick, … , John M. Leong, David B. Schauer
Published October 8, 2012
Citation Information: J Clin Invest. 2012;122(11):4012-4024. https://doi.org/10.1172/JCI62746.
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Technical Advance Infectious disease

A novel murine infection model for Shiga toxin–producing Escherichia coli

Abstract

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.

Authors

Emily M. Mallick, Megan E. McBee, Vijay K. Vanguri, Angela R. Melton-Celsa, Katherine Schlieper, Brad J. Karalius, Alison D. O’Brien, Joan R. Butterton, John M. Leong, David B. Schauer

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Figure 2

C. rodentium (λstx2dact) causes lethal infection in mice.

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C. rodentium (λstx2dact) causes lethal infection in mice. (A) Colon...
(A) Colonization of 5-week-old C57BL/6 mice by C. rodentium (λstx2dact), C. rodentium (λstx2dact::kanR), and C. rodentium (DBS100) was determined by viable stool counts. Shown are the average CFU (±SEM) of 5 mice. (B) Fecal water content of mock-infected 5-week-old mice or mice infected with C. rodentium (λstx2dact), C. rodentium (λstx2dact::kanR), or C. rodentium (DBS100). Shown are the averages (±SEM) of groups of 5 mice. Range of average fecal water content of uninfected mice is represented by the vertical bar at 0 days after infection. *P < 0.05 compared with all other groups as determined by 2-way ANOVA followed by Bonferroni post tests. (C) Body weight during infection of 8-week-old mice, expressed as percent change from day 0. Shown are the averages (±SEM) of 5 mice per group. **P < 0.01, ***P < 0.001 compared with all other groups as determined by 2-way ANOVA followed by Bonferroni post tests. (D) Percent survival of groups of five 8-week-old mice that were mock infected or infected with C. rodentium (λstx2dact), C. rodentium (λstx2dact::kanR), or C. rodentium (DBS100). For all panels, results are representative of at least 5 independent experiments.