Longitudinal Analysis of Competitive Pathogenesis

Longitudinal Analysis of Competitive Pathogenesis

Jerry Falwell Library, Lower Esbenshade Atrium

Enterohemorrhagic Escherichia coli (EHEC) is a bacterium causing bloody diarrhea and hemolytic uremic syndrome. Citrobacter rodentium, a murine pathogen, is routinely used to model EHEC infections in mice. The genes causing transmissible murine colonic hyperplasia are found in EHEC as well as in C. rodentium.

Treatment with streptomycin eliminates facultative anaerobes from the murine intestine, allowing study of facultative interactions in vivo while preserving the majority of the intestinal microbiota.

C. rodentium causes disease in conventional mice; however, it does not in streptomycin-treated mice. Colonization, therefore, is not sufficient for pathogenesis; there must be other facultative anaerobes present for disease to occur. Competition with certain E. coli strains causes pathogenesis by an unknown mechanism.

If the competition-induced disease state is similar to disease caused by C. rodentium in conventional mice, inducing pathogenesis via competition will be relevant to EHEC modeling. Determination of colonic weight and longitudinal studies of the intestinal microbiota during induced pathogenesis will reveal whether competitive pathogenesis resembles normal disease.

I hypothesize that competition-induced disease in streptomycin-treated mice will resemble disease caused by C. rodentium in conventional mice and that changes in the intestinal microbiota will also be similar.