The object of this proposed research is to identify and characterize the macromolecules that allow the bacterium Citrobacter freundii biotype 4280 to induce epithelial cell proliferation in the descending colon of laboratory mice. This disease, called transmissible murine colonic hyperplasia, results in altered intestinal physiology which resembles that of human proliferative bowel disorders. Consequently, mice with transmissible murine colonic hyperplasia develop colonic neoplasia after a shorter latent period and with a lower dose than uninfected mice, following exposure to a known carcinogen. This work may ultimately lead to the development of a mouse model for inflammatory bowel disease, and a better understanding of the relationship between gastrointestinal pathogens, mucosal turnover, and cancer.
