Development of a lethal Shiga toxin-producing Escherichia coli-infection mouse model using multiple mitomycin C treatment.

The aim of this study was to develop a lethal Shiga toxin-producing Escherichia coli (STEC) infection model in mice. A small inoculum of 5 x 10(3) CFU of STEC strain 89020087 to mice treated with streptomycin sulfate in drinking water (5 mg/ml) lead to marked increase in the excretion of the bacteria of up to 10(9)CFU/g feces within 18 h after the challenge. Combination of administration of 5 x 10(3) CFU of STEC followed by mitomycin C (MMC) treatment during the late log phase to the early stationary phase of STEC growth in the intestine lead to fatal infection. Periodic analysis showed that there is transient but dramatic increase in the Stxs (Stx1 and Stx2) concentration in the lower intestines after multiple MMC treatment. Histopathological analysis and blood chemistry revealed damages in both kidney and hematopoietic organs but not in the brain. Comparison of the virulence of 11 different STEC strains revealed that only strains which produced high amount of Stx2 responding to MMC treatment and exerted lethal toxicity to mice, suggesting that Stx2 plays a pivotal role in the lethal infection of STEC in the mouse model.