Mouse model for colonization and disease caused by enterohemorrhagic Escherichia coli O157:H7

Abstract

Enterohemorrhagic Escherichia coli O157:H7 isolates produce Shiga-like toxins and carry a 60-megadalton plasmid which encodes an adhesin for Henle 407 intestinal cells. A streptomycin-treated mouse model was used to compare the intestinal colonizing capacity of E. coli O157:H7 strain 933 with that of its 60-megadalton plasmid-cured derivative, strain 933cu. When fed individually to mice, both 933 and 933cu maintained a stable number of organisms per gram of feces, and the greatest numbers of 933 or 933cu were isolated from cecal and proximal colonic epithelial cells. When 933 and 933cu were simultaneously fed to mice, 933cu was unable to maintain a stable level of colonization in about two-thirds of the mice tested. However, in one-third of the mice, the number of 933cu in feces began to increase rapidly until a stable level of co-colonization with 933 was attained. The isolate from these mice, 933cu-rev, was excreted in high numbers when fed alone to mice and was found on epithelial cells throughout the entire large bowel and distal small intestine. Moreover, 933cu-rev grew in mucus from all segments of the intestine and at higher levels than strain 933 or 933cu. Only mice fed strain 933cu-rev died. Histopathological studies confirmed that mice fed 933cu-rev died from bilateral renal cortical tubular necrosis consistent with toxic insult, perhaps due to Shiga-like toxins. The virulence of 933cu-rev may reflect its ability to grow well in mucus and colonize the small as well as large bowel.