Gnotobiotic pigs were used as a model to study the contribution of Shiga-like toxin I to natural disease caused by enterohemorrhagic Escherichia coli in calves and human beings. Eleven 2- to 7-day-old gnotobiotic pigs of either sex, obtained by closed hysterotomy, were injected intramuscularly with graded doses of partially purified Shiga-like toxin I derived from a lysogenized Escherichia coli strain. Four other gnotobiotic pigs were injected with a mock toxin preparation obtained from a nonlysogenized culture of the same E. coli strain. All toxin-injected pigs developed diarrhea, and three displayed signs of neurologic disease. Pigs either died or were euthanatized 2 to 4 days post-inoculation. Necrosis of muscle was grossly evident at the site of injection in all toxin-inoculated pigs. Hemorrhage in the lumen of the small and large intestines and blood in the feces were also evident in two toxin-inoculated pigs. Microscopically, severe necrotizing myositis at the injection site, multifocal encephalomalacia, and mucosal infarcts and hemorrhage in the small and large intestines were seen. In small vessels at lesion sites, endothelial cells were frequently swollen or necrotic. Pigs inoculated with mock toxin did not develop diarrhea or exhibit signs of neurologic disease, and the only apparent lesion was mild microscopic myositis at the injection site in 1/4 pigs. The results of this study indicate that Shiga-like toxin I causes vascular damage and ischemic necrosis in the intestines and brains of gnotobiotic pigs. These lesions are similar to those seen in the intestines of calves and human beings with hemorrhagic colitis and in the brains of human beings with thrombotic thrombocytopenic purpura.
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