CLINICAL SIGNS AND LESIONS IN GNOTOBIOTIC PIGS INOCULATED WITH SHIGA-LIKE TOXIN-I FROM ESCHERICHIA-COLI

Gnotobiotic pigs were used as a model to study the contribution of Shi ga-like toxin I to natural disease caused by enterohemorrhagic Escheri chia coli in calves and human beings. Eleven 2- to 7-day-old gnotobiot ic pigs of either sex, obtained by closed hysterotomy, were injected i ntramuscularly with graded doses of partially purified Shiga-like toxi n I derived from a lysogenized Escherichia coli strain. Four other gno tobiotic pigs were injected with a mock toxin preparation obtained fro m a nonlysogenized culture of the same E. coli strain. All toxin-injec ted pigs developed diarrhea, and three displayed signs of neurologic d isease. Pigs either died or were euthanatized 2 to 4 days post-inocula tion. 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 toxi n-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 vess els at lesion sites, endothelial cells were frequently swollen or necr otic. Pigs inoculated with mock toxin did not develop diarrhea or exhi bit signs of neurologic disease, and the only apparent lesion was mild microscopic myositis at the injection site in 1/4 pigs. The results o f this study indicate that Shiga-like toxin I causes vascular damage a nd ischemic necrosis in the intestines and brains of gnotobiotic pigs. These lesions are similar to those seen in the intestines of calves a nd human beings with hemorrhagic colitis and in the brains of human be ings with thrombotic thrombocytopenic purpura.