THE ROLE OF LIPOPOLYSACCHARIDE AND SHIGA-LIKE TOXIN IN A MOUSE MODEL OF ESCHERICHIA-COLI O157-H7 INFECTION

The role of lipopolysaccharide (LPS) and Shiga-like toxin (SLT) in the pathogenesis of hemolytic uremic syndrome (HUS) was studied in a mous e model. Mice inoculated intragastrically with Escherichia coli O157:H 7 developed gastrointestinal, neurologic, and systemic symptoms, necro tic foci in the colon, glomerular and tubular histopathology, and frag mented erythrocytes. LPS-responder (C3H/HeN) mice developed a combinat ion of neurologic and systemic symptoms, whereas LPS-nonresponder (C3H /HeJ) mice had a biphasic course of disease, first developing systemic symptoms and later severe neurologic symptoms. Mice inoculated with S LT-II-positive strains developed severe neurotoxic symptoms and a high er frequency of systemic symptoms and glomerular pathology compared wi th SLT-II-negative strains. Anti-SLT-II antibodies protected against t hese symptoms and pathology. These results demonstrate that this model could be used to study aspects of human HUS and that both LPS and SLT are important for disease development.