Animal Models for STEC-Mediated Disease

Abstract

Escherichia coli O157:H7 is the most common infectious cause of bloody diarrhea or hemorrhagic colitis (HC) in the United States (1). The potentially serious nature of infection with E. coli O157:H7 is illustrated by the fact that about 6% of those infected individuals (particularly children) develop a sequela called the hemolytic uremic syndrome or HUS (2). The HUS is characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure, central nervous system involvement, and, in 3–5% of children, death (reviewed in ref.3). E. coli O157:H7 belongs to a subset of Shiga toxin-producing E. coli (STEC) named enterohemorrhagic E. coli (or EHEC) that not only make Shiga toxins (Stxs, formerly called Shiga-like toxins and alternatively known as verotoxins) but also attach to the bowel by a protein called intimin and evoke an attach and efface (A/E) lesion at the site of the bacterial-enterocyte interface (4). The pathogenic process by which E. coli O157:H7 and some other STEC evoke blood in the stools and cause the HUS and the adult version of HUS, thrombotic thrombocytopenic purpura (TTP), remains incompletely understood. Nevertheless, Stx appears to play a pivotal role in these manifestations, and endothelial cells are a primary target of Stx action (5,6). A number of animal species have been tried as models of STEC infection or Stx-mediated disease. However, in no single animal system is there replication of the entire spectrum of the infectious disease process as observed in humans (i.e., in humans, the steps in STEC pathogenesis include oral infection followed by diarrhea, sometimes HC, and occasionally the HUS). Nevertheless, there are animal models that mimic parts of the disease process. These models are described in the following subheadings, with the exception of pig and bovine models, which are described elsewhere in this volume. A summary of the animal types, treatments, and outcomes is given in Table 1.

Table 1 Summary of Animal Models, Treatments and Outcomes