Mouse models of Escherichia coli O157:H7 infection and shiga toxin injection.

Krystle L Mohawk,Alison D O'Brien

doi:10.1155/2011/258185

Abstract

Escherichia coli O157:H7 has been responsible for multiple food- and waterborne outbreaks of diarrhea and/or hemorrhagic colitis (HC) worldwide. More importantly, a portion of E. coli O157:H7-infected individuals, particularly young children, develop a life-threatening sequela of infection called hemolytic uremic syndrome (HUS). Shiga toxin (Stx), a potent cytotoxin, is the major virulence factor linked to the presentation of both HC and HUS. Currently, treatment of E. coli O157:H7 and other Stx-producing E. coli (STEC) infections is limited to supportive care. To facilitate development of therapeutic strategies and vaccines for humans against these agents, animal models that mimic one or more aspect of STEC infection and disease are needed. In this paper, we focus on the characteristics of various mouse models that have been developed and that can be used to monitor STEC colonization, disease, pathology, or combinations of these features as well as the impact of Stx alone.

Highlights

IntroductionEscherichia coli O157:H7 is a member of a group of pathogenic E. coli (known as enterohemorrhaghic E. coli or EHEC) that colonize the gastrointestinal tract and cause a condition known as hemorrhagic colitis (HC) or bloody diarrhea
Escherichia coli O157:H7 is a member of a group of pathogenic E. coli that colonize the gastrointestinal tract and cause a condition known as hemorrhagic colitis (HC) or bloody diarrhea
The capacity of Shiga toxin-producing E. coli (STEC) in general and E. coli O157:H7 and other EHEC in particular to produce Shiga toxin (Stx) makes them of particular concern because Stx has been linked to the development of hemolytic uremic syndrome (HUS) that can lead to kidney failure, in children [1, 2]

Summary

Introduction

Escherichia coli O157:H7 is a member of a group of pathogenic E. coli (known as enterohemorrhaghic E. coli or EHEC) that colonize the gastrointestinal tract and cause a condition known as hemorrhagic colitis (HC) or bloody diarrhea. Numerous in vitro assays and animal models have been developed in an attempt to mimic various aspects of E. coli O157:H7 disease in humans In vitro systems such as cell monolayers, transwells, organoids, and in vitro organ culture (referred to as IVOC) as well as ex vivo cultures of biopsies are useful for the study of several aspects of E. coli O157:H7 pathogenesis, such as adherence of the microbe to eukaryotic cells and the impact of Stx on those cells. While each applicable model can be used to study one or more components of the steps in the pathogenesis of E. coli O157:H7- or other STECmediated disease (from initial colonization to mortality), no one animal model system that mimics the full spectrum of STEC-evoked illness in humans (to include the development of HC and HUS) has been described to date (reviewed in [74]). Naturally occurring HUS-like diseases have been described in greyhounds (known as idiopathic cutaneous and renal glomerular vasculopathy of greyhounds (CRVGs) or “Alabama rot” [87, 92]) and rabbits [93]

Mouse Models of Infection

Inoculation Method Feeding

Mouse Models of Intoxication

Applications of Mouse Models

Findings

Conclusions