Mouse Models of Escherichia coli O157:H7 Infection and Shiga Toxin Injection

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.

In Vitro and In Vivo Model Systems for Studying Enteropathogenic Escherichia coli Infections

“…Streptomycin-treated mouse models have also been used to study the colonization dynamics of EPEC and EHEC by eliminating or reducing normal gut microbial communities to avoid competitive exclusion and facilitate colonization Mohawk and O'Brien 2011). Bioluminescent strains of EPEC and EHEC show tight association of the bacteria with cecal and colonic tissues of streptomycintreated mice accompanied by mild inflammation Rhee et al 2011) and, in the case of EHEC, microvilli effacement .…”

“…A logical approach to preventing infections in humans has therefore been to immunize cattle to reduce colonization and fecal shedding to the environment. In vivo models such as mice, pigs, and cattle have all been used to study essential virulence factors conserved between EPEC and EHEC as potential vaccine candidates (DeanNystrom et al 2002;Potter et al 2004;McNeilly et al 2010;Misyurina et al 2010;Mohawk and O'Brien 2011). Thus, the EPEC/EHEC T3SS and secreted proteins offer attractive targets for development of novel vaccines and therapeutics whose effectiveness can only be evaluated through in vivo experimentation.…”

Mouse model of Salmonella typhi infection

“…The studies presented in this report show that TLR11 recognizes flagellin from both the UPEC strain 8NU and Salmonella spp. In this regard, it is particularly interesting to note that there are several important flagellated enteropathogenic bacteria, for example enteropathogenic E. coli (Mohawk and O'Brien, 2011) and Campylobacter jujuni (Young et al, 2007), for which mouse models do not recapitulate human disease. Instead, many studies must be carried out using immunocompromised neonatal mice, colonization of germ free and streptomycin treated mice, massive bacterial doses or non-physiological routes of administration, or more limited models such as the rabbit ileal loop or in vitro models.…”

OMV-based vaccine formulations against Shiga toxin producingEscherichia colistrains are both protective in mice and immunogenic in calves

“…37 The two types of Stx (Stx1 and Stx2) are coded in lysogenized phages integrated into the bacterial chromosome. Their expression is induced under conditions that initiate the phage lytic cycle, causing Stx release to the external milieu.…”

“…Although mice are not naturally colonized by STEC strains and do not show the typical A/E lesions, murine models of infection have been developed for evaluating protection by anti-STEC vaccine formulations. 37 One of these models is currently used for studying OMVi-based vaccine formulations with different adjuvants (oleic vs mineral adjuvants), routes of administration (subcutaneous vs intrarectal), and changes on immunogenic composition (production of OMV from the biomass of bacteria grown under different conditions). These experiments will help in the design of an optimized formulation to be directly tested for protection against cattle colonization.…”