Impact of Anti-Shiga Toxin Type 2 (Stx2) Neutralizing Antibody on Colonization and Pathogenesis of Escherichia Coli O157:H7 in Mice
Abstract
Escherichia coli O157:H7 was first clearly documented as a human pathogen when it caused an outbreak of hamburger associated bloody diarrhea, or hemorrhagic colitis (HC) in 1982. In the ensuing years, E. coli O157:H7 has been responsible for multiple food- and water-borne outbreaks of diarrhea and/or HC worldwide. A portion (4-15%) of such E. coli O157:H7-infected individuals develop a life-threatening sequela of infection called hemolytic uremic syndrome or HUS. The major virulence factor that has been linked to both the presentation of HC and HUS is Shiga toxin (Stx), a potent cytotoxin that can cause inhibition of protein synthesis in sensitive target cells such as in the kidneys. The goal of this research was to help elucidate the course of E. coli O157:H7 pathogenesis to facilitate treatment and prevention of disease. For that purpose, we first developed a conventional mouse model in which the E. coli O157:H7 introduced by pipette feeding or gavage had to compete with the resident microbiota to establish infection. This intact commensal flora (ICF) adult mouse model is one of the few such murine models described to date that permits the evaluation of both colonization by E. coli O157:H7 and the subsequent systemic disease associated with Stx production. Through the use of this ICF model, we next went on to demonstrate not only a role for Stx in E. coli O157:H7 colonization, but more importantly, a role for anti-Stx antibody in reducing colonization. Our results suggest that a vaccine to reduce E. coli O157:H7 disease should include a toxoid component not only because anti-toxin antibodies would prevent Stx toxicity but also because anti-toxin antibodies may reduce bacterial colonization. Thus, we propose that our animal model and findings on colonization by E. coli O157:H7 and the subsequent impact of Stx produced in the gut may further advance the development and use of toxoid-based vaccines and therapeutic strategies against E. coli O157:H7.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 17, 2010
- Accession Number
- ADA539384
Entities
People
- Krystle L. Mohawk
Organizations
- Uniformed Services University of the Health Sciences