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Updated: Feb 27, 2026
The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity
Stefanie Buschor1,2, Miguelangel Cuenca1,2, Stephanie S Uster1
1Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
Abstract:
Citrobacter rodentium infection is a mouse model for the important human diarrheal infection caused by enteropathogenic E. coli (EPEC). The pathogenesis of both species is very similar and depends on their unique ability to form intimately epithelium-adherent microcolonies, also known as "attachment/effacement" (A/E) lesions. These microcolonies must be dynamic and able to self-renew by continuous re-infection of the rapidly regenerating epithelium. It is unknown whether sustained epithelial A/E lesion pathogenesis is achieved through re-infection by planktonic bacteria from the luminal compartment or local spread of sessile bacteria without a planktonic phase. Focusing on the earliest events as C. rodentium becomes established, we show here that all colonic epithelial A/E microcolonies are clonal bacterial populations, and thus depend on local clonal growth to persist. In wild-type mice, microcolonies are established exclusively within the first 18 hours of infection. These early events shape the ongoing intestinal geography and severity of infection despite the continuous presence of phenotypically virulent luminal bacteria. Mechanistically, induced resistance to A/E lesion de-novo formation is mediated by TLR-MyD88/Trif-dependent signaling and is induced specifically by virulent C. rodentium in a virulence gene-dependent manner. Our data demonstrate that the establishment phase of C. rodentium pathogenesis in vivo is restricted to a very short window of opportunity that determines both disease geography and severity.
Insights
Citrobacter rodentium establishes infections through local clonal growth, not re-infection. Early infection events within 18 hours dictate disease severity and location, independent of luminal bacteria.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Citrobacter rodentium infection in mice models human enteropathogenic E. coli (EPEC) infections.
- Both pathogens cause diarrheal disease via attachment/effacement (A/E) lesions on the intestinal epithelium.
- Pathogenesis relies on dynamic microcolonies capable of self-renewal through epithelial re-infection.
Purpose of the Study:
- To investigate whether sustained A/E lesion pathogenesis results from re-infection by planktonic bacteria or local spread.
- To elucidate the mechanisms governing the early establishment of C. rodentium infections.
- To determine the critical time window for C. rodentium colonization and its impact on disease progression.
Main Methods:
- Utilized a mouse model of Citrobacter rodentium infection.
- Analyzed the clonal origin and growth patterns of colonic epithelial A/E microcolonies.
- Investigated the role of TLR-MyD88/Trif-dependent signaling in induced resistance to A/E lesion formation.
Main Results:
- All colonic epithelial A/E microcolonies are clonal bacterial populations, indicating reliance on local growth.
- Microcolonies are established exclusively within the first 18 hours of infection in wild-type mice.
- TLR-MyD88/Trif signaling, induced by virulent C. rodentium, mediates resistance to new lesion formation.
Conclusions:
- The establishment of C. rodentium infection is restricted to a narrow early window (18 hours).
- Local clonal growth, not luminal re-infection, is the primary mechanism for A/E microcolony persistence.
- Early infection events significantly shape the overall disease geography and severity.
