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Updated: May 11, 2026

The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux
Nicola K Petty1, Theresa Feltwell, Derek Pickard
1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Abstract:
Citrobacter rodentium is a natural mouse pathogen that causes attaching and effacing (A/E) lesions. It shares a common virulence strategy with the clinically significant human A/E pathogens enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC) and is widely used to model this route of pathogenesis. We previously reported the complete genome sequence of C. rodentium ICC168, where we found that the genome displayed many characteristics of a newly evolved pathogen. In this study, through PFGE, sequencing of isolates showing variation, whole genome transcriptome analysis and examination of the mobile genetic elements, we found that, consistent with our previous hypothesis, the genome of C. rodentium is unstable as a result of repeat-mediated, large-scale genome recombination and because of active transposition of mobile genetic elements such as the prophages. We sequenced an additional C. rodentium strain, EX-33, to reveal that the reference strain ICC168 is representative of the species and that most of the inactivating mutations were common to both isolates and likely to have occurred early on in the evolution of this pathogen. We draw parallels with the evolution of other bacterial pathogens and conclude that C. rodentium is a recently evolved pathogen that may have emerged alongside the development of inbred mice as a model for human disease.
Insights
Citrobacter rodentium exhibits genome instability due to recombination and mobile genetic elements, indicating it is a recently evolved bacterial pathogen. This instability is common across strains and likely occurred early in its evolution.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Evolutionary Biology
Background:
- Citrobacter rodentium is a mouse pathogen causing attaching and effacing (A/E) lesions.
- It models human pathogens like enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC).
- Previous work indicated C. rodentium's genome has characteristics of a newly evolved pathogen.
Purpose of the Study:
- To investigate the genome instability of Citrobacter rodentium.
- To examine the role of recombination and mobile genetic elements in its evolution.
- To assess the representativeness of the ICC168 strain and the timing of mutations.
Main Methods:
- Pulsed-field gel electrophoresis (PFGE).
- Sequencing of variable isolates.
- Whole-genome transcriptome analysis.
- Examination of mobile genetic elements.
- Whole-genome sequencing of an additional strain (EX-33).
Main Results:
- The C. rodentium genome is unstable, driven by repeat-mediated recombination and mobile genetic element transposition (e.g., prophages).
- The EX-33 strain confirms ICC168 is representative of the species.
- Most inactivating mutations are shared between strains, suggesting early evolutionary occurrence.
Conclusions:
- Citrobacter rodentium is a recently evolved pathogen with an unstable genome.
- Its evolution parallels that of other bacterial pathogens.
- Its emergence may be linked to the development of inbred mice models.
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