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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Emergence of a 'hyperinfectious' bacterial state after passage of Citrobacter rodentium through the host
Siouxsie Wiles1, Gordon Dougan, Gad Frankel
1Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College London, London SW7 2AZ, UK.
Abstract:
Citrobacter rodentium belongs to a family of human and animal enteric pathogens that includes the clinically significant enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). These pathogens exploit attaching and effacing (A/E) lesions to colonize the host gastrointestinal tract. However, both EHEC and EPEC are poorly pathogenic in mice. In contrast, C. rodentium, which is genetically highly related to E. coli, relies on A/E lesion formation as an essential step in both colonization and infection of the murine mucosa, providing an excellent in vivo model. In this study we have used bioluminescence imaging (BLI) to investigate the organ specificity and dynamics of colonization of mice by LB-grown and mouse-passaged C. rodentium in situ and in real time. We have demonstrated the appearance of a 'hyperinfectious' state after passage of C. rodentium through the murine gastrointestinal tract. The 'hyperinfectious' state was found to dramatically reduce the dose required to infect secondary individuals, and also influenced the tissue distribution of colonizing bacteria, removing the requirement for primary colonization of the caecal patch. In addition, the 'hyperinfectious' phenotype was found to be transient with one overnight passage in rich medium sufficient to return C. rodentium to 'culture' infectivity.
Insights
Citrobacter rodentium gains a hyperinfectious state after mouse gut passage, reducing infection dose and altering tissue colonization. This transient state reverts to normal infectivity after in vitro culture.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Citrobacter rodentium is an enteric pathogen related to E. coli.
- It causes attaching and effacing (A/E) lesions for colonization.
- Unlike EHEC/EPEC, C. rodentium is a suitable mouse model for A/E pathogens.
Purpose of the Study:
- Investigate organ specificity and colonization dynamics of C. rodentium in mice.
- Characterize the 'hyperinfectious' state induced by murine gastrointestinal tract passage.
- Understand the implications of this state on infection dose and tissue tropism.
Main Methods:
- Utilized bioluminescence imaging (BLI) for real-time, in situ monitoring of C. rodentium colonization in mice.
- Compared colonization dynamics of LB-grown and mouse-passaged C. rodentium.
- Assessed infectivity and tissue distribution following different passage methods.
Main Results:
- Demonstrated the emergence of a 'hyperinfectious' state in C. rodentium after passage through the murine gut.
- This state significantly reduced the infectious dose for secondary hosts.
- Observed altered tissue distribution, bypassing initial caecal patch colonization.
Conclusions:
- Murine gut passage induces a transient 'hyperinfectious' phenotype in Citrobacter rodentium.
- This phenotype enhances bacterial transmission potential and alters colonization patterns.
- Standard laboratory culture conditions rapidly restore C. rodentium to its non-hyperinfectious state.
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