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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Citrobacter rodentium Relies on Commensals for Colonization of the Colonic Mucosa
Caroline Mullineaux-Sanders1, James W Collins1, David Ruano-Gallego1
1MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, UK.
Abstract:
We investigated the role of commensals at the peak of infection with the colonic mouse pathogen Citrobacter rodentium. Bioluminescent and kanamycin (Kan)-resistant C. rodentium persisted avirulently in the cecal lumen of mice continuously treated with Kan. A single Kan treatment was sufficient to displace C. rodentium from the colonic mucosa, a phenomenon not observed following treatment with vancomycin (Van) or metronidazole (Met). Kan, Van, and Met induce distinct dysbiosis, suggesting C. rodentium relies on specific commensals for colonic colonization. Expression of the master virulence regulator ler is induced in germ-free mice, yet C. rodentium is only seen in the cecal lumen. Moreover, in conventional mice, a single Kan treatment was sufficient to displace C. rodentium constitutively expressing Ler from the colonic mucosa. These results show that expression of virulence genes is not sufficient for colonization of the colonic mucosa and that commensals are essential for a physiological infection course.
Insights
Commensal bacteria are essential for Citrobacter rodentium colonization of the mouse colon. Antibiotic treatments that alter gut microbiota composition, like kanamycin, displace this pathogen, highlighting the role of specific commensals in infection.
Area of Science:
- Microbiology
- Gastroenterology
- Infectious Diseases
Background:
- Citrobacter rodentium is a mouse pathogen that infects the colon.
- The role of commensal bacteria during C. rodentium infection is not fully understood.
Purpose of the Study:
- To investigate the role of commensals in C. rodentium colonization of the colonic mucosa.
- To determine if virulence gene expression is sufficient for mucosal colonization.
Main Methods:
- Mice were infected with Citrobacter rodentium and treated with antibiotics (kanamycin, vancomycin, metronidazole).
- Bioluminescent and antibiotic-resistant C. rodentium strains were used to track colonization.
- Virulence gene expression (ler) was monitored.
Main Results:
- Kanamycin treatment displaced C. rodentium from the colonic mucosa, unlike vancomycin or metronidazole.
- Distinct dysbiosis was induced by the different antibiotics, suggesting reliance on specific commensals.
- C. rodentium expressing the ler virulence gene was still displaced from the mucosa by kanamycin.
Conclusions:
- Commensal bacteria are essential for Citrobacter rodentium to colonize the colonic mucosa.
- Virulence gene expression alone is insufficient for mucosal colonization.
- Commensals play a critical role in the physiological course of C. rodentium infection.
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