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Updated: Dec 15, 2025
The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Isolation and Characterization of Bacteriophages That Infect Citrobacter rodentium, a Model Pathogen for Intestinal
Carolina M Mizuno1, Tiffany Luong2, Robert Cederstrom2
1Department of Microbiology, Institut Pasteur, 75015 Paris, France.
Abstract:
Enteropathogenic Escherichia coli (EPEC) is a major pathogen for diarrheal diseases among children. Antibiotics, when used appropriately, are effective; however, their overuse and misuse have led to the rise of antibiotic resistance worldwide. Thus, there are renewed efforts into the development of phage therapy as an alternative antibacterial therapy. Because EPEC in vivo models have shortcomings, a surrogate is used to study the mouse pathogen Citrobacter rodentium in animal models. In this study, two new phages CrRp3 and CrRp10, which infect C. rodentium, were isolated and characterized. CrRp3 was found to be a new species within the genus Vectrevirus, and CrRp10 is a new strain within the species Escherichia virus Ime09, in the genus Tequatrovirus. Both phages appear to have independently evolved from E. coli phages, rather than other Citrobacter spp. phages. Neither phage strain carries known genes associated with bacterial virulence, antibiotic resistance, or lysogeny. CrRp3 is more potent, having a 24-fold faster adsorption rate and shorter lytic cycle when compared to the same properties of CrRp10. However, a lysis curve analysis revealed that CrRp10 prevented growth of C. rodentium for 18 h, whereas resistance developed against CrRp3 within 9 h. We also show that hypoxic (5% oxygen) conditions decreased CrRp3 ability to control bacterial densities in culture. In contrast, low oxygen conditions did not affect CrRp10 ability to replicate on C. rodentium. Together, CrRp10 is likely to be the better candidate for future phage therapy investigations.
Insights
Two new phages, CrRp3 and CrRp10, were isolated to combat Citrobacter rodentium, a surrogate for enteropathogenic Escherichia coli. CrRp10 demonstrated superior efficacy in controlling bacterial growth and resilience to low oxygen, making it a promising candidate for phage therapy.
Area of Science:
- Microbiology
- Bacteriology
- Phage Therapy
Background:
- Antibiotic resistance is a growing global health concern, necessitating alternative treatments.
- Enteropathogenic Escherichia coli (EPEC) causes significant diarrheal disease in children.
- Citrobacter rodentium serves as a valuable animal model surrogate for studying EPEC infections.
Purpose of the Study:
- To isolate and characterize novel bacteriophages targeting Citrobacter rodentium.
- To evaluate the therapeutic potential of these phages as alternatives to antibiotics.
- To compare the efficacy of two newly identified phages, CrRp3 and CrRp10.
Main Methods:
- Isolation and characterization of two bacteriophages, CrRp3 and CrRp10, infecting C. rodentium.
- Genomic analysis to identify phage species, genus, and potential virulence/resistance genes.
- Assessment of phage adsorption rates, lytic cycle durations, and bacterial growth inhibition.
- Evaluation of phage efficacy under varying oxygen conditions (hypoxic vs. normoxic).
Main Results:
- CrRp3 identified as a new species in the genus Vectrevirus; CrRp10 as a new strain of Escherichia virus Ime09 (genus Tequatrovirus).
- Both phages evolved from E. coli phages and lack genes for virulence, antibiotic resistance, or lysogeny.
- CrRp10 exhibited longer inhibition of C. rodentium growth (18h vs 9h) and was unaffected by hypoxic conditions, unlike CrRp3.
Conclusions:
- CrRp10 demonstrated superior performance over CrRp3 in controlling C. rodentium growth and maintaining efficacy in low-oxygen environments.
- The findings suggest CrRp10 is a more suitable candidate for further development in phage therapy against C. rodentium infections.
- Phage therapy presents a viable alternative to antibiotics for combating bacterial infections, particularly in the context of rising antibiotic resistance.
