Citrobacter Rodentium

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A Microbial Biorealm page on the genus Citrobacter Rodentium


Higher order taxa

Bacteria(Domain); Proteobacteria(Phylum); Gammaproteobacteria(Class); Enterobacteriales(Family); Enterobacteriaceae(Order); Citrobacter(Family) (3)


Citrobacter rodentium (3)

Description and significance

Citrobacter rodentium is a gram negative bacterium which was previously known as Citrobacter freundii biotype 4280 and Citrobacter species 9. It is one of the 9 species belonging to genus Citrobacter. It is a rodent equivalent of human Enteropathogenic Escherichia Coli infection (6). Also, it is a restricted mouse pathogen which lives in mouse colon and can survive with or without oxygen. It lives at a moderate temperature, thus is considered as a mesophile (1). Citrobacter rodentium is unable to produce acid from melibiose, sucrose, dulcitol, or glycerol, yet its ability to produce malonate reaction enables it to use malonate as the only source of carbon. It lacks motility and endospores, which are further significant characteristic of this species. Citrobacter rodentium was isolated from a mouse and was grown in Luria-Bertani agar at 37C. Then, in order to obtain the cells for extraction of DNA, Citrobacter rodentium strains were grown in brain heart infusion broth at around 37C. After, the isolates underwent PCR to be analyzed (10). Isolation and biotyping of Citrobacter rodentium are essential since nonpathogenic but related Citrobacter species can be found in mouse intestine. Also, because this organism contains virulence factors similar to those found in enterohemorrhagic Escherichia coli and enteropathogenic E. coli, its sequence can further provide insights into cytokinetics, cancer risk, and potentially inflammatory bowel disease (13).

Genome structure

Citrobacter rodentium is a gram negative, enteric bacterium. The genome of Citrobacter rodentium is 3,172 nucleotides long. It consists of guanine cytosine content which makes up 46% of the genome. The genome of Citrobacter rodentium is circular and its size is measured to be approximately around 5Mb. Citrobacter rodentium does not have any structural RNA and it also lacks pseudo genes. This genome sequence was completed by University of British Columbia, Biotechnology Laboratory, Canada, Vancouver in September 24th, 2001. (2)

Cell structure and metabolism

Citrobacter rodentium is a gram negative bacterium, which indicates that it has a thin cell wall. Porins, which are located in the outer membrane, serves to regulate the molecules coming in and out of the cellThere are no teichoic acids or lipoteichoic acids around the cell wall. However, it is surrounded by an outer membrane containing lipopolysaccharide, which consists of lipid A, core polysaccharide, and O-polysaccharide. Using metylation analyses, mass spectrometry, and two-dimensional nuclear magnetic resonance spectroscopy, it was found that the antigenic O-polysaccharide consist of 2-acetamido-2-deoxy-D-glucose,D-glucose,and L-rhamnose. Citrobacter rodentium can survive in both anaerobic or aerobic conditions. (9)


Citrobacter rodentium is a mesophile, which requires its environment to be at fairly moderate temperature (1). It lives in the gastrointestinal system of the mice, which is the largest and the most complex environment in the mammalian host. It causes transmissible colonic hyperplasia in mice. Therefore, tt is used as an in vivo model system for the clinically significant A/E pathogens enterohemorrhagic and enteropathogenic Escherichia coli (11).


Citrobacter rodentium is a specific attaching and effacing mouse pathogen which colonize gastrointestinal system. This bacterium first attaches to the intestinal colonocytes, the intestinal epithelial cells. Then it effaces the infected cell microvilli causing hyperplasia and inflammation in infected mice. The complete mechanism of the disease is yet to be clearly known, but some of it has been identified. (10)

It has been found that Citrobacter rodentium uses a type III secretion apparatus to deliver effector molecules into host cells, sabotaging normal cellular function. Mitochondrial associated protein, also known as MAP is a multifunctional effector protein that targets host cell mitochondria and contributes to infection-induced epithelial barrier dysfunction in vitro. Tir, which is the Citrobacter rodentium translocated intimin receptor, is another virulence factor that is responsible for colonic hyperplasia in mice. During the infection, Tir gets translocated into mouse enterocytes in the cell by Citrobacter rodentium. This then provokes the attaching/effacing (A/E) lesion formation which is the major mechanism of tissue targeting and infection. (8)

The mice with colonic hyperplasia Citrobacter rodentium has beginning symptoms of anxiety-like behavior and further develops into overt diarrhea. However, this disease is normally ephemeral in mice, lasting only about 4 weeks. The symptoms are pretty clear thus it’s fairly easy to determine the affected mice, which look obviously sick. Mortality is variable depending on the mice. (4)

Current Research

In a recent study from University of Calgary, Alberta, and The Hospital for Sick Children, Toronto, Ontario, Canada. research was done to find implications for patients who develop an enteric infection during the course of abdominopelvic radiotherapy. The research began knowing that both enteric infection and exposure to ionizing radiation are associated with intestinal permeability. This experiment utilized Citrobacter rodentium to infect the mice then for those mice to be exposed to 5 Gray gamma-radiation about a week later. Then after couple of days, those mice got their colons removed. The result showed that combination of irradiation and infection certainly increased susceptibility to bacterial translocation and bacteremia. (12)

Another research done by The University of British Columbia, Michael Smith Laboratories, looked for the possible contributing factors to diarrhea caused by Citrobacter rodentium infection in mice. In order to do this experiment, the researchers carefully examined whether Citrobacter rodentium infection may alter Aquaporin (AQP) localization in colonocytes. From observation, it was found that mice that recovered from infection in a month period regained their normal membrane AQP localization. Therefore, researchers were able to find out that altered AQP localization can be a possible contributing factor to the symptoms of Citrobacter rodentium infection. (7)

A study was done in 2005 by Chang Gung Children's Hospital and Chang Gung University in Taiwan. In this study, two-week old BALB/c mice were inoculated with the probiotic Lactobacillus acidophilus' twice per week for a month before they were exposed to the Citrobacter rodentium iinfection. They observed that Lactobacillus acidophilus inoculation had an inhibitory effect of preventing the mice from getting colonal infection. This finding greatly decreased the bacteria-induced colitis. This study was also very important because further research can have ramifications for prevention of infectious diarrhea in even humans. (5)


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5. Chen CC, Louie S, Shi HN, Walker WA. "Preinoculation with the probiotic Lactobacillus acidophilus early in life effectively inhibits murine Citrobacter rodentium colitis." Pediatr Res. 2005: 1185-91 <>

6. David B. Schauer, Brian A. Zabel, Isabel F. Pedraza, Caroline M. O'Hara, Arnold G. Steigerwalt, Don J. Brenner."Genetic and Biochemical Characterization of Citrobacter rodentium sp.nov." Journal of Clinical Microbiology, Aug.1995, P.2064~2068 <>

7. Guttman JA, Samji FN, Li Y, Deng W, Lin A, Finlay BB. "Aquaporins contribute to diarrhea caused by attaching and effacing bacterial pathogens." Cell Microbiol. 2007. p.131-41. <>

8. Mac C, Wickham ME, Guttaman JA, Deng W, Walker J, Madsen KL, Jacobson K, Vogl WA, Finlay BB, Vallance BA. "Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo: role of mitochondrial associated protein (Map)." Cell Microbiol. 2006 p.1669-86. <>

9. MacLean LL, Perry MB. "Structural studies on the O-polysaccharide of the lipopolysaccharide produced by Citrobacter rodentium" Eur J Biochem. 2001 Nov;268(22): 5740~6. <>

10. Rosanna Mundy, Thomas T. MacDonald, Gordon Dougan, Gad Frankel, Siouxsie Wiles. "Citrobacter rodentium of mice and man" Cellular Microbiology (2005) 7(12), 1697~1706.<>

11. Skinn AC, Verqnolle N, Zamuner SR, Wallace JL, Cellars L, MacNaughton WK, Sherman PM. "Citrobacter rodentium infection causes iNOS-independent intestinal epithelial dysfunction in mice." Can J Physiol Pharmacol. 2006: 1301-12. <>

12. Skinn AC, Verqnolle N, Cellars L, Sherman PM, MacNaughton WK. "Combined challenge of mice with Citrobacter rodentium and ionizing radiation promotes bacterial translocation." Int J Radiat Biol. 2007: 375-82. <>

13. Steve A. Luperchio, Joseph V. Newman, Charles A. Dangler, Mark D. Schrenzel, Don J. Brenner, Arnold G. Steigerwalt, David B. Schauer. "Citrobacter rodentium, the Causative Agent of Transmissible Murine Colonic Hyperplasia, Exhibits Clonality: Synonymy of C. rodentium and Mouse-Pathogenic Escherichia cooli." J Clin Microbiol.2000 p.4343-4350. <>

Edited by Joanne Hwang

Edited by KLB