Long-term selenium deficiency increases the pathogenicity of a Citrobacter rodentium infection in mice

Authors: Smith, Allen; Cheung, Lumei; BOTERO, SEBASTIAN - National Instiute Of Allergy And Infectious Diseases (NIAID, NIH)

Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/28/2011
Publication Date: 5/17/2011
Citation: Smith, A.D., Cheung, L., Botero, S. 2011. Long-term selenium deficiency increases the pathogenicity of a Citrobacter rodentium infection in mice. Biological Trace Element Research. Available: dx.doi.org/10.1007/S12011-011-9071-4.

Interpretive Summary: Citrobacter rodentium is a bacteria that causes disease in mice similar to Escherichia coli in humans and serves as a useful model for studying the immunity to these bacteria. In this study, mice were fed a selenium deficient diet for five or 20 weeks and then infected with C. rodentium. Growth of C. rodentium in the colon was similar in mice fed adequate or selenium deficient diets but more bacteria was found in the spleen in mice fed selenium deficient diet for 20 weeks. Citrobacter rodentium infection of mice fed the selenium deficient diet for 20 weeks had more damage to the colon than mice fed a selenium adequate diet or a selenium deficient diet for only five weeks. Expression of genes associated with an immune response to C. rodentium were higher twelve-days post-infection in mice fed the selenium deficient diet long-term compared to mice fed adequate diet or selenium deficient diet short-term. Diarrhea was prevalent in mice fed the selenium deficient diet long-term but not short-term, and the diarrhea was associated with decreased expression of two genes involved in ion transport in the colon. These results indicated that selenium played an important role in the host’s ability to clear the C. rodentium infection without causing severe damage to the colon. This information is important because it demonstrated that a prolonged absence of selenium from the diet could contribute to greater disease caused by a common food-borne pathogen.

Technical Abstract: Citrobacter rodentium is a mouse pathogen that causes infectious colitis and shares characteristics with human enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli, including the ability to cause attaching and effacing lesions in the colon, and serves as a useful model to study the pathogenicity of these bacteria. In this study, mice were fed a selenium deficient diet for five or 20 weeks and then infected with C. rodentium. Colonization of the colon by C. rodentium was similar in mice fed adequate or selenium deficient diets, but total bacterial colonization of the spleen was elevated in mice fed selenium deficient diet for 20 weeks. Infection induced changes to the colon included inflammatory cell infiltration, gross changes in crypt architecture, and ulceration and denuding of the epithelial layer that were greatest in mice fed a selenium deficient diet for 20 weeks. Expression of pro-inflammatory genes was significantly higher twelve-days post-infection in mice fed the selenium deficient diet for 20 weeks compared to mice fed a selenium adequate diet or selenium deficient diet for five weeks. Diarrhea was prevalent in mice fed the selenium deficient diet for 20 weeks but not five weeks, and this was associated with decreased expression of solute carrier family 26a3 and carbonic anhydrase IV genes involved in ion transport. These results indicate that selenium played an important role in resistance to the pathological effects of a C. rodentium infection and, therefore, selenium status may be important in the expression of human disease caused by common food-borne bacteria.