A model of Salmonella colitis with features of diarrhea in SLC11A1 wild-type mice
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Updated: Jul 7, 2026
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Heungjeong Woo1, Sharon Okamoto, Donald Guiney
1Department of Infectious Diseases, Veterans Affairs (VA) Healthcare, San Diego, California, United States of America.
Background:
Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1(G169D) allele) die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1(G169)) with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2(Nramp1) congenic started losing weight 5 days post-infection and they began to die from colitis 10-14 days after infection. A SPI-1 (invA) mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPH-deficient (gp91(phox)) mice. However, strain 14028s caused severe colitis and diarrhea in gp91(phox)-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis.
Conclusions:
S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore, a Salmonella phoP mutant can be cleared from the colon by non-oxidative host defenses.
Insights
A new mouse model using ItyR mice pretreated with kanamycin effectively studies Salmonella-induced diarrhea and colitis. This model reveals Salmonella must invade and persist in the colon to cause disease, and NADPH oxidase is not essential for diarrhea.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Mice typically resist Salmonella enterica-induced diarrhea.
- Aminoglycoside pre-treatment enables Salmonella colitis in mice.
- Existing models of Salmonella colitis are limited, necessitating new approaches.
Purpose of the Study:
- To establish and validate a new mouse model for studying Salmonella-induced diarrhea and colitis.
- To investigate the roles of bacterial invasion, persistence, and host factors in Salmonella pathogenesis.
Main Methods:
- Oral infection of ItyR mice (Nramp1(G169)) with S. Typhimurium 14028s after kanamycin pre-treatment.
- Assessment of diarrhea using visual scoring and fecal water content.
- Evaluation of bacterial mutants (SPI-1, phoP-, pmrA, pmrF) and host genetic deficiencies (gp91(phox)) in disease development.
Main Results:
- The established model recapitulated Salmonella colitis and diarrhea in susceptible mice.
- Bacterial invasion and colonic persistence were critical for inducing colitis and diarrhea.
- The NADPH oxidase system was not required for Salmonella-induced diarrhea.
- A phoP- mutant was cleared by non-oxidative host defenses.
Conclusions:
- Salmonella enterica requires colonic epithelial invasion and persistence to cause colitis and diarrhea.
- The host's NADPH oxidase is not essential for the development of Salmonella colitis.
- Host defense mechanisms, beyond oxidative pathways, are crucial for controlling Salmonella phoP mutants in the colon.
