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A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency.
- Source :
-
Gut microbes [Gut Microbes] 2019; Vol. 10 (5), pp. 615-630. Date of Electronic Publication: 2019 Feb 03. - Publication Year :
- 2019
-
Abstract
- Shigella is one of the major enteric pathogens worldwide. We present a murine model of S. flexneri infection and investigate the role of zinc deficiency (ZD). C57BL/6 mice fed either standard chow (HC) or ZD diets were pretreated with an antibiotic cocktail and received S. flexneri strain 2457T orally. Antibiotic pre-treated ZD mice showed higher S. flexneri colonization than non-treated mice. ZD mice showed persistent colonization for at least 50 days post-infection (pi). S. flexneri -infected mice showed significant weight loss, diarrhea and increased levels of fecal MPO and LCN in both HC and ZD fed mice. S. flexneri preferentially colonized the colon, caused epithelial disruption and inflammatory cell infiltrate, and promoted cytokine production which correlated with weight loss and histopathological changes. Infection with S. flexneri ΔmxiG (critical for type 3 secretion system) did not cause weight loss or diarrhea, and had decreased stool shedding duration and tissue burden. Several biochemical changes related to energy, inflammation and gut-microbial metabolism were observed. Zinc supplementation increased weight gains and reduced intestinal inflammation and stool shedding in ZD infected mice. In conclusion, young antibiotic-treated mice provide a new model of oral S. flexneri infection, with ZD promoting prolonged infection outcomes.
- Subjects :
- Animals
Anti-Bacterial Agents administration & dosage
Body Weight
Colon metabolism
Colon microbiology
Colon pathology
Diarrhea drug therapy
Diarrhea metabolism
Diarrhea microbiology
Dysentery, Bacillary drug therapy
Dysentery, Bacillary metabolism
Dysentery, Bacillary microbiology
Feces enzymology
Feces microbiology
Intestinal Mucosa microbiology
Intestinal Mucosa pathology
Metabolome
Mice, Inbred C57BL
Mutation
Shigella flexneri genetics
Shigella flexneri growth & development
Type III Secretion Systems genetics
Diarrhea pathology
Disease Models, Animal
Dysentery, Bacillary pathology
Shigella flexneri pathogenicity
Zinc deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1949-0984
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Gut microbes
- Publication Type :
- Academic Journal
- Accession number :
- 30712505
- Full Text :
- https://doi.org/10.1080/19490976.2018.1564430