1. A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency.
- Author
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Q S Medeiros PH, Ledwaba SE, Bolick DT, Giallourou N, Yum LK, Costa DVS, Oriá RB, Barry EM, Swann JR, Lima AÂM, Agaisse H, and Guerrant RL
- 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
- 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.
- Published
- 2019
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