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A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency

Title: A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency
Authors: Q S Medeiros, PH
Ledwaba, SE
Bolick, DT
Giallourou, N
Yum, LK
Costa, DVS
Oriá, RB
Barry, EM
Swann, JR
Lima, AÂM
Agaisse, H
Guerrant, RL
Item Type: Journal Article
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.
Issue Date: 3-Feb-2019
Date of Acceptance: 19-Dec-2018
URI: http://hdl.handle.net/10044/1/69312
DOI: https://doi.org/10.1080/19490976.2018.1564430
ISSN: 1949-0984
Publisher: Taylor & Francis
Start Page: 615
End Page: 630
Journal / Book Title: Gut Microbes
Volume: 10
Issue: 5
Copyright Statement: © 2019 The Author(s). Published with license by Taylor & Francis Group, LLCThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricteduse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Bill & Melinda Gates Foundation
Funder's Grant Number: Prime Award OPP1066140
Keywords: Shigellosis
intestinal microbiota
mouse model
urine metabolomics
zinc deficiency
Shigellosis
intestinal microbiota
mouse model
urine metabolomics
zinc deficiency
0605 Microbiology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-02-03
Appears in Collections:Department of Metabolism, Digestion and Reproduction