A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency
A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency
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.
Animals, Anti-Bacterial Agents/administration & dosage, Body Weight, Colon/metabolism, Diarrhea/drug therapy, Disease Models, Animal, Dysentery, Bacillary/drug therapy, Feces/enzymology, Intestinal Mucosa/microbiology, Metabolome, Mice, Inbred C57BL, Mutation, Shigella flexneri/genetics, Type III Secretion Systems/genetics, Zinc/deficiency
615-630
Q.S. Medeiros, Pedro Henrique
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Ledwaba, Solanka E.
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Bolick, David T.
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Giallourou, Natasa
b5891ea7-98d4-49d7-b883-2c57ca2d962a
Yum, Lauren K.
f6180e36-051f-41fc-92f8-22090576b0ad
Costa, Deiziane V.S.
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Oriá, Reinaldo B.
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Barry, Eileen M.
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Swann, Jonathan R.
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Lima, Aldo Ângelo M.
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Agaisse, Hervé
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Guerrant, Richard L.
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2019
Q.S. Medeiros, Pedro Henrique
144b480a-4b68-461b-9a9e-ea4d37cb4a8d
Ledwaba, Solanka E.
d01f5fd8-b8d1-4854-8142-b435f5ef7b84
Bolick, David T.
35949d76-8c51-4889-9a5e-ed52db0eca2c
Giallourou, Natasa
b5891ea7-98d4-49d7-b883-2c57ca2d962a
Yum, Lauren K.
f6180e36-051f-41fc-92f8-22090576b0ad
Costa, Deiziane V.S.
6d63f10b-219a-4f02-90e2-66e341904c7e
Oriá, Reinaldo B.
1acb1b7d-ccfc-4012-833d-aff7b7845f5e
Barry, Eileen M.
68eb53c9-56fa-46bc-bcb0-746b4c8969c1
Swann, Jonathan R.
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Lima, Aldo Ângelo M.
7b08fc40-ffa9-4461-8861-41f891708f7d
Agaisse, Hervé
70f56d6b-31fe-4aab-b9b5-836e3c4da995
Guerrant, Richard L.
b8c9324a-fd9b-401e-b994-105406ee8fbd
Q.S. Medeiros, Pedro Henrique, Ledwaba, Solanka E., Bolick, David T., Giallourou, Natasa, Yum, Lauren K., Costa, Deiziane V.S., Oriá, Reinaldo B., Barry, Eileen M., Swann, Jonathan R., Lima, Aldo Ângelo M., Agaisse, Hervé and Guerrant, Richard L.
(2019)
A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency.
Gut Microbes, 10 (5), .
(doi:10.1080/19490976.2018.1564430).
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.
Text
A murine model of diarrhea growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency
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More information
Accepted/In Press date: 19 December 2018
e-pub ahead of print date: 3 February 2019
Published date: 2019
Keywords:
Animals, Anti-Bacterial Agents/administration & dosage, Body Weight, Colon/metabolism, Diarrhea/drug therapy, Disease Models, Animal, Dysentery, Bacillary/drug therapy, Feces/enzymology, Intestinal Mucosa/microbiology, Metabolome, Mice, Inbred C57BL, Mutation, Shigella flexneri/genetics, Type III Secretion Systems/genetics, Zinc/deficiency
Identifiers
Local EPrints ID: 439798
URI: http://eprints.soton.ac.uk/id/eprint/439798
ISSN: 1949-0976
PURE UUID: 5877875c-cdc4-4393-8529-9d5e1be1a8fe
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Date deposited: 04 May 2020 16:34
Last modified: 17 Mar 2024 04:00
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Contributors
Author:
Pedro Henrique Q.S. Medeiros
Author:
Solanka E. Ledwaba
Author:
David T. Bolick
Author:
Natasa Giallourou
Author:
Lauren K. Yum
Author:
Deiziane V.S. Costa
Author:
Reinaldo B. Oriá
Author:
Eileen M. Barry
Author:
Aldo Ângelo M. Lima
Author:
Hervé Agaisse
Author:
Richard L. Guerrant
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