Enteropathogenic Escherichia coli infection induces diarrhea, intestinal damage, metabolic alterations, and increased intestinal permeability in a murine model
Enteropathogenic Escherichia coli infection induces diarrhea, intestinal damage, metabolic alterations, and increased intestinal permeability in a murine model
Enteropathogenic E. coli (EPEC) are recognized as one of the leading bacterial causes of infantile diarrhea worldwide. Weaned C57BL/6 mice pretreated with antibiotics were challenged orally with wild-type EPEC or escN mutant (lacking type 3 secretion system) to determine colonization, inflammatory responses and clinical outcomes during infection. Antibiotic disruption of intestinal microbiota enabled efficient colonization by wild-type EPEC resulting in growth impairment and diarrhea. Increase in inflammatory biomarkers, chemokines, cellular recruitment and pro-inflammatory cytokines were observed in intestinal tissues. Metabolomic changes were also observed in EPEC infected mice with changes in tricarboxylic acid (TCA) cycle intermediates, increased creatine excretion and shifts in gut microbial metabolite levels. In addition, by 7 days after infection, although weights were recovering, EPEC-infected mice had increased intestinal permeability and decreased colonic claudin-1 levels. The escN mutant colonized the mice with no weight loss or increased inflammatory biomarkers, showing the importance of the T3SS in EPEC virulence in this model. In conclusion, a murine infection model treated with antibiotics has been developed to mimic clinical outcomes seen in children with EPEC infection and to examine potential roles of selected virulence traits. This model can help in further understanding mechanisms involved in the pathogenesis of EPEC infections and potential outcomes and thus assist in the development of potential preventive or therapeutic interventions.
antibiotics, diarrhea, enteropathogenic Escherichia coli, enteropathy, inflammation, murine model
Ledwaba, Solanka E.
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Costa, Deiziane V.S.
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Bolick, David T.
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Giallourou, Natasa
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Medeiros, Pedro H.Q.S.
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Swann, Jonathan R.
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Traore, Afsatou N.
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Potgieter, Natasha
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Nataro, James P.
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Guerrant, Richard L.
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17 December 2020
Ledwaba, Solanka E.
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Costa, Deiziane V.S.
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Bolick, David T.
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Giallourou, Natasa
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Medeiros, Pedro H.Q.S.
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Swann, Jonathan R.
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Traore, Afsatou N.
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Potgieter, Natasha
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Nataro, James P.
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Guerrant, Richard L.
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Ledwaba, Solanka E., Costa, Deiziane V.S., Bolick, David T., Giallourou, Natasa, Medeiros, Pedro H.Q.S., Swann, Jonathan R., Traore, Afsatou N., Potgieter, Natasha, Nataro, James P. and Guerrant, Richard L.
(2020)
Enteropathogenic Escherichia coli infection induces diarrhea, intestinal damage, metabolic alterations, and increased intestinal permeability in a murine model.
Frontiers in Cellular and Infection Microbiology, 10, [595266].
(doi:10.3389/fcimb.2020.595266).
Abstract
Enteropathogenic E. coli (EPEC) are recognized as one of the leading bacterial causes of infantile diarrhea worldwide. Weaned C57BL/6 mice pretreated with antibiotics were challenged orally with wild-type EPEC or escN mutant (lacking type 3 secretion system) to determine colonization, inflammatory responses and clinical outcomes during infection. Antibiotic disruption of intestinal microbiota enabled efficient colonization by wild-type EPEC resulting in growth impairment and diarrhea. Increase in inflammatory biomarkers, chemokines, cellular recruitment and pro-inflammatory cytokines were observed in intestinal tissues. Metabolomic changes were also observed in EPEC infected mice with changes in tricarboxylic acid (TCA) cycle intermediates, increased creatine excretion and shifts in gut microbial metabolite levels. In addition, by 7 days after infection, although weights were recovering, EPEC-infected mice had increased intestinal permeability and decreased colonic claudin-1 levels. The escN mutant colonized the mice with no weight loss or increased inflammatory biomarkers, showing the importance of the T3SS in EPEC virulence in this model. In conclusion, a murine infection model treated with antibiotics has been developed to mimic clinical outcomes seen in children with EPEC infection and to examine potential roles of selected virulence traits. This model can help in further understanding mechanisms involved in the pathogenesis of EPEC infections and potential outcomes and thus assist in the development of potential preventive or therapeutic interventions.
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fcimb-10-595266
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Accepted/In Press date: 11 November 2020
Published date: 17 December 2020
Keywords:
antibiotics, diarrhea, enteropathogenic Escherichia coli, enteropathy, inflammation, murine model
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Local EPrints ID: 448400
URI: http://eprints.soton.ac.uk/id/eprint/448400
ISSN: 2235-2988
PURE UUID: 12366436-fe84-485e-9bfe-ab5b6c67d520
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Date deposited: 21 Apr 2021 16:33
Last modified: 18 Mar 2024 03:56
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Contributors
Author:
Solanka E. Ledwaba
Author:
Deiziane V.S. Costa
Author:
David T. Bolick
Author:
Natasa Giallourou
Author:
Pedro H.Q.S. Medeiros
Author:
Afsatou N. Traore
Author:
Natasha Potgieter
Author:
James P. Nataro
Author:
Richard L. Guerrant
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