Critical role of zinc in a new murine model of enterotoxigenic Escherichia coli diarrhea
Date
2018Journal
Infection and ImmunityPublisher
American Society for MicrobiologyType
Article
Metadata
Show full item recordAbstract
Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveler's diarrhea as well as of endemic diarrhea and stunting in children in developing areas. However, a small-mammal model has been badly needed to better understand and assess mechanisms, vaccines, and interventions. We report a murine model of ETEC diarrhea, weight loss, and enteropathy and investigate the role of zinc in the outcomes. ETEC strains producing heat-labile toxins (LT) and heat-stable toxins (ST) that were given to weaned C57BL/6 mice after antibiotic disruption of normal microbiota caused growth impairment, watery diarrhea, heavy stool shedding, and mild to moderate intestinal inflammation, the latter being worse with zinc deficiency. Zinc treatment promoted growth in zinc-deficient infected mice, and subinhibitory levels of zinc reduced expression of ETEC virulence genes cfa1, cexE, sta2, and degP but not of eltA in vitro. Zinc supplementation increased shedding and the ileal burden of wild-type (WT) ETEC but decreased shedding and the tissue burden of LT knockout (LTKO) ETEC. LTKO ETEC-infected mice had delayed disease onset and also had less inflammation by fecal myeloperoxidase (MPO) assessment. These findings provide a new murine model of ETEC infection that can help elucidate mechanisms of growth, diarrhea, and inflammatory responses as well as potential vaccines and interventions. Copyright 2018 American Society for Microbiology.Sponsors
This work was supported in part by Opportunity ID OPP1137923 (Host, pathogen and pathogen interaction determinants of environmental enteric dysfunction) from the Bill & Melinda Gates Foundation and in part by NIH award U19 AI109776 (CETR [Centers for Excellence for Translational Research]; principal investigator [PI], Myron Levine) from the National Institute of Allergy and Infectious Diseases (NIAID). S.E.L. was supported by the Global Infectious Diseases Training (GIDRT) grant D43 TW006578 from the Fogarty International Center at NIH.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050134312&doi=10.1128%2fIAI.00183-18&partnerID=40&md5=94c46e381f29499c4ca77e3b2ba77d16; http://hdl.handle.net/10713/9230ae974a485f413a2113503eed53cd6c53
10.1128/IAI.00183-18
Scopus Count
Collections
Related articles
- Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico.
- Authors: Flores J, DuPont HL, Lee SA, Belkind-Gerson J, Paredes M, Mohamed JA, Armitige LY, Guo DC, Okhuysen PC
- Issue date: 2008 Aug
- Enterotoxigenic Escherichia coli Heat-Stable Toxin Increases the Rate of Zinc Release from Metallothionein and Is a Zinc- and Iron-Binding Peptide.
- Authors: Kiefer MC, Motyka NI, Clements JD, Bitoun JP
- Issue date: 2020 Apr 1
- Enterotoxigenic Escherichia coli Adhesin-Toxoid Multiepitope Fusion Antigen CFA/I/II/IV-3xSTa<sub>N12S</sub>-mnLT<sub>G192G/L211A</sub>-Derived Antibodies Inhibit Adherence of Seven Adhesins, Neutralize Enterotoxicity of LT and STa Toxins, and Protect Piglets against Diarrhea.
- Authors: Nandre R, Ruan X, Lu T, Duan Q, Sack D, Zhang W
- Issue date: 2018 Mar
- Escherichia coli enterotoxigénica y enteroagregativa: prevalencia, patogénesis y modelos múridos.
- Authors: Ríos-Muñiz D, Cerna-Cortés JF, Morán-García N, Meza-Segura M, Estrada-García T
- Issue date: 2019
- CEACAMs serve as toxin-stimulated receptors for enterotoxigenic <i>Escherichia coli</i>.
- Authors: Sheikh A, Tumala B, Vickers TJ, Alvarado D, Ciorba MA, Bhuiyan TR, Qadri F, Singer BB, Fleckenstein JM
- Issue date: 2020 Nov 17