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dc.contributor.authorBolick, D.T.
dc.contributor.authorMedeiros, P.H.Q.S.
dc.contributor.authorLedwaba, S.E.
dc.date.accessioned2019-05-21T18:56:20Z
dc.date.available2019-05-21T18:56:20Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85050134312&doi=10.1128%2fIAI.00183-18&partnerID=40&md5=94c46e381f29499c4ca77e3b2ba77d16
dc.identifier.urihttp://hdl.handle.net/10713/9230
dc.description.abstractEnterotoxigenic 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.en_US
dc.description.sponsorshipThis 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.en_US
dc.description.urihttps://dx.doi.org/10.1128/IAI.00183-18en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofInfection and Immunity
dc.subjectDiarrheaen_US
dc.subjectEnteropathyen_US
dc.subjectETECen_US
dc.subjectLT and STen_US
dc.subjectMurine modelen_US
dc.subjectZincen_US
dc.titleCritical role of zinc in a new murine model of enterotoxigenic Escherichia coli diarrheaen_US
dc.typeArticleen_US
dc.identifier.doi10.1128/IAI.00183-18
dc.identifier.pmid29661930


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