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    The Role of the AggR Regulon in the Virulence of the Shiga Toxin-Producing Enteroaggregative Escherichia coli Epidemic O104:H4 Strain in Mice

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    Author
    Boisen, N.
    Melton-Celsa, A.R.
    Nataro, J.P.
    Date
    2019
    Journal
    Frontiers in Microbiology
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fmicb.2019.01824
    Abstract
    An O104:H4 Shiga toxin (Stx)-producing enteroaggregative Escherichia coli (EAEC) strain caused a large outbreak of bloody diarrhea and the hemolytic uremic syndrome in 2011. We previously developed an ampicillin (Amp)-treated C57BL/6 mouse model to measure morbidity (weight loss) and mortality of mice orally infected with the prototype Stx-EAEC strain C227-11. Here, we hypothesized that mice fed C227-11 cured of the pAA plasmid or deleted for individual genes on that plasmid would display reduced virulence compared to animals given the wild-type (wt) strain. C227-11 cured of the pAA plasmid or deleted for the known pAA-encoded virulence genes aggR, aggA, sepA, or aar were fed to Amp-treated C57BL/6 mice at doses of 1010–1011CFU. Infected animals were then either monitored for morbidity and lethality for 28 days or euthanized to determine intestinal pathology and colonization levels at selected times. The pAA-cured, aggR, and aggA mutants of strain C227-11 all showed reduced colonization at various intestinal sites. However, the aggR mutant was the only mutant attenuated for virulence as it showed both reduced morbidity and mortality. The aar mutant showed increased expression of the aggregative adherence fimbriae (AAF) and caused greater systemic effects in infected mice when compared to the C227-11 wt strain. However, unexpectedly, both the aggA and aar mutants displayed increased weight loss compared to wt. The sepA mutant did not exhibit altered morbidity or mortality in the Amp-treated mouse model compared to wt. Our data suggest that the increased morbidity due to the aar mutant could possibly be via an effect on expression of an as yet unknown virulence-associated factor under AggR control. Copyright 2019 The Authors.
    Sponsors
    This study was supported by DFF1333-00156 to NB and the National Institutes of Health grants (AI-033096 to JN and AI-020148 to AO?B). Additional support for the investigation was obtained from the Uniformed Services University grant (R0731977 to AO?B).
    Keyword
    diarrhea
    enteroaggregative Escherichia coli
    mouse model
    O104:H4
    Shiga toxin
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072233439&doi=10.3389%2ffmicb.2019.01824&partnerID=40&md5=15b726c6a366649418e7f95f6a38484a; http://hdl.handle.net/10713/11006
    ae974a485f413a2113503eed53cd6c53
    10.3389/fmicb.2019.01824
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