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    Genome-wide Analysis of Salmonella enterica serovar Typhi in Humanized Mice Reveals Key Virulence Features

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    Authors
    Karlinsey, Joyce E.
    Stepien, Taylor A.
    Mayho, Matthew
    Singletary, Larissa A.
    Bingham-Ramos, Lacey K.
    Brehm, Michael A.
    Greiner, Dale L.
    Shultz, Leonard D.
    Gallagher, Larry A.
    Bawn, Matt
    Kingsley, Robert A.
    Libby, Stephen J.
    Fang, Ferric C.
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    UMass Chan Affiliations
    Diabetes Center of Excellence
    Program in Molecular Medicine
    Document Type
    Journal Article
    Publication Date
    2019-09-11
    Keywords
    PhoP
    SPI-2
    Salmonella Typhi
    TraDIS
    Vi
    humanized mice
    salmochelin
    transposon library
    typhoid toxin
    virulence
    Bacterial Infections and Mycoses
    Cell Biology
    Immunopathology
    Microbiology
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    Link to Full Text
    https://doi.org/10.1016/j.chom.2019.08.001
    Abstract
    Salmonella enterica serovar Typhi causes typhoid fever only in humans. Murine infection with S. Typhimurium is used as a typhoid model, but its relevance to human typhoid is limited. Non-obese diabetic-scid IL2rgammanull mice engrafted with human hematopoietic stem cells (hu-SRC-SCID) are susceptible to lethal S. Typhi infection. In this study, we use a high-density S. Typhi transposon library in hu-SRC-SCID mice to identify virulence loci using transposon-directed insertion site sequencing (TraDIS). Vi capsule, lipopolysaccharide (LPS), and aromatic amino acid biosynthesis were essential for virulence, along with the siderophore salmochelin. However, in contrast to the murine S. Typhimurium model, neither the PhoPQ two-component system nor the SPI-2 pathogenicity island was required for lethal S. Typhi infection, nor was the CdtB typhoid toxin. These observations highlight major differences in the pathogenesis of typhoid and non-typhoidal Salmonella infections and demonstrate the utility of humanized mice for understanding the pathogenesis of a human-specific pathogen.
    Source

    Cell Host Microbe. 2019 Sep 11;26(3):426-434.e6. doi: 10.1016/j.chom.2019.08.001. Epub 2019 Aug 22. Link to article on publisher's site

    DOI
    10.1016/j.chom.2019.08.001
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/44394
    PubMed ID
    31447308
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.chom.2019.08.001
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