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

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. and Fang, Ferric C. (2019) Genome-wide Analysis of Salmonella enterica serovar Typhi in Humanized Mice Reveals Key Virulence Features. Cell Host & Microbe, 26 (3). 426-434.e6. ISSN 1931-3128

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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 IL2rγnull 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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 27 Nov 2019 01:58
Last Modified: 09 Jul 2020 23:57
URI: https://ueaeprints.uea.ac.uk/id/eprint/73073
DOI: 10.1016/j.chom.2019.08.001

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