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

Lookup NU author(s): Dr Matt BawnORCiD

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Abstract

© 2019 Elsevier Inc. Virulence determinants of the human-restricted pathogen Salmonella Typhi are incompletely understood. Karlinsey et al. use a high-density transposon library to identify genes required for S. Typhi virulence in humanized mice engrafted with human immune cells. The screen reveals key differences between S. Typhimurium and S. Typhi pathogenesis.© 2019 Elsevier Inc.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.

Publication metadata

Author(s): Karlinsey JE, Stepien TA, Mayho M, Singletary LA, Bingham-Ramos LK, Brehm MA, Greiner DL, Shultz LD, Gallagher LA, Bawn M, Kingsley RA, Libby SJ, Fang FC

Publication type: Article

Publication status: Published

Journal: Cell Host and Microbe

Year: 2019

Volume: 26

Issue: 3

Pages: 426-434.e6

Print publication date: 11/09/2019

Online publication date: 22/08/2019

Acceptance date: 31/07/2019

ISSN (print): 1931-3128

ISSN (electronic): 1934-6069

Publisher: Cell Press

URL: https://doi.org/10.1016/j.chom.2019.08.001

DOI: 10.1016/j.chom.2019.08.001

PubMed id: 31447308

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