Title

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

UMMS Affiliation

Program in Molecular Medicine; Diabetes Center of Excellence

Publication Date

2019-09-11

Document Type

Article

Disciplines

Bacterial Infections and Mycoses | Cell Biology | Immunopathology | Microbiology

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.

Keywords

PhoP, SPI-2, Salmonella Typhi, TraDIS, Vi, humanized mice, salmochelin, transposon library, typhoid toxin, virulence

DOI of Published Version

10.1016/j.chom.2019.08.001

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

Journal/Book/Conference Title

Cell host and microbe

Related Resources

Link to Article in PubMed

PubMed ID

31447308

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