Genome-wide Analysis of Salmonella enterica serovar Typhi in Humanized Mice Reveals Key Virulence Features.
Document Type
Article
Publication Date
9-11-2019
Keywords
JMG
JAX Source
Cell Host Microbe 2019 Sep 11; 26(3):426-434.e6
Volume
26
Issue
3
First Page
426
Last Page
434
ISSN
1934-6069
PMID
31447308
DOI
https://doi.org/10.1016/j.chom.2019.08.001
Grant
CA034196
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.
Recommended Citation
Karlinsey J,
Stepien T,
Mayho M,
Singletary L,
Bingham-Ramos L,
Brehm M,
Greiner D,
Shultz LD,
Gallagher L,
Bawn M,
Kingsley R,
Libby S,
Fang F.
Genome-wide Analysis of Salmonella enterica serovar Typhi in Humanized Mice Reveals Key Virulence Features. Cell Host Microbe 2019 Sep 11; 26(3):426-434.e6