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.
Document Type
Journal ArticlePublication Date
2019-09-11Keywords
PhoPSPI-2
Salmonella Typhi
TraDIS
Vi
humanized mice
salmochelin
transposon library
typhoid toxin
virulence
Bacterial Infections and Mycoses
Cell Biology
Immunopathology
Microbiology
Metadata
Show full item recordAbstract
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.2019.08.001Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44394PubMed ID
31447308Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.chom.2019.08.001