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

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.

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Author Karlinsey, Joyce E.
Last Updated November 20, 2019, 16:52 (UTC)
Created November 4, 2019, 17:56 (UTC)
Article Is Open Access false
Citation Report https://scite.ai/reports/10.1016/j.chom.2019.08.001
DOI 10.1016/j.chom.2019.08.001
Funder code(s) National Institutes of Health (AI132963, CA034196, AI112640, OD018259)
Journal Is Open Access false
Open Access Status closed
PDF URL https://reader.elsevier.com/reader/sd/pii/S193131281930366X?token=FC453E17C87D62F1544CA8C71B9531CD0CEBEC815219A2673AEDF5454FD22ABA1FD9A2F6B78D25E3D843C5F37D542915
Publisher URL https://www.sciencedirect.com/science/article/pii/S193131281930366X?via%3Dihub