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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Article and Supplementary Information PDFPDF
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PRJNA546274
Sequence data stored in the EMBL-EBI European Nucleotide Archive
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Supplementary InformationPDF
Supplementary Figures and Tables
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Table S1. Read and Insertion Counts of S. Typhi Ty2 Transposon Library Sample...
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Table S2. Read and Insertion Counts of Input and Output Libraries from...
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Table S3. S. Typhi Genes Counter-selected in hu-SRC-SCID Mice 24 hpi, Related...
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Cell Host & Microbe
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Cell Host & Microbe
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Поле	Вредност
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Електронска пошта на одржувач
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