Genome-wide Analysis of Salmonella enterica serovar Typhi in Humanized Mice Reveals Key Virulence Features.
Amino Acids, Aromatic
/ biosynthesis
Animals
Bacterial Proteins
/ genetics
Bacterial Toxins
/ genetics
DNA-Activated Protein Kinase
/ genetics
DNA-Binding Proteins
/ genetics
Disease Models, Animal
Genome-Wide Association Study
/ methods
Genomic Islands
/ genetics
Humans
Interleukin Receptor Common gamma Subunit
/ genetics
Iron
/ metabolism
Lipopolysaccharides
/ metabolism
Membrane Proteins
/ genetics
Mice
Mice, Inbred NOD
Mice, Obese
Mice, SCID
Salmonella Infections
/ metabolism
Salmonella typhi
/ genetics
Siderophores
/ metabolism
THP-1 Cells
/ microbiology
Typhoid Fever
Virulence
/ genetics
PhoP
SPI-2
Salmonella Typhi
TraDIS
Vi
humanized mice
salmochelin
transposon library
typhoid toxin
virulence
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
11 09 2019
11 09 2019
Historique:
received:
22
05
2019
revised:
03
07
2019
accepted:
31
07
2019
pubmed:
27
8
2019
medline:
7
1
2020
entrez:
27
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31447308
pii: S1931-3128(19)30366-X
doi: 10.1016/j.chom.2019.08.001
pmc: PMC6742556
mid: NIHMS1537086
pii:
doi:
Substances chimiques
Amino Acids, Aromatic
0
Bacterial Proteins
0
Bacterial Toxins
0
CdtB protein, Salmonella typhimurium
0
DNA-Binding Proteins
0
Il2rg protein, mouse
0
Interleukin Receptor Common gamma Subunit
0
Lipopolysaccharides
0
Membrane Proteins
0
SPI-2 protein, Salmonella
0
Siderophores
0
Iron
E1UOL152H7
DNA-Activated Protein Kinase
EC 2.7.11.1
Prkdc protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
426-434.e6Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007509
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132963
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI112640
Pays : United States
Organisme : NIH HHS
ID : R24 OD018259
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI112640
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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