Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence.
Amino Acid Sequence
Animals
Antitoxins
/ immunology
Bacterial Proteins
/ genetics
Bacterial Toxins
/ genetics
Cross Reactions
/ immunology
Endotoxins
/ genetics
Female
HEK293 Cells
Host Adaptation
/ drug effects
Humans
Male
Mice, Knockout
Polysaccharides
/ biosynthesis
Salmonella
Salmonella typhi
/ immunology
Typhoid Fever
/ microbiology
Typhoid-Paratyphoid Vaccines
/ immunology
Virulence
Salmonella
bacterial AB toxins
cross-reactive protection or immunity
glycan expression
glycans
host adaptations
receptor-binding
structure of protein toxins
typhoid fever
typhoid toxin
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
10 06 2020
10 06 2020
Historique:
received:
26
06
2019
revised:
18
02
2020
accepted:
03
04
2020
pubmed:
13
5
2020
medline:
20
1
2021
entrez:
13
5
2020
Statut:
ppublish
Résumé
Typhoidal and non-typhoidal Salmonelleae (NTS) cause typhoid fever and gastroenteritis, respectively, in humans. Salmonella typhoid toxin contributes to typhoid disease progression and chronic infection, but little is known about the role of its NTS ortholog. We found that typhoid toxin and its NTS ortholog induce different clinical presentations. The PltB subunit of each toxin exhibits different glycan-binding preferences that correlate with glycan expression profiles of host cells targeted by each bacterium at the primary infection or intoxication sites. Through co-crystal structures of PltB subunits bound to specific glycan receptor moieties, we show that they induce markedly different glycan-binding preferences and virulence outcomes. Furthermore, immunization with the NTS S. Javiana or its toxin offers cross-reactive protection against lethal-dose typhoid toxin challenge. Cumulatively, these results offer insights into the evolution of host adaptations in Salmonella AB toxins, their cell and tissue tropisms, and the design for improved typhoid vaccines and therapeutics.
Identifiants
pubmed: 32396840
pii: S1931-3128(20)30232-8
doi: 10.1016/j.chom.2020.04.005
pmc: PMC7292776
mid: NIHMS1585633
pii:
doi:
Substances chimiques
Antitoxins
0
Bacterial Proteins
0
Bacterial Toxins
0
Endotoxins
0
PltB protein, Salmonella typhimurium
0
Polysaccharides
0
Typhoid-Paratyphoid Vaccines
0
salmonella toxin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
937-949.e6Subventions
Organisme : NIAID NIH HHS
ID : R01 AI141514
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI139625
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137345
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114730
Pays : United States
Organisme : NIAID NIH HHS
ID : R03 AI135767
Pays : United States
Organisme : NIH HHS
ID : S10 OD012289
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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