Droplet Tn-Seq identifies the primary secretion mechanism for yersiniabactin in Yersinia pestis.
Yersinia pestis
drug efflux systems
plague
siderophores
transposon mutagenesis
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
09 10 2023
09 10 2023
Historique:
revised:
07
07
2023
received:
20
04
2023
accepted:
14
07
2023
pmc-release:
28
07
2024
medline:
10
10
2023
pubmed:
28
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
Nutritional immunity includes sequestration of transition metals from invading pathogens. Yersinia pestis overcomes nutritional immunity by secreting yersiniabactin to acquire iron and zinc during infection. While the mechanisms for yersiniabactin synthesis and import are well-defined, those responsible for yersiniabactin secretion are unknown. Identification of this mechanism has been difficult because conventional mutagenesis approaches are unable to inhibit trans-complementation by secreted factors between mutants. To overcome this obstacle, we utilized a technique called droplet Tn-seq (dTn-seq), which uses microfluidics to isolate individual transposon mutants in oil droplets, eliminating trans-complementation between bacteria. Using this approach, we first demonstrated the applicability of dTn-seq to identify genes with secreted functions. We then applied dTn-seq to identify an AcrAB efflux system as required for growth in metal-limited conditions. Finally, we showed this efflux system is the primary yersiniabactin secretion mechanism and required for virulence during bubonic and pneumonic plague. Together, these studies have revealed the yersiniabactin secretion mechanism that has eluded researchers for over 30 years and identified a potential therapeutic target for bacteria that use yersiniabactin for metal acquisition.
Identifiants
pubmed: 37501563
doi: 10.15252/embr.202357369
pmc: PMC10561177
doi:
Substances chimiques
yersiniabactin
0
Phenols
0
Thiazoles
0
Metals
0
Bacterial Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e57369Subventions
Organisme : NIAID NIH HHS
ID : U01 AI124302
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI147404
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148241
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135225
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155611
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI148470
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI132146
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI110724
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM125504
Pays : United States
Informations de copyright
© 2023 The Authors.
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