Journal article
Droplet Tn-Seq identifies the primary secretion mechanism for yersiniabactin in Yersinia pestis
EMBO reports, Vol.24(10), pp.e57369-e57369
10/09/2023
DOI: 10.15252/embr.202357369
PMCID: PMC10561177
PMID: 37501563
Abstract
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.
Details
- Title: Subtitle
- Droplet Tn-Seq identifies the primary secretion mechanism for yersiniabactin in Yersinia pestis
- Creators
- Sarah L Price - University of LouisvilleDerek Thibault - Boston CollegeTaylor M Garrison - University of LouisvilleAmanda Brady - University of LouisvilleHaixun Guo - University of LouisvilleThomas E Kehl-Fie - University of Illinois Urbana-ChampaignSylvie Garneau-Tsodikova - University of KentuckyRobert D Perry - University of KentuckyTim van Opijnen - Broad InstituteMatthew B Lawrenz - University of Louisville
- Resource Type
- Journal article
- Publication Details
- EMBO reports, Vol.24(10), pp.e57369-e57369
- Publisher
- Springer Science and Business Media LLC
- DOI
- 10.15252/embr.202357369
- PMID
- 37501563
- PMCID
- PMC10561177
- ISSN
- 1469-221X
- eISSN
- 1469-3178
- Grant note
- R01 AI148470 / NIAID NIH HHS R01 AI110724 / NIAID NIH HHS T32 AI132146 / NIAID NIH HHS P20 GM125504 / NIGMS NIH HHS R01 AI148241 / NIAID NIH HHS R21 AI135225 / NIAID NIH HHS R01 AI155611 / NIAID NIH HHS F31 AI147404 / NIAID NIH HHS U01 AI124302 / NIAID NIH HHS
- Language
- English
- Date published
- 10/09/2023
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618636502771
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