Journal article
Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts
Proceedings of the National Academy of Sciences - PNAS, Vol.118(44), p.1
11/02/2021
DOI: 10.1073/pnas.2104073118
PMCID: PMC8612365
PMID: 34716262
Abstract
causes human plague and colonizes both a mammalian host and a flea vector during its transmission cycle. A key barrier to bacterial infection is the host's ability to actively sequester key biometals (e.g., iron, zinc, and manganese) required for bacterial growth. This is referred to as nutritional immunity. Mechanisms to overcome nutritional immunity are essential virulence factors for bacterial pathogens.
produces an iron-scavenging siderophore called yersiniabactin (Ybt) that is required to overcome iron-mediated nutritional immunity and cause lethal infection. Recently, Ybt has been shown to bind to zinc, and in the absence of the zinc transporter ZnuABC, Ybt improves
growth in zinc-limited medium. These data suggest that, in addition to iron acquisition, Ybt may also contribute to overcoming zinc-mediated nutritional immunity. To test this hypothesis, we used a mouse model defective in iron-mediated nutritional immunity to demonstrate that Ybt contributes to virulence in an iron-independent manner. Furthermore, using a combination of bacterial mutants and mice defective in zinc-mediated nutritional immunity, we identified calprotectin as the primary barrier for
to acquire zinc during infection and that
uses Ybt to compete with calprotectin for zinc. Finally, we discovered that
encounters zinc limitation within the flea midgut, and Ybt contributes to overcoming this limitation. Together, these results demonstrate that Ybt is a bona fide zinc acquisition mechanism used by
to surmount zinc limitation during the infection of both the mammalian and insect hosts.
Details
- Title: Subtitle
- Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts
- Creators
- Sarah L Price - University of LouisvilleViveka Vadyvaloo - Washington State UniversityJennifer K DeMarco - University of LouisvilleAmanda Brady - University of LouisvillePhoenix A Gray - University of LouisvilleThomas E Kehl-Fie - University of Illinois Urbana-ChampaignSylvie Garneau-Tsodikova - University of KentuckyRobert D Perry - University of KentuckyMatthew B Lawrenz - University of Louisville
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.118(44), p.1
- Publisher
- Proceedings of the National Academy of Sciences
- DOI
- 10.1073/pnas.2104073118
- PMID
- 34716262
- PMCID
- PMC8612365
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Grant note
- T32 AI132146 / NIAID NIH HHS R01 AI118880 / 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
- Language
- English
- Date published
- 11/02/2021
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618526702771
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