Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts

Sarah L Price; Viveka Vadyvaloo; Jennifer K DeMarco; Amanda Brady; Phoenix A Gray; Thomas E Kehl-Fie; Sylvie Garneau-Tsodikova; Robert D Perry; Matthew B Lawrenz

doi:10.1073/pnas.2104073118

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Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts

Journal article

Open access

Peer reviewed

Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts

Sarah L Price, Viveka Vadyvaloo, Jennifer K DeMarco, Amanda Brady, Phoenix A Gray, Thomas E Kehl-Fie, Sylvie Garneau-Tsodikova, Robert D Perry and Matthew B Lawrenz

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

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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.

Animals

ATP-Binding Cassette Transporters - metabolism

Female

Gene Expression - genetics

Gene Expression Regulation, Bacterial - genetics

Iron - metabolism

Male

Mice

Mice, 129 Strain

Mice, Inbred C57BL

Phenols - metabolism

Phenols - pharmacology

Plague - metabolism

Plague - microbiology

Siderophores - metabolism

Thiazoles - metabolism

Thiazoles - pharmacology

Virulence

Virulence Factors - metabolism

Yersinia pestis - pathogenicity

Zinc - metabolism

Details

Title: Subtitle: Yersiniabactin contributes to overcoming zinc restriction during Yersinia pestis infection of mammalian and insect hosts
Creators: Sarah L Price - University of Louisville
Viveka Vadyvaloo - Washington State University
Jennifer K DeMarco - University of Louisville
Amanda Brady - University of Louisville
Phoenix A Gray - University of Louisville
Thomas E Kehl-Fie - University of Illinois Urbana-Champaign
Sylvie Garneau-Tsodikova - University of Kentucky
Robert D Perry - University of Kentucky
Matthew B Lawrenz - University of Louisville
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.118(44), p.1
DOI: 10.1073/pnas.2104073118
PMID: 34716262
PMCID: PMC8612365
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: Proceedings of the National Academy of Sciences
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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