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

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Yersinia pestis 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. Y. pestis 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 Y. pestis 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 Y. pestis to acquire zinc during infection and that Y. pestis uses Ybt to compete with calprotectin for zinc. Finally, we discovered that Y. pestis 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 Y. pestis to surmount zinc limitation during the infection of both the mammalian and insect hosts.

Original languageEnglish
Article numbere2104073118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number44
DOIs
StatePublished - Nov 2 2021

Bibliographical note

Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.

Keywords

  • Insect vectors
  • Nutritional immunity
  • Siderophores
  • Yersinia pestis and plague
  • Zinc acquisition

ASJC Scopus subject areas

  • General

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