Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut

Judith Behnsen, Hui Zhi, Allegra T. Aron, Vivekanandan Subramanian, William Santus, Michael H. Lee, Romana R. Gerner, Daniel Petras, Janet Z. Liu, Keith D. Green, Sarah L. Price, Jose Camacho, Hannah Hillman, Joshua Tjokrosurjo, Nicola P. Montaldo, Evelyn M. Hoover, Sean Treacy-Abarca, Benjamin A. Gilston, Eric P. Skaar, Walter J. ChazinSylvie Garneau-Tsodikova, Matthew B. Lawrenz, Robert D. Perry, Sean Paul Nuccio, Pieter C. Dorrestein, Manuela Raffatellu

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or “Nissle”) exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the pH increases. Thus, our results indicate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to commensal and pathogenic Enterobacteriaceae.

Original languageEnglish
Article number7016
JournalNature Communications
Issue number1
StatePublished - Dec 2021

Bibliographical note

Funding Information:
Work in MR lab is supported by Public Health Service Grants AI126277, AI114625, and AI145325, by the Chiba University-UCSD Center for Mucosal Immunology, Allergy, and Vaccines, and by the UCSD Department of Pediatrics. M.R. also holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. MHL was partly supported by NIH training grant T32 DK007202. R.R.G. was partly supported by a fellowship from the Max Kade Foundation and by a fellowship from the Crohns and Colitis Foundation. Work in the JB lab is supported by NIH grants AI143641, DK098170, and University of Illinois at Chicago Institutional startup funds. Work in the EPS and WJC laboratories is supported by Public Health Service Grant AI101171. M.B.L. was supported by NIH grants P20GM125504, R21AI119557, and in part by a grant from the Jewish Heritage Fund for Excellence Research Enhancement Grant Program at the University of Louisville School of Medicine. S.L.P. was supported by T32AI132146 and F31AI147404. P.C.D. acknowledges the support by NIH for this work under 5U01AI124316, P41GM103484, GMS10RR029121, and Gordon and Betty Moore Foundation for the development of the computational infrastructure to study symbiotic interactions. The authors would like to thank Joe Burlison in the Medicinal Chemistry Lab at the James Graham Brown Cancer Center at the University of Louisville for help with Ybt purification and the UK PharmNMR Center in the College of Pharmacy at the University of Kentucky for NMR support. Slide scanning of histological sections was done at the UCSD School of Medicine Microscopy Core Facility, which is supported by the grant P30 NS047101. Sequencing was performed at the DNA Services (DNAS) facility within the Research Resources Center (RRC) at the University of Illinois at Chicago (UIC). Bioinformatics analysis in the project described was performed by the UIC Research Informatics Core, supported in part by NCATS through Grant UL1TR002003. Some schemes were created with

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • General
  • Physics and Astronomy (all)


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