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

31 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
Externally publishedYes


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