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. Chazin; Sylvie Garneau-Tsodikova; Matthew B. Lawrenz; Robert D. Perry; Sean Paul Nuccio; Pieter C. Dorrestein; Manuela Raffatellu

doi:10.1038/s41467-021-27297-2

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 journal › Article › peer-review

42 Scopus citations

Abstract

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 language	English
Article number	7016
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27297-2
State	Published - Dec 2021

Bibliographical note

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

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Behnsen, J., Zhi, H., Aron, A. T., Subramanian, V., Santus, W., Lee, M. H., Gerner, R. R., Petras, D., Liu, J. Z., Green, K. D., Price, S. L., Camacho, J., Hillman, H., Tjokrosurjo, J., Montaldo, N. P., Hoover, E. M., Treacy-Abarca, S., Gilston, B. A., Skaar, E. P., ... Raffatellu, M. (2021). Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut. Nature Communications, 12(1), Article 7016. https://doi.org/10.1038/s41467-021-27297-2

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title = "Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut",

abstract = "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{\textquoteright}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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41467-021-27297-2",

language = "English",

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Behnsen, J, Zhi, H, Aron, AT, Subramanian, V, Santus, W, Lee, MH, Gerner, RR, Petras, D, Liu, JZ, Green, KD, Price, SL, Camacho, J, Hillman, H, Tjokrosurjo, J, Montaldo, NP, Hoover, EM, Treacy-Abarca, S, Gilston, BA, Skaar, EP, Chazin, WJ, Garneau-Tsodikova, S, Lawrenz, MB, Perry, RD, Nuccio, SP, Dorrestein, PC & Raffatellu, M 2021, 'Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut', Nature Communications, vol. 12, no. 1, 7016. https://doi.org/10.1038/s41467-021-27297-2

TY - JOUR

T1 - Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut

AU - Behnsen, Judith

AU - Zhi, Hui

AU - Aron, Allegra T.

AU - Subramanian, Vivekanandan

AU - Santus, William

AU - Lee, Michael H.

AU - Gerner, Romana R.

AU - Petras, Daniel

AU - Liu, Janet Z.

AU - Green, Keith D.

AU - Price, Sarah L.

AU - Camacho, Jose

AU - Hillman, Hannah

AU - Tjokrosurjo, Joshua

AU - Montaldo, Nicola P.

AU - Hoover, Evelyn M.

AU - Treacy-Abarca, Sean

AU - Gilston, Benjamin A.

AU - Skaar, Eric P.

AU - Chazin, Walter J.

AU - Garneau-Tsodikova, Sylvie

AU - Lawrenz, Matthew B.

AU - Perry, Robert D.

AU - Nuccio, Sean Paul

AU - Dorrestein, Pieter C.

AU - Raffatellu, Manuela

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-021-27297-2

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SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7016

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

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