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

Nat Commun. 2021 Dec 1;12(1):7016. doi: 10.1038/s41467-021-27297-2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters
  • Animals
  • Bacterial Proteins / metabolism
  • Carrier Proteins
  • Colon / microbiology
  • Colon / pathology
  • Enterobacteriaceae / metabolism*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins
  • Female
  • Leukocyte L1 Antigen Complex
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Phenols
  • Salmonella typhi
  • Siderophores / metabolism*
  • Thiazoles
  • Zinc / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Carrier Proteins
  • Escherichia coli Proteins
  • Leukocyte L1 Antigen Complex
  • Membrane Transport Proteins
  • Phenols
  • Siderophores
  • Thiazoles
  • ZnuA protein, E coli
  • yersiniabactin
  • zinc-binding protein
  • Zinc