YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner

Nucleic Acids Res. 2020 Sep 25;48(17):9571-9588. doi: 10.1093/nar/gkaa696.

Abstract

Iron is essential for all bacteria. In most bacteria, intracellular iron homeostasis is tightly regulated by the ferric uptake regulator Fur. However, how Fur activates the iron-uptake system during iron deficiency is not fully elucidated. In this study, we found that YdiV, the flagella gene inhibitor, is involved in iron homeostasis in Escherichia coli. Iron deficiency triggers overexpression of YdiV. High levels of YdiV then transforms Fur into a novel form which does not bind DNA in a peptidyl-prolyl cis-trans isomerase SlyD dependent manner. Thus, the cooperation of YdiV, SlyD and Fur activates the gene expression of iron-uptake systems under conditions of iron deficiency. Bacterial invasion assays also demonstrated that both ydiV and slyD are necessary for the survival and growth of uropathogenic E. coli in bladder epithelial cells. This reveals a mechanism where YdiV not only represses flagella expression to make E. coli invisible to the host immune system, but it also promotes iron acquisition to help E. coli overcome host nutritional immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA, Bacterial / metabolism
  • Epithelial Cells / microbiology
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Expression Regulation, Bacterial
  • Homeostasis
  • Humans
  • Iron / metabolism*
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Protein Conformation
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Urinary Bladder / microbiology
  • Uropathogenic Escherichia coli / genetics
  • Uropathogenic Escherichia coli / growth & development
  • Uropathogenic Escherichia coli / metabolism
  • Uropathogenic Escherichia coli / pathogenicity*

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Repressor Proteins
  • SlyD protein, E coli
  • YdiV protein, E coli
  • ferric uptake regulating proteins, bacterial
  • Iron
  • Peptidylprolyl Isomerase