A Signal Transduction System That Responds to Extracellular Iron

Cell. 2000 Sep 29;103(1):113-25. doi: 10.1016/s0092-8674(00)00092-1.

Abstract

Iron is essential for all organisms but can be toxic in excess. Iron homeostasis is typically regulated by cytoplasmic iron binding proteins, but here we describe a signal transduction system (PmrA/PmrB) that responds to extracytoplasmic ferric iron. Iron promoted transcription of PmrA-activated genes and resistance to the antibiotic polymyxin in Salmonella. The PmrB protein bound iron via its periplasmic domain which harbors two copies of the sequence ExxE, a motif present in the Saccharomyces FTR1 iron transporter and in mammalian ferritin light chain. A pmrA mutant was hypersensitive to killing by iron but displayed wild-type resistance to a variety of oxidants, suggesting PmrA/PmrB controls a novel pathway mediating the avoidance of iron toxicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins / genetics
  • Binding Sites / drug effects
  • Binding Sites / genetics
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Drug Resistance, Microbial / genetics
  • Extracellular Space / metabolism*
  • Gene Expression Regulation, Bacterial / drug effects
  • Gene Expression Regulation, Bacterial / genetics
  • Iron / metabolism*
  • Iron / pharmacology*
  • Iron-Binding Proteins
  • Phenotype
  • Polymyxins / pharmacology
  • Protein Structure, Tertiary / genetics
  • Salmonella enterica / drug effects*
  • Salmonella enterica / genetics
  • Salmonella enterica / metabolism
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Transcription, Genetic / genetics
  • Transferrin-Binding Proteins

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Iron-Binding Proteins
  • PhoQ protein, Bacteria
  • PmrB protein, bacteria
  • Polymyxins
  • Transcription Factors
  • Transferrin-Binding Proteins
  • pmrA protein, Bacteria
  • PhoP protein, Bacteria
  • Iron