title: A signal transduction system that responds to extracellular iron.
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.
authors.affiliation: Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Wösten
authors.forename: L F
authors.initials: LF
authors.lastname: Kox
authors.forename: S
authors.initials: S
authors.lastname: Chamnongpol
authors.forename: F C
authors.initials: FC
authors.lastname: Soncini
authors.forename: E A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004352:Drug Resistance, Microbial / Q000235:genetics; D005110:Extracellular Space / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology*; D033862:Iron-Binding Proteins; D010641:Phenotype; D011113:Polymyxins / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000235:genetics; D019779:Salmonella enterica / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D033863:Transferrin-Binding Proteins
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D033862:Iron-Binding Proteins; C079792:PhoQ protein, Bacteria; C409039:PmrB protein, bacteria; D011113:Polymyxins; D014157:Transcription Factors; D033863:Transferrin-Binding Proteins; C081902:pmrA protein, Bacteria; C061064:PhoP protein, Bacteria; D007501:Iron