A signal transduction system that responds to extracellular iron.
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.
Wösten
M M
MM
Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kox
L F
LF
Chamnongpol
S
S
Soncini
F C
FC
Groisman
E A
EA
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
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