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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Bacterial Proteins / genetics
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Binding Sites / drug effects
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Binding Sites / genetics
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Drug Resistance, Microbial / genetics
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Extracellular Space / metabolism*
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Gene Expression Regulation, Bacterial / drug effects
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Gene Expression Regulation, Bacterial / genetics
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Iron / metabolism*
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Iron / pharmacology*
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Iron-Binding Proteins
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Phenotype
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Polymyxins / pharmacology
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Protein Structure, Tertiary / genetics
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Salmonella enterica / drug effects*
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Salmonella enterica / genetics
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Salmonella enterica / metabolism
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Signal Transduction / physiology*
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Transcription Factors / genetics
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Transcription, Genetic / genetics
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Transferrin-Binding Proteins
Substances
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Bacterial Proteins
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Carrier Proteins
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Iron-Binding Proteins
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PhoQ protein, Bacteria
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PmrB protein, bacteria
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Polymyxins
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Transcription Factors
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Transferrin-Binding Proteins
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pmrA protein, Bacteria
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PhoP protein, Bacteria
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Iron