Submicromolar hydrogen peroxide disrupts the ability of Fur protein to control free-iron levels in Escherichia coli.
In aerobic environments, mutants of Escherichia coli that lack peroxidase and catalase activities (Hpx(-)) accumulate submicromolar concentrations of intracellular H(2)O(2). We observed that in defined medium these strains constitutively expressed members of the Fur regulon. Iron-import proteins, which Fur normally represses, were fully induced. H(2)O(2) may antagonize Fur function by oxidizing the Fur:Fe(2+) complex and inactivating its repressor function. This is a potential problem, as in iron-rich environments excessive iron uptake would endanger H(2)O(2)-stressed cells by accelerating hydroxyl-radical production through the Fenton reaction. However, the OxyR H(2)O(2)-response system restored Fur repression in iron-replete Luria-Bertani medium by upregulating the synthesis of Fur protein. Indeed, when the OxyR binding site upstream of fur was disrupted, Hpx(-) mutants failed to repress transporter synthesis, and they exhibited high levels of intracellular free iron. Mutagenesis and bacteriostasis resulted. These defects were eliminated by mutations or chelators that slowed iron import, confirming that dysregulation of iron uptake was the root problem. Thus, aerobic organisms must grapple with a conundrum: how to monitor iron levels in oxidizing environments that might perturb the valence of the analyte. The induction of Fur synthesis by the OxyR response comprises one evolutionary solution to that problem.
Varghese
Shery
S
Department of Microbiology, University of Illinois, Urbana, IL 61801, USA.
Wu
Amy
A
Park
Sunny
S
Imlay
Karin R C
KR
Imlay
James A
JA
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D016296:Mutagenesis; D009154:Mutation; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D018085:Regulon / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C068477:ferric uptake regulating proteins, bacterial; C499299:oxyR protein, E coli; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; D010544:Peroxidases