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Cyanide enhances hydrogen peroxide toxicity by recruiting endogenous iron to trigger catastrophic chromosomal fragmentation
Author(s) -
Mahaseth Tulip,
Kuzminov Andrei
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12938
Subject(s) - hydrogen peroxide , ferritin , intracellular , cyanide , toxicity , biology , dna damage , hydrogen cyanide , escherichia coli , reactive oxygen species , biochemistry , microbiology and biotechnology , chemistry , dna , inorganic chemistry , organic chemistry , gene
Summary Hydrogen peroxide ( HP ) or cyanide ( CN ) are bacteriostatic at low‐millimolar concentrations for growing E scherichia coli , whereas CN + HP mixture is strongly bactericidal. We show that this synergistic toxicity is associated with catastrophic chromosomal fragmentation. Since CN alone does not kill at any concentration, while HP alone kills at 20 mM, CN must potentiate HP poisoning. The CN + HP killing is blocked by iron chelators, suggesting Fenton's reaction. Indeed, we show that CN enhances plasmid DNA relaxation due to Fenton's reaction in vitro . However, mutants with elevated iron or HP pools are not acutely sensitive to HP ‐alone treatment, suggesting that, in addition, in vivo CN recruits iron from intracellular depots. We found that part of the CN ‐recruited iron pool is managed by ferritin and Dps : ferritin releases iron on cue from CN , while Dps sequesters it, quelling F enton's reaction. We propose that disrupting intracellular iron trafficking is a common strategy employed by the immune system to kill microbes.