title: The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress.
abstract: Hydrogen peroxide pervades many natural environments, including the phagosomes that mediate cell-based immunity. Transcriptomic analysis showed that during protracted low-grade H(2)O(2) stress, Escherichia coli responds by activating both the OxyR defensive regulon and the Fur iron-starvation response. OxyR induced synthesis of two members of the nine-step heme biosynthetic pathway: ferrochelatase (HemH) and an isozyme of coproporphyrinogen III oxidase (HemF). Mutations that blocked either adaptation caused the accumulation of porphyrin intermediates, inadequate activation of heme enzymes, low catalase activity, defective clearance of H(2)O(2) and a failure to grow. Genetic analysis indicated that HemH induction is needed to compensate for iron sequestration by the mini-ferritin Dps. Dps activity protects DNA and proteins by limiting Fenton chemistry, but it interferes with the ability of HemH to acquire the iron that it needs to complete heme synthesis. HemF is a manganoprotein that displaces HemN, an iron-sulfur enzyme whose synthesis and/or stability is apparently problematic during H(2)O(2) stress. Thus, the primary responses to H(2)O(2), including the sequestration of iron, require compensatory adjustments in the mechanisms of iron-cofactor synthesis. The results support the growing evidence that oxidative stress is primarily an iron pathology.
authors: Department of Microbiology, University of Illinois, Urbana, IL, 61801, USA.
authors: Stefano
authors: S
authors: Mancini
authors: Department of Microbiology, University of Illinois, Urbana, IL, 61801, USA.
authors: James A
authors: JA
authors: Imlay
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics; D002374:Catalase / Q000378:metabolism*; D003304:Coproporphyrinogen Oxidase / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation; D004790:Enzyme Induction; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005294:Ferrochelatase / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D006418:Heme / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress; D011166:Porphyrins / Q000378:metabolism; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D011166:Porphyrins; D012097:Repressor Proteins; C499299:oxyR protein, E coli; D006418:Heme; D006861:Hydrogen Peroxide; D002374:Catalase; D003304:Coproporphyrinogen Oxidase; D005294:Ferrochelatase