title: Oxidative stress defense mechanisms to counter iron-promoted DNA damage in Helicobacter pylori.
abstract: Iron, a key element in Fenton chemistry, causes oxygen-related toxicity to cells of most living organisms. Helicobacter pylori is a microaerophilic bacterium that infects human gastric mucosa and causes a series of gastric diseases. Exposure of H. pylori cells to air for 2 h elevated the level of free iron by about 4-fold as measured by electron paramagnetic resonance spectroscopy. H. pylori cells accumulated more free iron as they approached stationary phase growth, and they concomitantly suffered more DNA damage as indicated by DNA fragmentation analysis. Relationships between the intracellular free iron level, specific oxidative stress enzymes, and DNA damage were identified, and new roles for three oxidative stress-combating enzymes in H. pylori are proposed. Mutant cells defective in either catalase (KatA), in superoxide dismutase (SodB) or in alkyl hydroperoxide reductase (AhpC) were more sensitive to oxidative stress conditions; and they accumulated more free (toxic) iron; and they suffered more DNA fragmentation compared to wild type cells. A significant proportion of cells of sodB, ahpC, or katA mutant strains developed into the stress-induced coccoid form or lysed; they also contained significantly higher amounts of 8-oxo-guanine associated with their DNA, compared to wild type cells.
authors.affiliation: Department of Microbiology, University of Georgia, Athens, 30602, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.forename: Richard C
authors.initials: RC
authors.lastname: Conover
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Olczak
authors.forename: Praveen
authors.initials: P
authors.lastname: Alamuri
authors.forename: Michael K
authors.initials: MK
authors.lastname: Johnson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Maier
mesh_terms: D000388:Air; D001426:Bacterial Proteins / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D053938:DNA Fragmentation; D004578:Electron Spin Resonance Spectroscopy; D004586:Electrophoresis; D005456:Fluorescent Dyes / Q000494:pharmacology; D005609:Free Radicals; D005753:Gastric Mucosa / Q000382:microbiology; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D008280:Magnetics; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D009154:Mutation; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D054464:Peroxiredoxins; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D005456:Fluorescent Dyes; D005609:Free Radicals; D006151:Guanosine; C046215:8-hydroxyguanosine; C024829:8-hydroxyguanine; D006147:Guanine; D007501:Iron; D010544:Peroxidases; D054464:Peroxiredoxins; C508531:ahpC protein, Helicobacter pylori; D002374:Catalase; C090103:KATA protein, Bacillus subtilis; C508532:katA protein, Helicobacter pylori; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase; D010100:Oxygen