title: [Role of reactive oxygen species in the bactericidal action of quinolones--inhibitors of DNA gyrase].
abstract: Quinolone antibiotics inhibit DNA gyrase, but the induced degradation of chromosomal DNA is determined by a complex process of joint action quinolones and hydroxyl radical OH'. To quantify the level of stress responses and their time dependence in bacterial cells the induced specific lux-biosensors--the bacterium Escherichia coli, containing hybrid plasmids pColD'::lux; pSoxS'::lux; pKatG'::lux were used in this study. It is shown that quinolones (nalidixic acid, norfloxacin) induce SOS-response and oxidative stress with the formation of superoxide anion O2(-) in E. coli cells. The main parameters of SOS-response and oxidative stress, which depend on the quinolone concentration, are determined. Formation of superoxide anion O2(-) occurs almost simultaneously with the SOS-response. The mutant strain of E. coli sodA sodB, which do not contain active forms of superoxide dismutases SodA and SodB, is characterized by an increased resistance to quinolones as compared to the wild type cells. At high concentrations of quinolones (nalidixic acid-->20 μg/mL; norfloxacin-->500 ng/mL) their bactericidal effect is partially caused by conversion of the superoxide anion to hydrogen peroxide H2O2, conducted by superoxide dismutases SodA and SodB, which is followed by the Fenton reaction and the formation of toxic hydroxyl radical OH'. At low concentrations of quinolones (nalidixic acid--<20 μg/mL; norfloxacin--<500 ng/mL), the role of active oxygen species in the antimicrobial effect is practically nonexistent.
authors.forename: V Iu
authors.initials: VIu
authors.lastname: Kotova
authors.forename: A S
authors.initials: AS
authors.lastname: Mironov
authors.forename: G B
authors.initials: GB
authors.lastname: Zavigel'skiĭ
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D027081:DNA Gyrase / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D049408:Luminescent Agents / Q000737:chemistry / Q000378:metabolism; D009268:Nalidixic Acid / Q000494:pharmacology*; D009643:Norfloxacin / Q000494:pharmacology*; D018384:Oxidative Stress; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D013014:SOS Response, Genetics / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D049408:Luminescent Agents; D015534:Trans-Activators; D013481:Superoxides; C070725:SoxS protein, E coli; D009268:Nalidixic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; C051253:katG protein, E coli; C095500:SodA protein, Bacteria; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase; C526462:GDP-4-keto-6-deoxymannose-3-dehydratase, E coli; D006836:Hydro-Lyases; D027081:DNA Gyrase; D009643:Norfloxacin