title: Ciprofloxacin provokes SOS-dependent changes in respiration and membrane potential and causes alterations in the redox status of Escherichia coli.
abstract: An in-depth understanding of the physiological response of bacteria to antibiotic-induced stress is needed for development of new approaches to combatting microbial infections. Fluoroquinolone ciprofloxacin causes phase alterations in Escherichia coli respiration and membrane potential that strongly depend on its concentration. Concentrations lower than the optimal bactericidal concentration (OBC) do not inhibit respiration during the first phase. A dose higher than the OBC provokes immediate SOS-independent inhibition of respiration and growth that can contribute to a decreased SOS response and lowered susceptibility to high concentrations of ciprofloxacin. Cells retain their metabolic activity, membrane potential and accelerated K+uptake and produce low levels of superoxide and H2O2during the first phase. The time before initiation of the second phase is inversely correlated with the ciprofloxacin concentration. The second phase is SOS-dependent and characterized by respiratory inhibition, membrane depolarization, K+and glutathione leakage and cessation of glucose consumption and may be considered as cell death. atpA, gshA and kefBkefC knockouts, which perturb fluxes of protons and K+, can modify the degree and duration of respiratory inhibition and potassium retention. Loss of K+efflux channels KefB and KefC enhances the susceptibility of E. coli to ciprofloxacin.
authors: Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. Electronic address: smirnova@iegm.ru.
authors: Galina V
authors: GV
authors: Smirnova
authors: Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. Electronic address: leksey333@yandex.ru.
authors: Aleksey V
authors: AV
authors: Tyulenev
authors: Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. Electronic address: muzyka@iegm.ru.
authors: Nadezda G
authors: NG
authors: Muzyka
authors: Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia. Electronic address: muxeu-mhz@mail.ru.
authors: Mikhail A
authors: MA
authors: Peters
authors: Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, ul. Goleva 13, Perm, 614081, Russia; Department of Chemistry and Biotechnology, Perm National Research Polytechnic University, Komsomolsky pr., 29, Perm, 614990, Russia. Electronic address: oktyabr@iegm.ru.
authors: Oleg N
authors: ON
authors: Oktyabrsky
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology*; D065609:Cytochrome P-450 CYP1A2 Inhibitors / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects*; D010084:Oxidation-Reduction; D013014:SOS Response, Genetics; D013312:Stress, Physiological; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin
keywords: Ciprofloxacin; Escherichia coli; Glutathione; K(+) efflux channels; Membrane potential; Respiration