Roles of the glutathione- and thioredoxin-dependent systems in the Escherichia coli responses to ciprofloxacin and ampicillin.
Recently, it was proposed that some antibiotics stimulate the production of reactive oxygen species (ROS), which contribute to cell death. Later, other research groups have provided arguments against ROS-mediated killing of bacteria by antibiotics. At present, there remain a number of unanswered questions in understanding of the role of ROS in killing by antibiotics. Mutants of Escherichia coli in components of the thioredoxin and glutaredoxin redox pathways used in this study possess a great variability in antioxidant activity, and they therefore are a useful model for the investigation of the role of oxidative stress in bactericidal effect of antibiotics. Statistical analysis did not reveal a significant correlation between the susceptibility of the mutants to ciprofloxacin and ampicillin and their resistance to peroxide stress. However, we found strong reverse correlations between the bactericidal activity of antibiotics and the specific growth rate of these mutants at the moment of drug addition. Supplements changing the level of intra- and extracellular glutathione considerably affected E. coli susceptibility to ciprofloxacin and ampicillin. The effect of GSH precursors on bactericidal activity of antibiotics was also observed in gshA mutants.
Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Golev Street 13, Perm, Russia, 614081.
Galina
G
Smirnova
Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Golev Street 13, Perm, Russia, 614081.
Nadezda
N
Muzyka
Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Golev Street 13, Perm, Russia, 614081.|Department of Chemistry and Biotechnology, Perm National Research Polytechnic University, Komsomolsky pr., 29, Perm, Russia, 614990.
Elena
E
Lepekhina
Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Golev Street 13, Perm, Russia, 614081. oktyabr@iegm.ru.|Department of Chemistry and Biotechnology, Perm National Research Polytechnic University, Komsomolsky pr., 29, Perm, Russia, 614990. oktyabr@iegm.ru.
Oleg
O
Oktyabrsky
D000667:Ampicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000502:physiology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D054477:Glutaredoxins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000502:physiology*
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D001426:Bacterial Proteins; C516005:GLRX protein, human; D054477:Glutaredoxins; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D002939:Ciprofloxacin; D000667:Ampicillin; D005978:Glutathione
Antibiotics; Escherichia coli; Glutathione; Oxidative stress