Streptonigrin toxicity in Escherichia coli: oxygen dependence and the role of the intracellular oxidation--reduction state.
The bacterial physiology of streptonigrin toxicity was further investigated. An optimal oxygen concentration for toxicity was inferred from data showing that streptonigrin at 5 micrograms/mL was rapidly lethal to aerobic cultures of Escherichia coli K12JF361, but was without effect on anaerobic cultures and was bacteriostatic to cultures inhibited in 5 atm of oxygen plus 1 atm of air (5 atm O2 plus air) (1 atm = 101.325 kPa). Escherichia coli were protected from a potentially lethal concentration of streptonigrin during anaerobic incubation, whether previously grown anaerobically, aerobically, or in 5 atm O2 plus air. Superoxide dismutase activity increased with increasing oxygen tension in the medium, but was not significantly changed by a lethal concentration of streptonigrin. Although the superoxide dismutase activity was four times greater in E. coli grown in 5 atm O2 plus air than those grown in air alone, the aerobic survival in 5 micrograms/mL streptonigrin was identical, which suggested that superoxide dismutase was not rate limiting for toxicity. Escherichia coli K12 strains deficient in glutathione (KMBL54-129, AB1157-821, and AB1157-830) were protected from streptonigrin poisoning. Dithiothreotol (5.0 mM), diamide (1 mM), methyl viologen (1 mM), and cyanide (10 mM) protected aerobic E. coli from 5 micrograms/mL streptonigrin. These data are also consistent with a model of in vivo streptonigrin toxicity that requires a favorable intracellular oxidation--reduction state and an optimal concentration of molecular oxygen.
D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D005978:Glutathione / Q000502:physiology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000502:physiology*; D013308:Streptonigrin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D004269:DNA, Bacterial; D013308:Streptonigrin; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen