Nalidixic Acid Resistance: A Second Genetic Character Involved in DNA Gyrase Activity

ATP-dependent DNA supercoiling catalyzed by Escherichia coli DNA gyrase was inhibited by oxolinic acid, a compound similar to but more potent than nalidixic acid and a known inhibitor of DNA replication in E. coli. The supercoiling activity of DNA gyrase purified from nalidixic acid-resistant mutant...

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Published in:Proceedings of the National Academy of Sciences - PNAS 1977-11, Vol.74 (11), p.4772-4776
Main Authors: Gellert, Martin, Mizuuchi, Kiyoshi, O'Dea, Mary H., Itoh, Tateo, Tomizawa, Jun-Ichi
Format: Article
Language:English
Subjects:
Bacteriophages
Biological Sciences: Biochemistry
Bromides
Cell free system
Centrifugation
DNA
DNA replication
DNA, Bacterial - metabolism
DNA, Superhelical - metabolism
Drug Resistance, Microbial
Enzymes
Escherichia coli - drug effects
Escherichia coli - enzymology
Escherichia coli - genetics
Genetic loci
Nalidixic Acid - pharmacology
Oxolinic Acid - pharmacology
Sodium
Sulfates
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Summary:ATP-dependent DNA supercoiling catalyzed by Escherichia coli DNA gyrase was inhibited by oxolinic acid, a compound similar to but more potent than nalidixic acid and a known inhibitor of DNA replication in E. coli. The supercoiling activity of DNA gyrase purified from nalidixic acid-resistant mutant (nalAR) bacteria was resistant to oxolinic acid. Thus, the nalA locus is responsible for a second component needed for DNA gyrase activity in addition to the component determined by the previously described locus for resistance to novobiocin and coumermycin (cou). Supercoiling of λ DNA in E. coli cells was likewise inhibited by oxolinic acid, but was resistant in the nalARmutant. The inhibition by oxolinic acid of colicin E1 plasmid DNA synthesis in a cell-free system was largely relieved by adding resistant DNA gyrase. In the absence of ATP, DNA gyrase preparations relaxed supercoiled DNA; this activity was also inhibited by oxolinic acid, but not by novobiocin. It appears that the oxolinic acid-sensitive component of DNA gyrase is involved in the nicking-closing activity required in the supercoiling reaction. In the presence of oxolinic acid, DNA gyrase forms a complex with DNA, which can be activated by later treatment with sodium dodecyl sulfate and a protease to produce double-strand breaks in the DNA. This process has some similarities to the known properties of relaxation complexes.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.74.11.4772