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. 1986 Apr;29(4):598–601. doi: 10.1128/aac.29.4.598

Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids.

M M Zweerink, A Edison
PMCID: PMC180449  PMID: 3010848

Abstract

The ability of norfloxacin, amifloxacin, cinoxacin, ciprofloxacin, flumequine, nalidixic acid, ofloxacin (OFL), oxolinic acid, perfloxacin, pipemidic acid, and rosoxacin to inhibit the in vitro supercoiling activity of Micrococcus luteus DNA gyrase was compared with the ability of each drug to inhibit the growth of the M. luteus strain from which the gyrase was purified. The potency of the quinolones as DNA gyrase inhibitors did not always correlate with antimicrobial potency. For example, OFL was a less potent inhibitor of gyrase than rosoxacin, yet the MIC of OFL was 16-fold lower than that of rosoxacin. Similarly, the MICs of norfloxacin and ciprofloxacin (the most potent of the antibiotics tested in these assays) were several hundredfold lower than the MIC of nalidixic acid (the least potent of these antibiotics), but the inhibition of purified gyrase by these two quinolones was only 8- to 16-fold lower than that of nalidixic acid. These results suggest that factors in addition to inhibition of gyrase supercoiling activity are important in determining the potency of these drugs. Further studies indicated that the uptake of norfloxacin, OFL, and amifloxacin by M. luteus cells may not account for the large differences in MICs observed for these drugs (MICs of 0.8, 2.0, and 128 micrograms/ml, respectively).

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Selected References

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  1. Bourguignon G. J., Levitt M., Sternglanz R. Studies on the mechanism of action of nalidixic acid. Antimicrob Agents Chemother. 1973 Oct;4(4):479–486. doi: 10.1128/aac.4.4.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crumplin G. C., Kenwright M., Hirst T. Investigations into the mechanism of action of the antibacterial agent norfloxacin. J Antimicrob Chemother. 1984 May;13 (Suppl B):9–23. doi: 10.1093/jac/13.suppl_b.9. [DOI] [PubMed] [Google Scholar]
  3. Deitz W. H., Cook T. M., Goss W. A. Mechanism of action of nalidixic acid on Escherichia coli. 3. Conditions required for lethality. J Bacteriol. 1966 Feb;91(2):768–773. doi: 10.1128/jb.91.2.768-773.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drlica K. Biology of bacterial deoxyribonucleic acid topoisomerases. Microbiol Rev. 1984 Dec;48(4):273–289. doi: 10.1128/mr.48.4.273-289.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Engle E. C., Manes S. H., Drlica K. Differential effects of antibiotics inhibiting gyrase. J Bacteriol. 1982 Jan;149(1):92–98. doi: 10.1128/jb.149.1.92-98.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gellert M., Mizuuchi K., O'Dea M. H., Itoh T., Tomizawa J. I. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4772–4776. doi: 10.1073/pnas.74.11.4772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gellert M., Mizuuchi K., O'Dea M. H., Nash H. A. DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3872–3876. doi: 10.1073/pnas.73.11.3872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hooper D. C., Wolfson J. S., McHugh G. L., Winters M. B., Swartz M. N. Effects of novobiocin, coumermycin A1, clorobiocin, and their analogs on Escherichia coli DNA gyrase and bacterial growth. Antimicrob Agents Chemother. 1982 Oct;22(4):662–671. doi: 10.1128/aac.22.4.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Högberg T., Khanna I., Drake S. D., Mitscher L. A., Shen L. L. Structure-activity relationships among DNA gyrase inhibitors. Synthesis and biological evaluation of 1,2-dihydro-4, 4-dimethyl-1-oxo-2-naphthalenecarboxylic acids as 1-carba bioisosteres of oxolinic acid. J Med Chem. 1984 Mar;27(3):306–310. doi: 10.1021/jm00369a013. [DOI] [PubMed] [Google Scholar]
  10. Ikeda H., Kawasaki I., Gellert M. Mechanism of illegitimate recombination: common sites for recombination and cleavage mediated by E. coli DNA gyrase. Mol Gen Genet. 1984;196(3):546–549. doi: 10.1007/BF00436208. [DOI] [PubMed] [Google Scholar]
  11. Klevan L., Wang J. C. Deoxyribonucleic acid gyrase-deoxyribonucleic acid complex containing 140 base pairs of deoxyribonucleic acid and an alpha 2 beta 2 protein core. Biochemistry. 1980 Nov 11;19(23):5229–5234. doi: 10.1021/bi00564a012. [DOI] [PubMed] [Google Scholar]
  12. Kreuzer K. N., Cozzarelli N. R. Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription, and bacteriophage growth. J Bacteriol. 1979 Nov;140(2):424–435. doi: 10.1128/jb.140.2.424-435.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liu L. F., Wang J. C. Micrococcus luteus DNA gyrase: active components and a model for its supercoiling of DNA. Proc Natl Acad Sci U S A. 1978 May;75(5):2098–2102. doi: 10.1073/pnas.75.5.2098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller R. V., Scurlock T. R. DNA gyrase (Topoisomerase II) from Pseudomonas aeruginosa. Biochem Biophys Res Commun. 1983 Jan 27;110(2):694–700. doi: 10.1016/0006-291x(83)91205-6. [DOI] [PubMed] [Google Scholar]
  15. Morrison A., Cozzarelli N. R. Site-specific cleavage of DNA by E. coli DNA gyrase. Cell. 1979 May;17(1):175–184. doi: 10.1016/0092-8674(79)90305-2. [DOI] [PubMed] [Google Scholar]
  16. O'Connor M. B., Malamy M. H. Mapping of DNA gyrase cleavage sites in vivo oxolinic acid induced cleavages in plasmid pBR322. J Mol Biol. 1985 Feb 20;181(4):545–550. doi: 10.1016/0022-2836(85)90426-7. [DOI] [PubMed] [Google Scholar]
  17. Pulleyblank D. E., Shure M., Vinograd J. The quantitation of fluorescence by photography. Nucleic Acids Res. 1977;4(5):1409–1418. doi: 10.1093/nar/4.5.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shen L. L., Pernet A. G. Mechanism of inhibition of DNA gyrase by analogues of nalidixic acid: the target of the drugs is DNA. Proc Natl Acad Sci U S A. 1985 Jan;82(2):307–311. doi: 10.1073/pnas.82.2.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Snyder M., Drlica K. DNA gyrase on the bacterial chromosome: DNA cleavage induced by oxolinic acid. J Mol Biol. 1979 Jun 25;131(2):287–302. doi: 10.1016/0022-2836(79)90077-9. [DOI] [PubMed] [Google Scholar]
  20. Sugino A., Peebles C. L., Kreuzer K. N., Cozzarelli N. R. Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4767–4771. doi: 10.1073/pnas.74.11.4767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Van Caekenberghe D. L., Pattyn S. R. In vitro activity of ciprofloxacin compared with those of other new fluorinated piperazinyl-substituted quinoline derivatives. Antimicrob Agents Chemother. 1984 Apr;25(4):518–521. doi: 10.1128/aac.25.4.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yamagishi J., Furutani Y., Inoue S., Ohue T., Nakamura S., Shimizu M. New nalidixic acid resistance mutations related to deoxyribonucleic acid gyrase activity. J Bacteriol. 1981 Nov;148(2):450–458. doi: 10.1128/jb.148.2.450-458.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

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