Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1988 Aug;32(8):1192–1195. doi: 10.1128/aac.32.8.1192

DNA gyrase of Staphylococcus aureus and inhibitory effect of quinolones on its activity.

M Takahata 1, T Nishino 1
PMCID: PMC172375  PMID: 2847648

Abstract

DNA gyrase from Staphylococcus aureus FDA 209P was partially purified by lysostaphin treatment, saturation with ammonium sulfate, and affinity chromatography on heparin-Sepharose and with a concentrator (Centricon 30). It was found to consist of two subunits: alpha and beta. The ability of new quinolone antibacterial agents such as norfloxacin, ofloxacin, and ciprofloxacin to inhibit DNA gyrase activity and cell growth was investigated. The inhibitory effects of the new quinolones against the activity of S. aureus DNA gyrase were in parallel with their antibacterial activities. The 50% inhibitory doses of norfloxacin, ofloxacin, and ciplofloxacin were 0.34, 0.31, and 0.24 micrograms/ml, respectively, while the 50% inhibitory doses of nalidixic acid and cinoxacin, which were less active against S. aureus FDA 209P, were 100 micrograms/ml or more.

Full text

PDF
1194

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chin N. X., Brittain D. C., Neu H. C. In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone. Antimicrob Agents Chemother. 1986 Apr;29(4):675–680. doi: 10.1128/aac.29.4.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Domagala J. M., Hanna L. D., Heifetz C. L., Hutt M. P., Mich T. F., Sanchez J. P., Solomon M. New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay. J Med Chem. 1986 Mar;29(3):394–404. doi: 10.1021/jm00153a015. [DOI] [PubMed] [Google Scholar]
  3. Drapeau G. R., Boily Y., Houmard J. Purification and properties of an extracellular protease of Staphylococcus aureus. J Biol Chem. 1972 Oct 25;247(20):6720–6726. [PubMed] [Google Scholar]
  4. Fu K. P., Grace M. E., McCloud S. J., Gregory F. J., Hung P. P. Discrepancy between the antibacterial activities and the inhibitory effects on Micrococcus luteus DNA gyrase of 13 quinolones. Chemotherapy. 1986;32(6):494–498. doi: 10.1159/000238458. [DOI] [PubMed] [Google Scholar]
  5. Gellert M., Fisher L. M., O'Dea M. H. DNA gyrase: purification and catalytic properties of a fragment of gyrase B protein. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6289–6293. doi: 10.1073/pnas.76.12.6289. [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. Hooper D. C., Wolfson J. S., Souza K. S., Tung C., McHugh G. L., Swartz M. N. Genetic and biochemical characterization of norfloxacin resistance in Escherichia coli. Antimicrob Agents Chemother. 1986 Apr;29(4):639–644. doi: 10.1128/aac.29.4.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ito A., Hirai K., Inoue M., Koga H., Suzue S., Irikura T., Mitsuhashi S. In vitro antibacterial activity of AM-715, a new nalidixic acid analog. Antimicrob Agents Chemother. 1980 Feb;17(2):103–108. doi: 10.1128/aac.17.2.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Muytjens H. L., van der Ros-van de Repe J., van Veldhuizen G. Comparative activities of ciprofloxacin (Bay o 9867), norfloxacin, pipemidic acid, and nalidixic acid. Antimicrob Agents Chemother. 1983 Aug;24(2):302–304. doi: 10.1128/aac.24.2.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Orr E., Staudenbauer W. L. Bacillus subtilis DNA gyrase: purification of subunits and reconstitution of supercoiling activity. J Bacteriol. 1982 Jul;151(1):524–527. doi: 10.1128/jb.151.1.524-527.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rydén A. C., Rydén L., Philipson L. Isolation and properties of a staphylococcal protease, preferentially cleaving glutamoyl-peptide bonds. Eur J Biochem. 1974 May 2;44(1):105–114. doi: 10.1111/j.1432-1033.1974.tb03462.x. [DOI] [PubMed] [Google Scholar]
  17. Sato K., Inoue Y., Fujii T., Aoyama H., Inoue M., Mitsuhashi S. Purification and properties of DNA gyrase from a fluoroquinolone-resistant strain of Escherichia coli. Antimicrob Agents Chemother. 1986 Nov;30(5):777–780. doi: 10.1128/aac.30.5.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sato K., Matsuura Y., Inoue M., Une T., Osada Y., Ogawa H., Mitsuhashi S. In vitro and in vivo activity of DL-8280, a new oxazine derivative. Antimicrob Agents Chemother. 1982 Oct;22(4):548–553. doi: 10.1128/aac.22.4.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Staudenbauer W. L., Orr E. DNA gyrase: affinity chromatography on novobiocin-Sepharose and catalytic properties. Nucleic Acids Res. 1981 Aug 11;9(15):3589–3603. doi: 10.1093/nar/9.15.3589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sugino A., Bott K. F. Bacillus subtilis deoxyribonucleic acid gyrase. J Bacteriol. 1980 Mar;141(3):1331–1339. doi: 10.1128/jb.141.3.1331-1339.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zweerink M. M., Edison A. Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids. Antimicrob Agents Chemother. 1986 Apr;29(4):598–601. doi: 10.1128/aac.29.4.598. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES