Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Nov;35(11):2288–2293. doi: 10.1128/aac.35.11.2288

Inhibitory effects of ciprofloxacin and sparfloxacin on DNA gyrase purified from fluoroquinolone-resistant strains of methicillin-resistant Staphylococcus aureus.

J Okuda 1, S Okamoto 1, M Takahata 1, T Nishino 1
PMCID: PMC245373  PMID: 1666495

Abstract

The activities of new quinolones against 140 strains of methicillin-resistant Staphylococcus aureus were determined. From the relationship between the MICs of sparfloxacin and ciprofloxacin, fluoroquinolone-resistant S. aureus 6171 (MIC of sparfloxacin, 200 micrograms/ml; MIC of ciprofloxacin, 100 micrograms/ml) and fluoroquinolone-susceptible S. aureus FDA 209-P were selected for purification of the subunit A and B proteins of their DNA gyrases. The supercoiling activities of reconstituted ArBr (r, resistant) (from strain 6171) and ArBs (s, susceptible) gyrases were 40-fold more resistant to new quinolones than those of AsBs from FDA 209-P and AsBr gyrases. The 50% inhibitory doses of ciprofloxacin and sparfloxacin for AmBm (from mutant 19) and AmBs (m, moderately resistant) gyrases were 15- to 27-fold higher than those for AsBs and AsBm gyrases. These findings indicate that one of the resistance mechanisms of S. aureus against fluoroquinolones is a modification of the gyrase subunit A protein.

Full text

PDF

Images in this article

2291Image
on p.2291

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. Daikos G. L., Lolans V. T., Jackson G. G. Alterations in outer membrane proteins of Pseudomonas aeruginosa associated with selective resistance to quinolones. Antimicrob Agents Chemother. 1988 May;32(5):785–787. doi: 10.1128/aac.32.5.785. [DOI] [PMC free article] [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. Espinoza A. M., Chin N. X., Novelli A., Neu H. C. Comparative in vitro activity of a new fluorinated 4-quinolone, T-3262 (A-60969). Antimicrob Agents Chemother. 1988 May;32(5):663–670. doi: 10.1128/aac.32.5.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fass R. J. In vitro activity of ciprofloxacin (Bay o 9867). Antimicrob Agents Chemother. 1983 Oct;24(4):568–574. doi: 10.1128/aac.24.4.568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Hirai K., Aoyama H., Hosaka M., Oomori Y., Niwata Y., Suzue S., Irikura T. In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative. Antimicrob Agents Chemother. 1986 Jun;29(6):1059–1066. doi: 10.1128/aac.29.6.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hirai K., Aoyama H., Suzue S., Irikura T., Iyobe S., Mitsuhashi S. Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K-12. Antimicrob Agents Chemother. 1986 Aug;30(2):248–253. doi: 10.1128/aac.30.2.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hirai K., Suzue S., Irikura T., Iyobe S., Mitsuhashi S. Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1987 Apr;31(4):582–586. doi: 10.1128/aac.31.4.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kojima T., Inoue M., Mitsuhashi S. In vitro activity of AT-4140 against quinolone- and methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1990 Jun;34(6):1123–1127. doi: 10.1128/aac.34.6.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Konno M., Ohonari S., Itoh N., Ubukata K., Hashimoto Y., Kawakami S. [Trends of fluoroquinolone-resistant strains isolated from clinical materials]. Kansenshogaku Zasshi. 1988 Jul;62(7):641–651. doi: 10.11150/kansenshogakuzasshi1970.62.641. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. Sreedharan S., Oram M., Jensen B., Peterson L. R., Fisher L. M. DNA gyrase gyrA mutations in ciprofloxacin-resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli. J Bacteriol. 1990 Dec;172(12):7260–7262. doi: 10.1128/jb.172.12.7260-7262.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Takahata M., Nishino T. DNA gyrase of Staphylococcus aureus and inhibitory effect of quinolones on its activity. Antimicrob Agents Chemother. 1988 Aug;32(8):1192–1195. doi: 10.1128/aac.32.8.1192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Takahata M., Otsuki M., Nishino T. In-vitro and in-vivo activities of T-3262, a new pyridone carboxylic acid. J Antimicrob Chemother. 1988 Aug;22(2):143–154. doi: 10.1093/jac/22.2.143. [DOI] [PubMed] [Google Scholar]
  19. Tanaka M., Sato K., Kimura Y., Hayakawa I., Osada Y., Nishino T. Inhibition by quinolones of DNA gyrase from Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Jul;35(7):1489–1491. doi: 10.1128/aac.35.7.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yoshida H., Bogaki M., Nakamura S., Ubukata K., Konno M. Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol. 1990 Dec;172(12):6942–6949. doi: 10.1128/jb.172.12.6942-6949.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Yoshida S., Kojima T., Inoue M., Mitsuhashi S. Uptake of sparfloxacin and norfloxacin by clinical isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 1991 Feb;35(2):368–370. doi: 10.1128/aac.35.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES