Abstract
As a means of gaining information on the selectivity of quinolone antibacterial agents, we examined their effect on four topoisomerases, topoisomerases I and II purified from Escherichia coli and calf thymus. The inhibition of supercoiling and relaxation activities was monitored by using the classical gel electrophoresis assay. Eight quinolones were assayed by using the four enzymes. Gyrase was much more sensitive to quinolones than the other topoisomerases which can therefore be inhibited by moderate concentrations of certain quinolones. No good correlation was observed between the activity on gyrase and on the other enzymes, since the ratio varied from 15 to more than 8,500. On the contrary, there was a good correlation between early inhibition of DNA synthesis, inhibition of gyrase, and MICs.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barrett J. F., Gootz T. D., McGuirk P. R., Farrell C. A., Sokolowski S. A. Use of in vitro topoisomerase II assays for studying quinolone antibacterial agents. Antimicrob Agents Chemother. 1989 Oct;33(10):1697–1703. doi: 10.1128/aac.33.10.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrett J. F., Sutcliffe J. A., Gootz T. D. In vitro assays used to measure the activity of topoisomerases. Antimicrob Agents Chemother. 1990 Jan;34(1):1–7. doi: 10.1128/aac.34.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bouzard D., Di Cesare P., Essiz M., Jacquet J. P., Kiechel J. R., Remuzon P., Weber A., Oki T., Masuyoshi M., Kessler R. E. Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives. J Med Chem. 1990 May;33(5):1344–1352. doi: 10.1021/jm00167a010. [DOI] [PubMed] [Google Scholar]
- Bouzard D., Di Cesare P., Essiz M., Jacquet J. P., Remuzon P., Weber A., Oki T., Masuyoshi M. Fluoronaphthyridines and quinolones as antibacterial agents. 1. Synthesis and structure-activity relationships of new 1-substituted derivatives. J Med Chem. 1989 Mar;32(3):537–542. doi: 10.1021/jm00123a005. [DOI] [PubMed] [Google Scholar]
- Chow R. T., Dougherty T. J., Fraimow H. S., Bellin E. Y., Miller M. H. Association between early inhibition of DNA synthesis and the MICs and MBCs of carboxyquinolone antimicrobial agents for wild-type and mutant [gyrA nfxB(ompF) acrA] Escherichia coli K-12. Antimicrob Agents Chemother. 1988 Aug;32(8):1113–1118. doi: 10.1128/aac.32.8.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chu D. T., Fernandes P. B. Structure-activity relationships of the fluoroquinolones. Antimicrob Agents Chemother. 1989 Feb;33(2):131–135. doi: 10.1128/aac.33.2.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Drlica K., Engle E. C., Manes S. H. DNA gyrase on the bacterial chromosome: possibility of two levels of action. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6879–6883. doi: 10.1073/pnas.77.11.6879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drlica K., Franco R. J. Inhibitors of DNA topoisomerases. Biochemistry. 1988 Apr 5;27(7):2253–2259. doi: 10.1021/bi00407a001. [DOI] [PubMed] [Google Scholar]
- Fernandes P. B. Mode of action, and in vitro and in vivo activities of the fluoroquinolones. J Clin Pharmacol. 1988 Feb;28(2):156–168. doi: 10.1002/j.1552-4604.1988.tb05967.x. [DOI] [PubMed] [Google Scholar]
- Forsgren A., Bredberg A., Pardee A. B., Schlossman S. F., Tedder T. F. Effects of ciprofloxacin on eucaryotic pyrimidine nucleotide biosynthesis and cell growth. Antimicrob Agents Chemother. 1987 May;31(5):774–779. doi: 10.1128/aac.31.5.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forsgren A., Schlossman S. F., Tedder T. F. 4-Quinolone drugs affect cell cycle progression and function of human lymphocytes in vitro. Antimicrob Agents Chemother. 1987 May;31(5):768–773. doi: 10.1128/aac.31.5.768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gonzalez J. P., Henwood J. M. Pefloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1989 May;37(5):628–668. doi: 10.2165/00003495-198937050-00003. [DOI] [PubMed] [Google Scholar]
- Gootz T. D., Barrett J. F., Sutcliffe J. A. Inhibitory effects of quinolone antibacterial agents on eucaryotic topoisomerases and related test systems. Antimicrob Agents Chemother. 1990 Jan;34(1):8–12. doi: 10.1128/aac.34.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halligan B. D., Edwards K. A., Liu L. F. Purification and characterization of a type II DNA topoisomerase from bovine calf thymus. J Biol Chem. 1985 Feb 25;260(4):2475–2482. [PubMed] [Google Scholar]
- Holden H. E., Barett J. F., Huntington C. M., Muehlbauer P. A., Wahrenburg M. G. Genetic profile of a nalidixic acid analog: a model for the mechanism of sister chromatid exchange induction. Environ Mol Mutagen. 1989;13(3):238–252. doi: 10.1002/em.2850130308. [DOI] [PubMed] [Google Scholar]
- Hoshino K., Sato K., Une T., Osada Y. Inhibitory effects of quinolones on DNA gyrase of Escherichia coli and topoisomerase II of fetal calf thymus. Antimicrob Agents Chemother. 1989 Oct;33(10):1816–1818. doi: 10.1128/aac.33.10.1816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsiang Y. H., Hertzberg R., Hecht S., Liu L. F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem. 1985 Nov 25;260(27):14873–14878. [PubMed] [Google Scholar]
- Hussy P., Maass G., Tümmler B., Grosse F., Schomburg U. Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts. Antimicrob Agents Chemother. 1986 Jun;29(6):1073–1078. doi: 10.1128/aac.29.6.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lynn R., Giaever G., Swanberg S. L., Wang J. C. Tandem regions of yeast DNA topoisomerase II share homology with different subunits of bacterial gyrase. Science. 1986 Aug 8;233(4764):647–649. doi: 10.1126/science.3014661. [DOI] [PubMed] [Google Scholar]
- Maxwell A., Gellert M. Mechanistic aspects of DNA topoisomerases. Adv Protein Chem. 1986;38:69–107. doi: 10.1016/s0065-3233(08)60526-4. [DOI] [PubMed] [Google Scholar]
- Minford J., Pommier Y., Filipski J., Kohn K. W., Kerrigan D., Mattern M., Michaels S., Schwartz R., Zwelling L. A. Isolation of intercalator-dependent protein-linked DNA strand cleavage activity from cell nuclei and identification as topoisomerase II. Biochemistry. 1986 Jan 14;25(1):9–16. doi: 10.1021/bi00349a002. [DOI] [PubMed] [Google Scholar]
- Oomori Y., Yasue T., Aoyama H., Hirai K., Suzue S., Yokota T. Effects of fleroxacin on HeLa cell functions and topoisomerase II. J Antimicrob Chemother. 1988 Oct;22 (Suppl 500):91–97. doi: 10.1093/jac/22.supplement_d.91. [DOI] [PubMed] [Google Scholar]
- Otter R., Cozzarelli N. R. Escherichia coli DNA gyrase. Methods Enzymol. 1983;100:171–180. doi: 10.1016/0076-6879(83)00053-1. [DOI] [PubMed] [Google Scholar]
- Rusquet R., Bonhommet M., David J. C. Quinolone antibiotics inhibit eucaryotic DNA polymerase alpha and beta, terminal deoxynucleotidyl transferase but not DNA ligase. Biochem Biophys Res Commun. 1984 Jun 29;121(3):762–769. doi: 10.1016/0006-291x(84)90744-7. [DOI] [PubMed] [Google Scholar]
- Schomburg U., Grosse F. Purification and characterization of DNA topoisomerase II from calf thymus associated with polypeptides of 175 and 150 kDa. Eur J Biochem. 1986 Nov 3;160(3):451–457. doi: 10.1111/j.1432-1033.1986.tb10061.x. [DOI] [PubMed] [Google Scholar]
- Sioud M., Forterre P. Ciprofloxacin and etoposide (VP16) produce a similar pattern of DNA cleavage in a plasmid of an archaebacterium. Biochemistry. 1989 May 2;28(9):3638–3641. doi: 10.1021/bi00435a002. [DOI] [PubMed] [Google Scholar]
- 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]
- Tabary X., Moreau N., Dureuil C., Le Goffic F. Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and clorobiocin on Escherichia coli topoisomerase I. Antimicrob Agents Chemother. 1987 Dec;31(12):1925–1928. doi: 10.1128/aac.31.12.1925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tornaletti S., Pedrini A. M. Studies on the interaction of 4-quinolones with DNA by DNA unwinding experiments. Biochim Biophys Acta. 1988 Mar 31;949(3):279–287. doi: 10.1016/0167-4781(88)90153-4. [DOI] [PubMed] [Google Scholar]
- Vosberg H. P. DNA topoisomerases: enzymes that control DNA conformation. Curr Top Microbiol Immunol. 1985;114:19–102. doi: 10.1007/978-3-642-70227-3_2. [DOI] [PubMed] [Google Scholar]
- Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
- Wang J. C., Kirkegaard K. DNA topoisomerases. Gene Amplif Anal. 1981;2:455–473. [PubMed] [Google Scholar]