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Gene Review

gyrA  -  DNA gyrase subunit A

Staphylococcus aureus RF122

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Disease relevance of gyrA


High impact information on gyrA

  • All first- and second-step mutants selected by WCK 771 revealed gyrA and grlA mutations, respectively [3].
  • Our results demonstrate that gyrA is the primary target of WCK 771 and that it has pharmacodynamic properties remarkably different from those of quinolones with dual targets (garenoxacin and moxifloxacin) and topoisomerase IV-specific quinolones (trovafloxacin) [3].
  • Species identification was confirmed by standard biochemical tests and analysis of 16S ribosomal DNA, gyrA, and gyrB sequences; all of the results were consistent with the S. aureus identification [4].
  • There was no relationship between the time that ciprofloxacin concentrations remained between the MIC and the MPC and the degree of resistance or the presence or type of ciprofloxacin-resistance mutations that appeared in grlA or gyrA [5].
  • The two- to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 x 10(-11) to 1.1 x 10(-10)), suggested similar targeting of the two enzymes by gemifloxacin [6].

Chemical compound and disease context of gyrA


Biological context of gyrA

  • The elimination of this plasmid from such quinolone-resistant gyrA mutants resulted in marked increases in quinolone susceptibility [11].
  • A total of 36 clinical isolates of Staphylococcus aureus (29 fluoroquinolone-resistant strains and 7 fluoroquinolone-susceptible strains) were studied for the presence of point mutations in the gyrA gene by nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis with silver stain [12].
  • Restriction fragment length polymorphism (RFLP) patterns around the gyrA gene in CNS were identical, but species specific, for all 10 MRSE and 10 MRSH isolates examined [13].
  • A mutation of the gyrA gene resulting in an amino acid substitution was found in the second-step but not in the first-step resistant subclone [14].
  • At saturating drug concentrations, norfloxacin and a gyrA mutant were used to show that topoisomerase IV-norfloxacin-cleaved DNA complexes are distributed on the S. aureus chromosome at intervals of about 30 kbp [15].

Associations of gyrA with chemical compounds


Regulatory relationships of gyrA

  • The silent mutant allele of gyrA was present in a flqA background and expressed resistance only upon introduction of a grlA mutation [20].

Other interactions of gyrA

  • Portions of the gyrA (codons 60 to 120) and the gyrB (codons 420 to 480) genes of each clinical isolate were amplified by PCR and sequenced [21].
  • A double mutation (gyrA and either grlA or grlB) caused a 32-fold increase in the MIC of premafloxacin, while the MIC of ciprofloxacin increased 128-fold [22].
  • Two genes previously associated with fluoroquinolone resistance, the gyrA gene of DNA gyrase and the norA gene (associated with decreased drug accumulation), were localized to the G and D fragments, respectively [23].
  • For all target genes, the expression profiles obtained with gyrA or gmk as internal standards remained almost identical [24].

Analytical, diagnostic and therapeutic context of gyrA

  • gyrA mutations in quinolone-resistant pathogenic isolates of Staphylococcus spp. have been detected by the direct HinfI digestion of polymerase chain reaction products [25].


  1. Bactericidal activity and target preference of a piperazinyl-cross-linked ciprofloxacin dimer with Staphylococcus aureus and Escherichia coli. Zhao, X., Quinn, B., Kerns, R., Drlica, K. J. Antimicrob. Chemother. (2006) [Pubmed]
  2. Incidence of various gyrA mutants in 451 Staphylococcus aureus strains isolated in Japan and their susceptibilities to 10 fluoroquinolones. Takenouchi, T., Ishii, C., Sugawara, M., Tokue, Y., Ohya, S. Antimicrob. Agents Chemother. (1995) [Pubmed]
  3. The Anti-Methicillin-Resistant Staphylococcus aureus Quinolone WCK 771 Has Potent Activity against Sequentially Selected Mutants, Has a Narrow Mutant Selection Window against Quinolone-Resistant Staphylococcus aureus, and Preferentially Targets DNA Gyrase. Bhagwat, S.S., Mundkur, L.A., Gupte, S.V., Patel, M.V., Khorakiwala, H.F. Antimicrob. Agents Chemother. (2006) [Pubmed]
  4. Vancomycin-resistant Staphylococcus aureus isolate from a patient in Pennsylvania. Tenover, F.C., Weigel, L.M., Appelbaum, P.C., McDougal, L.K., Chaitram, J., McAllister, S., Clark, N., Killgore, G., O'Hara, C.M., Jevitt, L., Patel, J.B., Bozdogan, B. Antimicrob. Agents Chemother. (2004) [Pubmed]
  5. Evolution of ciprofloxacin-resistant Staphylococcus aureus in in vitro pharmacokinetic environments. Campion, J.J., McNamara, P.J., Evans, M.E. Antimicrob. Agents Chemother. (2004) [Pubmed]
  6. Topoisomerase targeting with and resistance to gemifloxacin in Staphylococcus aureus. Ince, D., Zhang, X., Silver, L.C., Hooper, D.C. Antimicrob. Agents Chemother. (2003) [Pubmed]
  7. Detection of gyrA gene mutations associated with ciprofloxacin resistance in methicillin-resistant Staphylococcus aureus: analysis by polymerase chain reaction and automated direct DNA sequencing. Goswitz, J.J., Willard, K.E., Fasching, C.E., Peterson, L.R. Antimicrob. Agents Chemother. (1992) [Pubmed]
  8. Efficacies of moxifloxacin, ciprofloxacin, and vancomycin against experimental endocarditis due to methicillin-resistant Staphylococcus aureus expressing various degrees of ciprofloxacin resistance. Entenza, J.M., Que, Y.A., Vouillamoz, J., Glauser, M.P., Moreillon, P. Antimicrob. Agents Chemother. (2001) [Pubmed]
  9. Quinolone resistance in Staphylococci: activities of new nonfluorinated quinolones against molecular targets in whole cells and clinical isolates. Roychoudhury, S., Catrenich, C.E., McIntosh, E.J., McKeever, H.D., Makin, K.M., Koenigs, P.M., Ledoussal, B. Antimicrob. Agents Chemother. (2001) [Pubmed]
  10. Bactericidal activities of BMS-284756, a novel Des-F(6)-quinolone, against Staphylococcus aureus strains with topoisomerase mutations. Lawrence, L.E., Frosco, M., Ryan, B., Chaniewski, S., Yang, H., Hooper, D.C., Barrett, J.F. Antimicrob. Agents Chemother. (2002) [Pubmed]
  11. Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus. Yamagishi, J., Kojima, T., Oyamada, Y., Fujimoto, K., Hattori, H., Nakamura, S., Inoue, M. Antimicrob. Agents Chemother. (1996) [Pubmed]
  12. Detection of novel mutations in the gyrA gene of Staphylococcus aureus by nonradioisotopic single-strand conformation polymorphism analysis and direct DNA sequencing. Tokue, Y., Sugano, K., Saito, D., Noda, T., Ohkura, H., Shimosato, Y., Sekiya, T. Antimicrob. Agents Chemother. (1994) [Pubmed]
  13. Determination of the chromosomal relationship between mecA and gyrA in methicillin-resistant coagulase-negative staphylococci. Fey, P.D., Climo, M.W., Archer, G.L. Antimicrob. Agents Chemother. (1998) [Pubmed]
  14. Sequential acquisition of norfloxacin and ofloxacin resistance by methicillin-resistant and -susceptible Staphylococcus aureus. Hori, S., Ohshita, Y., Utsui, Y., Hiramatsu, K. Antimicrob. Agents Chemother. (1993) [Pubmed]
  15. Selective targeting of topoisomerase IV and DNA gyrase in Staphylococcus aureus: different patterns of quinolone-induced inhibition of DNA synthesis. Fournier, B., Zhao, X., Lu, T., Drlica, K., Hooper, D.C. Antimicrob. Agents Chemother. (2000) [Pubmed]
  16. Topoisomerase mutations in fluoroquinolone-resistant and methicillin-susceptible and -resistant clinical isolates of Staphylococcus aureus. Kaatz, G.W., Seo, S.M. Antimicrob. Agents Chemother. (1998) [Pubmed]
  17. Improved bactericidal activity of Q-35 against quinolone-resistant staphylococci. Ito, T., Matsumoto, M., Nishino, T. Antimicrob. Agents Chemother. (1995) [Pubmed]
  18. Mechanisms and frequency of resistance to gatifloxacin in comparison to AM-1121 and ciprofloxacin in Staphylococcus aureus. Ince, D., Hooper, D.C. Antimicrob. Agents Chemother. (2001) [Pubmed]
  19. Mutations in topoisomerase IV and DNA gyrase of Staphylococcus aureus: novel pleiotropic effects on quinolone and coumarin activity. Fournier, B., Hooper, D.C. Antimicrob. Agents Chemother. (1998) [Pubmed]
  20. Quinolone resistance mutations in topoisomerase IV: relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus. Ng, E.Y., Trucksis, M., Hooper, D.C. Antimicrob. Agents Chemother. (1996) [Pubmed]
  21. In vivo selection during pefloxacin therapy of a mutant of Staphylococcus aureus with two mechanisms of fluoroquinolone resistance. Tankovic, J., Desplaces, N., Duval, J., Courvalin, P. Antimicrob. Agents Chemother. (1994) [Pubmed]
  22. Mechanisms and frequency of resistance to premafloxacin in Staphylococcus aureus: novel mutations suggest novel drug-target interactions. Ince, D., Hooper, D.C. Antimicrob. Agents Chemother. (2000) [Pubmed]
  23. A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus. Trucksis, M., Wolfson, J.S., Hooper, D.C. J. Bacteriol. (1991) [Pubmed]
  24. Comparison of two standardisation methods in real-time quantitative RT-PCR to follow Staphylococcus aureus genes expression during in vitro growth. Eleaume, H., Jabbouri, S. J. Microbiol. Methods (2004) [Pubmed]
  25. Ciprofloxacin resistance in coagulase-positive and -negative staphylococci: role of mutations at serine 84 in the DNA gyrase A protein of Staphylococcus aureus and Staphylococcus epidermidis. Sreedharan, S., Peterson, L.R., Fisher, L.M. Antimicrob. Agents Chemother. (1991) [Pubmed]
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