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gyrA  -  DNA gyrase subunit A

Streptococcus pneumoniae R6

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Disease relevance of gyrA


High impact information on gyrA

  • Fluoroquinolone resistance in Streptococcus pneumoniae is primarily mediated by point mutations in the quinolone resistance-determining regions of gyrA and parC [6].
  • Naturally occurring parC, parE, and gyrA loci containing mutations in the quinolone-resistance-determining regions were introduced by transformation into S. pneumoniae strain R6 individually and in combinations [7].
  • PD models simulating fAUC/MICs of 51 and </=60, 34 and 37, </=82 and </=86, and </=24 for gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, respectively, against each isolate were associated with first-step parC (S52G, S79Y, and N91D) and second-step gyrA (S81Y and S114G) mutations [8].
  • First, ciprofloxacin-resistant parC mutants of strain 7785 remained susceptible to dimers 1 to 3, whereas a gyrA mutation conferred a four- to eightfold increase in the dimer MIC but had little effect on ciprofloxacin activity [9].
  • Therapeutic moxifloxacin concentrations against the gyrA mutant KD2139 resulted in outgrowth of a mutant with a ParC substitution (S79Y) but caused no emergence of mutants of the other three isolates [10].

Chemical compound and disease context of gyrA


Biological context of gyrA


Associations of gyrA with chemical compounds

  • With S. aureus, the dimer selected spontaneous resistant gyrA mutants, whereas ciprofloxacin selected a parC mutant [1].
  • The isolate obtained before therapy showed a preexisting parC mutation of aspartic acid-83 to asparagine (Asp83-->Asn), and the isolate obtained during therapy showed an acquired gyrA mutation from serine-81 to phenylalanine (Ser81-->Phe) and a second parC mutation from lysine-137 to Asn (Lys137-->Asn) [2].
  • (ii) Gemifloxacin selected first-step gyrA mutants of S. pneumoniae 7785 (gemifloxacin MICs, 0.25 microgram/ml) encoding Ser-81 to Phe or Tyr, or Glu-85 to Lys mutations [16].
  • The gyrA mutants were cross-resistant to gatifloxacin and sparfloxacin but were not resistant to the other fluoroquinolones tested [17].
  • Exposure to DK-507k and sitafloxacin resulted in mutations, mostly in gyrA [18].

Other interactions of gyrA


Analytical, diagnostic and therapeutic context of gyrA


  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. Selection of a gyrA Mutation and Treatment Failure with Gatifloxacin in a Patient with Streptococcus pneumoniae with a Preexisting parC Mutation. Kays, M.B., Zhanel, G.G., Reimann, M.A., Jacobi, J., Denys, G.A., Smith, D.W., Wack, M.F. Pharmacotherapy (2007) [Pubmed]
  3. Resistance to multiple fluoroquinolones in a clinical isolate of Streptococcus pyogenes: identification of gyrA and parC and specification of point mutations associated with resistance. Yan, S.S., Fox, M.L., Holland, S.M., Stock, F., Gill, V.J., Fedorko, D.P. Antimicrob. Agents Chemother. (2000) [Pubmed]
  4. In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point. Alkorta, M., Giménez, M.J., Vicente, D., Aguilar, L., Pérez-Trallero, E. Int. J. Antimicrob. Agents (2005) [Pubmed]
  5. Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections. Klugman, K.P. The European respiratory journal. Supplement. (2002) [Pubmed]
  6. Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae. Johnson, C.N., Briles, D.E., Benjamin, W.H., Hollingshead, S.K., Waites, K.B. Emerging Infect. Dis. (2005) [Pubmed]
  7. Fitness Costs of Fluoroquinolone Resistance in Streptococcus pneumoniae. Rozen, D.E., McGee, L., Levin, B.R., Klugman, K.P. Antimicrob. Agents Chemother. (2007) [Pubmed]
  8. Fluoroquinolone Resistance in Streptococcus pneumoniae: Area Under the Concentration-Time Curve/MIC Ratio and Resistance Development with Gatifloxacin, Gemifloxacin, Levofloxacin, and Moxifloxacin. Laplante, K.L., Rybak, M.J., Tsuji, B., Lodise, T.P., Kaatz, G.W. Antimicrob. Agents Chemother. (2007) [Pubmed]
  9. Ciprofloxacin dimers target gyrase in Streptococcus pneumoniae. Gould, K.A., Pan, X.S., Kerns, R.J., Fisher, L.M. Antimicrob. Agents Chemother. (2004) [Pubmed]
  10. Activities of mutant prevention concentration-targeted moxifloxacin and levofloxacin against Streptococcus pneumoniae in an in vitro pharmacodynamic model. Allen, G.P., Kaatz, G.W., Rybak, M.J. Antimicrob. Agents Chemother. (2003) [Pubmed]
  11. Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci. González, I., Georgiou, M., Alcaide, F., Balas, D., Liñares, J., de la Campa, A.G. Antimicrob. Agents Chemother. (1998) [Pubmed]
  12. Sparfloxacin resistance in clinical isolates of Streptococcus pneumoniae: involvement of multiple mutations in gyrA and parC genes. Taba, H., Kusano, N. Antimicrob. Agents Chemother. (1998) [Pubmed]
  13. Relationship between mutations in parC and gyrA of clinical isolates of Streptococcus pneumoniae and resistance to ciprofloxacin and grepafloxacin. Stewart, B.A., Johnson, A.P., Woodford, N. J. Med. Microbiol. (1999) [Pubmed]
  14. Molecular characterization of the gene encoding the DNA gyrase A subunit of Streptococcus pneumoniae. Balas, D., Fernández-Moreira, E., De La Campa, A.G. J. Bacteriol. (1998) [Pubmed]
  15. Fluoroquinolone resistance in Streptococcus pneumoniae: evidence that gyrA mutations arise at a lower rate and that mutation in gyrA or parC predisposes to further mutation. Gillespie, S.H., Voelker, L.L., Ambler, J.E., Traini, C., Dickens, A. Microb. Drug Resist. (2003) [Pubmed]
  16. Potent antipneumococcal activity of gemifloxacin is associated with dual targeting of gyrase and topoisomerase IV, an in vivo target preference for gyrase, and enhanced stabilization of cleavable complexes in vitro. Heaton, V.J., Ambler, J.E., Fisher, L.M. Antimicrob. Agents Chemother. (2000) [Pubmed]
  17. Primary targets of fluoroquinolones in Streptococcus pneumoniae. Fukuda, H., Hiramatsu, K. Antimicrob. Agents Chemother. (1999) [Pubmed]
  18. Antipneumococcal activity of DK-507k, a new quinolone, compared with the activities of 10 other agents. Browne, F.A., Bozdogan, B., Clark, C., Kelly, L.M., Ednie, L., Kosowska, K., Dewasse, B., Jacobs, M.R., Appelbaum, P.C. Antimicrob. Agents Chemother. (2003) [Pubmed]
  19. Genetic analyses of mutations contributing to fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. Weigel, L.M., Anderson, G.J., Facklam, R.R., Tenover, F.C. Antimicrob. Agents Chemother. (2001) [Pubmed]
  20. Prevalence of gyrA, gyrB, parC, and parE mutations in clinical isolates of Streptococcus pneumoniae with decreased susceptibilities to different fluoroquinolones and originating from Worldwide Surveillance Studies during the 1997-1998 respiratory season. Jones, M.E., Sahm, D.F., Martin, N., Scheuring, S., Heisig, P., Thornsberry, C., Köhrer, K., Schmitz, F.J. Antimicrob. Agents Chemother. (2000) [Pubmed]
  21. Evolutionary barriers to quinolone resistance in Streptococcus pneumoniae. Gillespie, S.H., Voelker, L.L., Dickens, A. Microb. Drug Resist. (2002) [Pubmed]
  22. Emergence and epidemiology of fluoroquinolone-resistant Streptococcus pneumoniae strains from Italy: report from the SENTRY Antimicrobial Surveillance Program (2001-2004). Deshpande, L.M., Sader, H.S., Debbia, E., Nicoletti, G., Fadda, G., Jones, R.N. Diagn. Microbiol. Infect. Dis. (2006) [Pubmed]
  23. The molecular epidemiology of Streptococcus pneumoniae with quinolone resistance mutations. Richter, S.S., Heilmann, K.P., Beekmann, S.E., Miller, N.J., Rice, C.L., Doern, G.V. Clin. Infect. Dis. (2005) [Pubmed]
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