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Gene Review

gyrA  -  DNA gyrase (type II topoisomerase), subunit A

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK2223, JW2225, hisW, nalA, nfxA, ...
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Disease relevance of gyrA


High impact information on gyrA

  • In the Deltafis strain, both topA and gyrA/B genes were found to be upregulated [5].
  • The hisU1820 mutant of S. typhimurium exhibits many of the same phenotypes as hisW mutants [6].
  • The hisW mutations of Salmonella typhimurium are highly pleiotropic mutations that elevate his operon expression, reduce ilv gene expression, alter stable RNA metabolism, and confer defective growth properties [6].
  • The subunits can be identified as the products of two genes, determining resistance to coumermycin A1 and novobiocin (cou) and to nalidixic acid and oxolinic acid (nalA), respectively [7].
  • Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme [8].

Chemical compound and disease context of gyrA

  • Fusions of the Escherichia coli gyrA and gyrB control regions to the galactokinase gene are inducible by coumermycin treatment [9].
  • Enoxacin inhibits growth of Escherichia coli K12 strains primarily by binding to the GyrA subunit of DNA gyrase (topoisomerase II); strains with gyrA, but not gyrB, mutations are less susceptible to the bactericidal effects of this agent [10].
  • In the absence of the gyrA mutation, the parC (CipR) allele did not by itself confer resistance to ciprofloxacin, indicating that gyrase is the major quinolone target in E. coli [11].
  • Treatment with EDTA decreased the ID50 of ciprofloxacin for P. aeruginosa PAO503 and its gyrA derivative by 5- and 2-fold, respectively, and decreased the ID50 for E. coli JB5R, a strain with a known decrease in OmpF, by 1.4-fold but did not decrease the ID50 for the normally susceptible E. coli J53 [12].
  • gyrA and parC mutations have been identified inn Streptococcus pneumoniae mutants stepwise selected for resistance to sparfloxacin, an antipneumococcal fluoroquinolone [13].

Biological context of gyrA

  • Fragments of gyrA and parC encompassing the quinolone resistance-determining region were amplified by PCR, and the DNA sequences of the fragments were determined [14].
  • Introduction of a plasmid carrying both gyrA and gyrB genes into S. typhimurium 80190 restored the wildtype sensitivity [15].
  • Enoxacin, even at subminimal inhibitory concentrations, induces the bacterial SOS system, even in partially resistant gyrA strains [10].
  • The nucleotide sequence of gyrA was highly homologous to those of other bacterial species, in both the whole open-reading frame and the quinolone-resistance-determining region (QRDR) [3].
  • The 2637-bp gyrA gene encodes a protein of 878 amino acids, preceded by a putative promoter, ribosome binding site and inverted repeated sequences for cruciform structures of DNA [3].

Anatomical context of gyrA


Associations of gyrA with chemical compounds

  • There were significant differences (P less than 0.001) between individual quinolones in the degree of DNA synthesis inhibition in nalidixic acid-resistant gyrA and nfxB(ompF) mutant strains [1].
  • All isolates contained a mutation in gyrA of a serine at position 83 (Ser83) to an Leu, and 26 isolates also contained a mutation of Asp87 to one of four amino acids: Asn (n = 14), Tyr (n = 6), Gly (n = 5), or His (n = 1) [14].
  • One, designated cfxA, conferred a 16-fold increase in drug resistance and mapped in a location consistent with a gyrA mutation; similar increases in resistance to ciprofloxacin were seen with gyrA mutations selected for resistance to other quinolones [17].
  • The nucleotide sequence revealed that one of the gyrA mutants has a base change from G to A at position 641 (resulting in an amino acid change from Gly to Glu at position 214) of the gyrA gene [18].
  • These results demonstrate that in clinical practice, gyrA mutations are the major mechanism of resistance to fluoroquinolones even in the strains of P. aeruginosa resistant to imipenem and lacking OprD, concomitant resistance to these drugs being the result of the addition of at least two independent mechanisms [19].

Regulatory relationships of gyrA

  • We examined, in Escherichia coli, the influence of recA mutant alleles on the level of quinolone resistance promoted by mutations in the gyrA gene [20].

Other interactions of gyrA


Analytical, diagnostic and therapeutic context of gyrA


  1. 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. Chow, R.T., Dougherty, T.J., Fraimow, H.S., Bellin, E.Y., Miller, M.H. Antimicrob. Agents Chemother. (1988) [Pubmed]
  2. Identification of the plasmid-borne quinolone resistance gene qnrS in Salmonella enterica serovar Infantis. Kehrenberg, C., Friederichs, S., de Jong, A., Michael, G.B., Schwarz, S. J. Antimicrob. Chemother. (2006) [Pubmed]
  3. Molecular cloning of the gyrA gene and characterization of its mutation in clinical isolates of quinolone-resistant Edwardsiella tarda. Shin, S.B., Yoo, M.H., Jeong, J.B., Kim, Y.M., Chung, J.K., Huh, M.D., Komisar, J.L., Jeong, H.D. Dis. Aquat. Org. (2005) [Pubmed]
  4. Cloning and sequencing of the Escherichia coli gyrA gene coding for the A subunit of DNA gyrase. Swanberg, S.L., Wang, J.C. J. Mol. Biol. (1987) [Pubmed]
  5. Dynamic state of DNA topology is essential for genome condensation in bacteria. Ohniwa, R.L., Morikawa, K., Kim, J., Ohta, T., Ishihama, A., Wada, C., Takeyasu, K. EMBO J. (2006) [Pubmed]
  6. his operons of Escherichia coli and Salmonella typhimurium are regulated by DNA supercoiling. Rudd, K.E., Menzel, R. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  7. DNA gyrase: subunit structure and ATPase activity of the purified enzyme. Mizuuchi, K., O'Dea, M.H., Gellert, M. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  8. Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Sugino, A., Peebles, C.L., Kreuzer, K.N., Cozzarelli, N.R. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  9. Fusions of the Escherichia coli gyrA and gyrB control regions to the galactokinase gene are inducible by coumermycin treatment. Menzel, R., Gellert, M. J. Bacteriol. (1987) [Pubmed]
  10. Alteration of bacterial DNA structure, gene expression, and plasmid encoded antibiotic resistance following exposure to enoxacin. Courtright, J.B., Turowski, D.A., Sonstein, S.A. J. Antimicrob. Chemother. (1988) [Pubmed]
  11. DNA gyrase and topoisomerase IV on the bacterial chromosome: quinolone-induced DNA cleavage. Chen, C.R., Malik, M., Snyder, M., Drlica, K. J. Mol. Biol. (1996) [Pubmed]
  12. Contribution of permeability and sensitivity to inhibition of DNA synthesis in determining susceptibilities of Escherichia coli, Pseudomonas aeruginosa, and Alcaligenes faecalis to ciprofloxacin. Bedard, J., Chamberland, S., Wong, S., Schollaardt, T., Bryan, L.E. Antimicrob. Agents Chemother. (1989) [Pubmed]
  13. Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones. Pan, X.S., Fisher, L.M. Antimicrob. Agents Chemother. (1997) [Pubmed]
  14. Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Everett, M.J., Jin, Y.F., Ricci, V., Piddock, L.J. Antimicrob. Agents Chemother. (1996) [Pubmed]
  15. High-level fluoroquinolone resistance in a Salmonella typhimurium isolate due to alterations in both gyrA and gyrB genes. Heisig, P. J. Antimicrob. Chemother. (1993) [Pubmed]
  16. Sequential mutations of gyrA in Escherichia coli associated with quinolone therapy. Truong, Q.C., Ouabdesselam, S., Hooper, D.C., Moreau, N.J., Soussy, C.J. J. Antimicrob. Chemother. (1995) [Pubmed]
  17. Mechanisms of action of and resistance to ciprofloxacin. Hooper, D.C., Wolfson, J.S., Ng, E.Y., Swartz, M.N. Am. J. Med. (1987) [Pubmed]
  18. Control of segregation of chromosomal DNA by sex factor F in Escherichia coli. Mutants of DNA gyrase subunit A suppress letD (ccdB) product growth inhibition. Miki, T., Park, J.A., Nagao, K., Murayama, N., Horiuchi, T. J. Mol. Biol. (1992) [Pubmed]
  19. Role of mutations in DNA gyrase genes in ciprofloxacin resistance of Pseudomonas aeruginosa susceptible or resistant to imipenem. Cambau, E., Perani, E., Dib, C., Petinon, C., Trias, J., Jarlier, V. Antimicrob. Agents Chemother. (1995) [Pubmed]
  20. Influence of recA mutations on gyrA dependent quinolone resistance. Urios, A., Herrera, G., Aleixandre, V., Blanco, M. Biochimie (1991) [Pubmed]
  21. DNA supercoiling in Escherichia coli: topA mutations can be suppressed by DNA amplifications involving the tolC locus. Dorman, C.J., Lynch, A.S., Bhriain, N.N., Higgins, C.F. Mol. Microbiol. (1989) [Pubmed]
  22. ParC subunit of DNA topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype. Muñoz, R., De La Campa, A.G. Antimicrob. Agents Chemother. (1996) [Pubmed]
  23. Sequence analysis, purification, and study of inhibition by 4-quinolones of the DNA gyrase from Mycobacterium smegmatis. Revel-Viravau, V., Truong, Q.C., Moreau, N., Jarlier, V., Sougakoff, W. Antimicrob. Agents Chemother. (1996) [Pubmed]
  24. The expression of Escherichia coli SOS genes recA and uvrA is inducible by polyamines. Oh, T.J., Kim, I.G. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  25. Molecular basis of quinolone resistance in Escherichia coli from wild birds. Jiménez Gómez, P.A., García de los Rios, J.E., Rojas Mendoza, A., de Pedro Ramonet, P., García Albiach, R., Reche Sainz, M.P. Can. J. Vet. Res. (2004) [Pubmed]
  26. Incidence and mechanism of ciprofloxacin resistance in Campylobacter spp. isolated from commercial poultry flocks in the United Kingdom before, during, and after fluoroquinolone treatment. Griggs, D.J., Johnson, M.M., Frost, J.A., Humphrey, T., Jørgensen, F., Piddock, L.J. Antimicrob. Agents Chemother. (2005) [Pubmed]
  27. Molecular epidemiology and mutations at gyrA and parC genes of ciprofloxacin-resistant Escherichia coli isolates from a Taiwan medical center. Chen, J.Y., Siu, L.K., Chen, Y.H., Lu, P.L., Ho, M., Peng, C.F. Microb. Drug Resist. (2001) [Pubmed]
  28. Crystallization and preliminary X-ray crystallographic studies on the parD-encoded protein Kid from Escherichia coli plasmid R1. Hargreaves, D., Giraldo, R., Santos-Sierra, S., Boelens, R., Rice, D.W., Díaz Orejas, R., Rafferty, J.B. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
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