dna topoisomerase iv


Summary: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Topoisomerase IV binds to DNA as a heterotetramer consisting 2 parC and 2 parE subunits. Topoisomerase IV is a decatenating enzyme that resolves interlinked daughter chromosomes following DNA replication.

Top Publications

  1. Hopkins K, Davies R, Threlfall E. Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments. Int J Antimicrob Agents. 2005;25:358-73 pubmed
  2. De Vecchi E, Nicola L, Ossola F, Drago L. In vitro selection of resistance in Streptococcus pneumoniae at in vivo fluoroquinolone concentrations. J Antimicrob Chemother. 2009;63:721-7 pubmed publisher
    ..Levofloxacin and moxifloxacin are characterized by a lower propensity to select in vitro for resistance in S. pneumoniae than ciprofloxacin and prulifloxacin, when tested at plasma and lung concentrations. ..
  3. Lee I, Dong K, Berger J. The role of DNA bending in type IIA topoisomerase function. Nucleic Acids Res. 2013;41:5444-56 pubmed publisher
    ..These data show that DNA binding and bending by topo IV can be uncoupled, and indicate that the stabilization of a highly curved DNA geometry is critical to the type IIA topoisomerase catalytic cycle. ..
  4. Lautenbach E, Fishman N, Metlay J, Mao X, Bilker W, Tolomeo P, et al. Phenotypic and genotypic characterization of fecal Escherichia coli isolates with decreased susceptibility to fluoroquinolones: results from a large hospital-based surveillance initiative. J Infect Dis. 2006;194:79-85 pubmed
    ..Resistance to nalidixic acid may be useful in the identification of E. coli with early resistance mutations. ..
  5. Wohlkonig A, Chan P, Fosberry A, Homes P, Huang J, Kranz M, et al. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat Struct Mol Biol. 2010;17:1152-3 pubmed publisher
    ..This provides a molecular basis for the quinolone inhibition mechanism, resistance mutations and invariant quinolone antibacterial structural features. ..
  6. Turner A, Nair S, Wain J. The acquisition of full fluoroquinolone resistance in Salmonella Typhi by accumulation of point mutations in the topoisomerase targets. J Antimicrob Chemother. 2006;58:733-40 pubmed
    ..These results predict that the use of ofloxacin or ciprofloxacin will select for resistance to gatifloxacin in nature. ..
  7. Chang T, Lu P, Li H, Chang C, Chen T, Chang L. Characterization of fluoroquinolone resistance mechanisms and their correlation with the degree of resistance to clinically used fluoroquinolones among Escherichia coli isolates. J Chemother. 2007;19:488-94 pubmed
    ..In conclusion, mutations in the QRDR are the primary mechanism for increasing fluoroquinolone resistance, and in combination with efflux pump over-expression, contribute to high-level resistance. ..
  8. Bellon S, Parsons J, Wei Y, Hayakawa K, Swenson L, Charifson P, et al. Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase. Antimicrob Agents Chemother. 2004;48:1856-64 pubmed
    ..These data demonstrate that the ParE M74 and GyrB I78 side chains impart opposite effects on the enzyme's substrate affinity and catalytic efficiency. ..
  9. Grainge I, Bregu M, Vazquez M, Sivanathan V, Ip S, Sherratt D. Unlinking chromosome catenanes in vivo by site-specific recombination. EMBO J. 2007;26:4228-38 pubmed
    ..We conclude that FtsK acts in vivo to simplify chromosomal topology as Xer recombination interconverts monomeric and dimeric chromosomes. ..

More Information


  1. Chau T, Campbell J, Galindo C, Van Minh Hoang N, Diep T, Nga T, et al. Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother. 2007;51:4315-23 pubmed
    ..The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions. ..
  2. Cambau E, Matrat S, Pan X, Roth Dit Bettoni R, Corbel C, Aubry A, et al. Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. J Antimicrob Chemother. 2009;63:443-50 pubmed publisher
    ..aureus and S. pneumoniae. ..
  3. Mendez Arancibia E, Pitart C, Ruiz J, Marco F, Gascon J, Vila J. Evolution of antimicrobial resistance in enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli causing traveller's diarrhoea. J Antimicrob Chemother. 2009;64:343-7 pubmed publisher
    ..These agents should therefore be used with caution in patients with traveller's diarrhoea returning from these geographical areas. ..
  4. Korzheva N, Davies T, Goldschmidt R. Novel Ser79Leu and Ser81Ile substitutions in the quinolone resistance-determining regions of ParC topoisomerase IV and GyrA DNA gyrase subunits from recent fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates. Antimicrob Agents Chemother. 2005;49:2479-86 pubmed
  5. Alt S, Mitchenall L, Maxwell A, Heide L. Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibiotics. J Antimicrob Chemother. 2011;66:2061-9 pubmed publisher
    ..occurring aminocoumarin antibiotics and six structural analogues (novclobiocins) against DNA gyrase and DNA topoisomerase IV from Escherichia coli and Staphylococcus aureus as well as the effect of potassium and sodium glutamate on ..
  6. Arnoldi E, Pan X, Fisher L. Functional determinants of gate-DNA selection and cleavage by bacterial type II topoisomerases. Nucleic Acids Res. 2013;41:9411-23 pubmed publisher
  7. Oblak M, Kotnik M, Solmajer T. Discovery and development of ATPase inhibitors of DNA gyrase as antibacterial agents. Curr Med Chem. 2007;14:2033-47 pubmed
    ..This review summarizes the discovery of ATPase inhibitors of DNA gyrase B in the last decade and their development as potential antibacterial agents. ..
  8. Laponogov I, Pan X, Veselkov D, McAuley K, Fisher L, Sanderson M. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS ONE. 2010;5:e11338 pubmed publisher
  9. Laponogov I, Veselkov D, Sohi M, Pan X, Achari A, Yang C, et al. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target. PLoS ONE. 2007;2:e301 pubmed
    ..These features may account for the unique DNA recognition and quinolone targeting properties of pneumococcal type II topoisomerases compared to their gram-negative counterparts. ..
  10. Chenia H, Pillay B, Pillay D. Analysis of the mechanisms of fluoroquinolone resistance in urinary tract pathogens. J Antimicrob Chemother. 2006;58:1274-8 pubmed
    ..8% of isolates. A combination of target gene alterations, altered OM permeability, presence of the qnrA gene and active efflux appear to act together to produce a high-level, multiresistance phenotype. ..
  11. Strahilevitz J, Hooper D. Dual targeting of topoisomerase IV and gyrase to reduce mutant selection: direct testing of the paradigm by using WCK-1734, a new fluoroquinolone, and ciprofloxacin. Antimicrob Agents Chemother. 2005;49:1949-56 pubmed
    ..By use of a combination of differentially targeting quinolones, this study provides novel data in direct support of the paradigm for dual targeting of quinolone action and reduced development of resistance. ..
  12. Charvin G, Strick T, Bensimon D, Croquette V. Tracking topoisomerase activity at the single-molecule level. Annu Rev Biophys Biomol Struct. 2005;34:201-19 pubmed
    ..These results shed new light on the mechanism of these enzymes and their function in vivo. ..
  13. Corbett K, Schoeffler A, Thomsen N, Berger J. The structural basis for substrate specificity in DNA topoisomerase IV. J Mol Biol. 2005;351:545-61 pubmed
    ..These findings in turn explain how the structures and functions of bacterial type IIA topoisomerases have evolved to meet specific needs of different bacterial families for the control of chromosome superstructure. ..
  14. Eaves D, Randall L, Gray D, Buckley A, Woodward M, White A, et al. Prevalence of mutations within the quinolone resistance-determining region of gyrA, gyrB, parC, and parE and association with antibiotic resistance in quinolone-resistant Salmonella enterica. Antimicrob Agents Chemother. 2004;48:4012-5 pubmed
    ..Although it is counterintuitive, isolates with a mutation in both gyrA and parC were more susceptible to ciprofloxacin than were isolates with a mutation in gyrA alone. ..
  15. Touyama M, Higa F, Nakasone C, Shinzato T, Akamine M, Haranaga S, et al. In vitro activity of sitafloxacin against clinical strains of Streptococcus pneumoniae with defined amino acid substitutions in QRDRs of gyrase A and topoisomerase IV. J Antimicrob Chemother. 2006;58:1279-82 pubmed
    ..016-0.5 mg/L. These findings warrant further studies to evaluate the usefulness of sitafloxacin in the treatment of levofloxacin-resistant S. pneumoniae infection. ..
  16. Grohs P, Podglajen I, Gutmann L. Activities of different fluoroquinolones against Bacillus anthracis mutants selected in vitro and harboring topoisomerase mutations. Antimicrob Agents Chemother. 2004;48:3024-7 pubmed
    ..Among the fluoroquinolones tested, garenoxacin showed the best activity. ..
  17. Pan X, Gould K, Fisher L. Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV. Antimicrob Agents Chemother. 2009;53:3822-31 pubmed publisher
    ..It appears that PD 0305970 interacts uniquely to stabilize the cleavage complex of gyrase/topo IV perhaps via an altered orientation directed by the bidentate 3-amino-2,4-dione moiety. ..
  18. Richter S, Heilmann K, Beekmann S, Miller N, Rice C, Doern G. The molecular epidemiology of Streptococcus pneumoniae with quinolone resistance mutations. Clin Infect Dis. 2005;40:225-35 pubmed
    ..pneumoniae in the United States has increased but remains genetically diverse. However, 35% of LNSP were related to widespread pneumococcal clones, increasing the potential for the rapid spread of quinolone resistance in this species. ..
  19. Kim H, Park C, Kim C, Kim E, Jacoby G, Hooper D. Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year period. Antimicrob Agents Chemother. 2009;53:639-45 pubmed publisher
  20. Namboodiri S, Opintan J, Lijek R, Newman M, Okeke I. Quinolone resistance in Escherichia coli from Accra, Ghana. BMC Microbiol. 2011;11:44 pubmed publisher
    ..Containment strategies to limit the spread of quinolone-resistant E. coli need to be deployed to conserve quinolone effectiveness and promote alternatives to their use. ..
  21. Randall L, Coldham N, Woodward M. Detection of mutations in Salmonella enterica gyrA, gyrB, parC and parE genes by denaturing high performance liquid chromatography (DHPLC) using standard HPLC instrumentation. J Antimicrob Chemother. 2005;56:619-23 pubmed
    ..The results demonstrated that a non-specialist standard HPLC machine fitted with a generally available column can be used to detect SNPs in gyrA, gyrB, parC and parE genes by DHPLC. Wider applications should be possible. ..
  22. Lesterlin C, Gigant E, Boccard F, Espeli O. Sister chromatid interactions in bacteria revealed by a site-specific recombination assay. EMBO J. 2012;31:3468-79 pubmed publisher
    ..The frequency of sister chromatid interactions were modulated by the activity of Topo-IV, revealing that DNA topology modulates cohesion at the molecular scale in bacteria. ..
  23. Aubry A, Fisher L, Jarlier V, Cambau E. First functional characterization of a singly expressed bacterial type II topoisomerase: the enzyme from Mycobacterium tuberculosis. Biochem Biophys Res Commun. 2006;348:158-65 pubmed
    ..coli gyrase. Overall, the type II topoisomerase of M. tuberculosis exhibits classical polyvalent activities of DNA gyrase for supercoiling but enhanced relaxation, cleavage, and decatenation activities. ..
  24. Ellsworth E, Tran T, Showalter H, Sanchez J, Watson B, Stier M, et al. 3-aminoquinazolinediones as a new class of antibacterial agents demonstrating excellent antibacterial activity against wild-type and multidrug resistant organisms. J Med Chem. 2006;49:6435-8 pubmed
    ..These agents also demonstrate in vivo efficacy in murine systemic infection models. ..
  25. Davies T, Yee Y, Goldschmidt R, Bush K, Sahm D, Evangelista A. Infrequent occurrence of single mutations in topoisomerase IV and DNA gyrase genes among US levofloxacin-susceptible clinical isolates of Streptococcus pneumoniae from nine institutions (1999-2003). J Antimicrob Chemother. 2006;57:437-42 pubmed
    ..Overall prevalence of single QRDR mutations in levofloxacin-susceptible S. pneumoniae with MICs of < or = 2 mg/L was 0.4% (4/1106) and has remained <1% within nine institutions over 5 years (1999-2003). ..
  26. Oppegard L, Streck K, Rosen J, Schwanz H, Drlica K, Kerns R, et al. Comparison of in vitro activities of fluoroquinolone-like 2,4- and 1,3-diones. Antimicrob Agents Chemother. 2010;54:3011-4 pubmed publisher
    ..aureus. ..
  27. Richter S, Leo E, Giaretta G, Gatto B, Fisher L, Palumbo M. Clerocidin interacts with the cleavage complex of Streptococcus pneumoniae topoisomerase IV to induce selective irreversible DNA damage. Nucleic Acids Res. 2006;34:1982-91 pubmed
    ..The unique ability to form exclusively irreversible DNA breaks suggests topoisomerase IV may be a key intracellular target of CL in bacteria. ..
  28. Robertson G, Bonventre E, Doyle T, Du Q, Duncan L, Morris T, et al. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus. Antimicrob Agents Chemother. 2008;52:2313-23 pubmed publisher
    ..potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant...
  29. Briales A, Rodríguez Martínez J, Velasco C, Díaz de Alba P, Domínguez Herrera J, Pachon J, et al. In vitro effect of qnrA1, qnrB1, and qnrS1 genes on fluoroquinolone activity against isogenic Escherichia coli isolates with mutations in gyrA and parC. Antimicrob Agents Chemother. 2011;55:1266-9 pubmed publisher
    ..coli that harbored a Ser83Leu substitution in GyrA increased mutant prevention concentration (MPC) values to 8 to 32 ?g/ml. qnr gene expression in E. coli may play an important role in selecting for one-step FQ-resistant mutants. ..
  30. Morgan Linnell S, Becnel Boyd L, Steffen D, Zechiedrich L. Mechanisms accounting for fluoroquinolone resistance in Escherichia coli clinical isolates. Antimicrob Agents Chemother. 2009;53:235-41 pubmed publisher
    ..Thus, additional, unknown fluoroquinolone resistance mechanisms must be present in some clinical isolates. ..
  31. Ruthenburg A, Graybosch D, Huetsch J, Verdine G. A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias. J Biol Chem. 2005;280:26177-84 pubmed
    ..We propose a model wherein the right-handed ((+) solenoidal) wrapping of DNA around the E. coli GyrA-CTD enforces unidirectional (-) DNA supercoiling. ..
  32. Leo E, Gould K, Pan X, Capranico G, Sanderson M, Palumbo M, et al. Novel symmetric and asymmetric DNA scission determinants for Streptococcus pneumoniae topoisomerase IV and gyrase are clustered at the DNA breakage site. J Biol Chem. 2005;280:14252-63 pubmed
    ..However, both pneumococcal enzymes cleaved an E. coli gyrase site suggesting overlap in gyrase determinants. We propose a model for the cleavage complex of topo IV/gyrase that accommodates the unique -2A/+6T and other preferences. ..
  33. Jacoby G. Mechanisms of resistance to quinolones. Clin Infect Dis. 2005;41 Suppl 2:S120-6 pubmed
    ..Although Qnr by itself produces only low-level resistance, its presence facilitates the selection of higher-level resistance mutations, thus contributing to the alarming increase in resistance to quinolones. ..
  34. Hsieh T, Farh L, Huang W, Chan N. Structure of the topoisomerase IV C-terminal domain: a broken beta-propeller implies a role as geometry facilitator in catalysis. J Biol Chem. 2004;279:55587-93 pubmed
    ..The possible role of ParC-CTD as a geometry facilitator during various catalytic events and the evolutionary relationships between prokaryotic type IIA Topos have also been discussed according to these new structural insights. ..
  35. Hayama R, Marians K. Physical and functional interaction between the condensin MukB and the decatenase topoisomerase IV in Escherichia coli. Proc Natl Acad Sci U S A. 2010;107:18826-31 pubmed publisher
    ..We show that MukB stimulates the superhelical DNA relaxation activity of wild-type Topo IV, but not that of Topo IV reconstituted with ParC R705E R729A. ..
  36. Couzinet S, Yugueros J, Barras C, Visomblin N, Francois P, Lacroix B, et al. Evaluation of a high-density oligonucleotide array for characterization of grlA, grlB, gyrA and gyrB mutations in fluoroquinolone resistant Staphylococcus aureus isolates. J Microbiol Methods. 2005;60:275-9 pubmed
    ..For the two most important genes, gyrA and grlA, correlation with sequencing reached 95.1%. If all genes were considered, correlation was 88.8%. ..
  37. Laponogov I, Sohi M, Veselkov D, Pan X, Sawhney R, Thompson A, et al. Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nat Struct Mol Biol. 2009;16:667-9 pubmed publisher
    ..These structures reveal two drug molecules intercalated at the highly bent DNA gate and help explain antibacterial quinolone action and resistance. ..
  38. Lin C, Chen T, Wang Y, Chang C, Hsuan S, Chang Y, et al. Analysis of ciprofloxacin-resistant Salmonella strains from swine, chicken, and their carcasses in Taiwan and detection of parC resistance mutations by a mismatch amplification mutation assay PCR. J Food Prot. 2009;72:14-20 pubmed
    ..MAMA-PCR targeting parC could provide a fast method for those laboratories interested in quickly characterizing the resistance profile and with little access to DNA sequencing facilities. ..
  39. Dimitrov T, Dashti A, Albaksami O, Udo E, Jadaon M, Albert M. Ciprofloxacin-resistant Salmonella enterica serovar typhi from Kuwait with novel mutations in gyrA and parC genes. J Clin Microbiol. 2009;47:208-11 pubmed publisher
    ..Both isolates had three novel gyrA mutations (55-Leu-->Trp, 87-Asp-->Ala, and 106-Gln-->Arg) and three novel parC mutations (84-Glu-->Lys, 106-Trp-->Gly, and 128-Tyr-->Asp). ..
  40. Wang X, Reyes Lamothe R, Sherratt D. Modulation of Escherichia coli sister chromosome cohesion by topoisomerase IV. Genes Dev. 2008;22:2426-33 pubmed publisher
    ..Therefore, we propose that precatenanes, which form as replication progresses by interwinding of newly replicated sister chromosomes, are responsible for E. coli sister chromosome cohesion...
  41. Orscheln R, Johnson D, Olson S, Presti R, Martin J, Kaplan E, et al. Intrinsic reduced susceptibility of serotype 6 Streptococcus pyogenes to fluoroquinolone antibiotics. J Infect Dis. 2005;191:1272-9 pubmed
    ..This finding was also demonstrated in erythromycin-resistant M/emm type 6 S. pyogenes, which raises concern for the emergence of multidrug-resistant S. pyogenes. ..
  42. Charvin G, Strick T, Bensimon D, Croquette V. Topoisomerase IV bends and overtwists DNA upon binding. Biophys J. 2005;89:384-92 pubmed
    ..89 and a strongly bound state (with probability p = 0.11). The methodology introduced here to characterize the Topo IV/DNA complex is very general and could be used to study other DNA/protein complexes. ..
  43. Gaind R, Paglietti B, Murgia M, Dawar R, Uzzau S, Cappuccinelli P, et al. Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India. J Antimicrob Chemother. 2006;58:1139-44 pubmed
    ..To define the genetic characteristics and resistance mechanisms of clinical isolates of Salmonella enterica serovar Typhi (S. Typhi) and S. enterica serovar Paratyphi A (S. Paratyphi A) exhibiting high-level fluoroquinolones resistance...
  44. Doern G, Richter S, Miller A, Miller N, Rice C, Heilmann K, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes?. Clin Infect Dis. 2005;41:139-48 pubmed
    ..pneumoniae is becoming more prevalent. It appears that, as fluoroquinolone resistance emerges among S. pneumoniae in the United States, resistance to other antimicrobial classes is becoming less common. ..
  45. Sierra J, Cabeza J, Ruiz Chaler M, Montero T, Hernandez J, Mensa J, et al. The selection of resistance to and the mutagenicity of different fluoroquinolones in Staphylococcus aureus and Streptococcus pneumoniae. Clin Microbiol Infect. 2005;11:750-8 pubmed
  46. Lopez V, Martínez Robles M, Hernandez P, Krimer D, Schvartzman J. Topo IV is the topoisomerase that knots and unknots sister duplexes during DNA replication. Nucleic Acids Res. 2012;40:3563-73 pubmed publisher
    ..Under these conditions, Topo IV inadvertently makes the strand passages that lead to the formation of knots and removes them later on to allow their correct segregation. ..
  47. Li Y, Stewart N, Berger A, Vos S, Schoeffler A, Berger J, et al. Escherichia coli condensin MukB stimulates topoisomerase IV activity by a direct physical interaction. Proc Natl Acad Sci U S A. 2010;107:18832-7 pubmed publisher
  48. Sinha S, Chattopadhyay S, Bhattacharya S, Nair G, Ramamurthy T. An unusually high level of quinolone resistance associated with type II topoisomerase mutations in quinolone resistance-determining regions of Aeromonas caviae isolated from diarrhoeal patients. Res Microbiol. 2004;155:827-9 pubmed
    ..In resistant strains, double mutations (Ser(83)-->Ile and Asp(87)-->Asn) and a single mutation (Ser(80)-->Ile) were detected in the QRDR of gyrA and parC, respectively. ..
  49. Sissi C, Palumbo M. In front of and behind the replication fork: bacterial type IIA topoisomerases. Cell Mol Life Sci. 2010;67:2001-24 pubmed publisher
  50. Neuman K, Charvin G, Bensimon D, Croquette V. Mechanisms of chiral discrimination by topoisomerase IV. Proc Natl Acad Sci U S A. 2009;106:6986-91 pubmed publisher
    ..These results provide fresh insight into topoisomerase mechanisms and lead to a model that reconciles contradictory aspects of previous findings while providing a framework to interpret future results. ..
  51. Pokrovskaya V, Belakhov V, Hainrichson M, Yaron S, Baasov T. Design, synthesis, and evaluation of novel fluoroquinolone-aminoglycoside hybrid antibiotics. J Med Chem. 2009;52:2243-54 pubmed publisher
    ..Significant delay of resistance formation was observed in both E. coli and B. subtilis to the treatment with ciprofloxacin-neomycin hybrid in comparison to that of each drug separately or their 1:1 mixture. ..
  52. Richter S, Giaretta G, Comuzzi V, Leo E, Mitchenall L, Fisher L, et al. Hot-spot consensus of fluoroquinolone-mediated DNA cleavage by Gram-negative and Gram-positive type II DNA topoisomerases. Nucleic Acids Res. 2007;35:6075-85 pubmed
  53. Rozen D, McGee L, Levin B, Klugman K. Fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007;51:412-6 pubmed
    ..We discuss the implications of these results for the epidemiology of fluoroquinolone resistance and the evolution of acquired resistance in treated patients. ..
  54. Pitts S, Liou G, Mitchenall L, Burgin A, Maxwell A, Neuman K, et al. Use of divalent metal ions in the DNA cleavage reaction of topoisomerase IV. Nucleic Acids Res. 2011;39:4808-17 pubmed publisher
  55. Aldred K, McPherson S, Wang P, Kerns R, Graves D, Turnbough C, et al. Drug interactions with Bacillus anthracis topoisomerase IV: biochemical basis for quinolone action and resistance. Biochemistry. 2012;51:370-81 pubmed publisher
    ..Our findings provide an underlying biochemical basis for the ability of quinazolinediones to overcome clinically relevant quinolone resistance mutations in bacterial type II topoisomerases. ..
  56. Hopkins K, Arnold C, Threlfall E. Rapid detection of gyrA and parC mutations in quinolone-resistant Salmonella enterica using Pyrosequencing technology. J Microbiol Methods. 2007;68:163-71 pubmed
    ..The Pyrosequencing technology is a rapid and reliable alternative to current methods for identification of gyrA and parC mutations in S. enterica. ..
  57. Oh W, Suh J, Song J, Ko K, Jung S, Peck K, et al. Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae from Asian countries: ANSORP study. Microb Drug Resist. 2004;10:37-42 pubmed
    ..Data from PFGE suggest an introduction and local spread of multiple resistant Spain(23F)-1 clone in Hong Kong, but isolates from other Asian countries were not related to this clone. ..