Research Topics

Genomes and Genes

Species

dna gyrase

Summary

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. Gyrase binds to DNA as a heterotetramer consisting two A and two B subunits. In the presence of ATP, gyrase is able to convert relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.

Top Publications

  1. ncbi Mechanism of plasmid-mediated quinolone resistance
    John H Tran
    Infectious Disease Department, Lahey Clinic, Burlington, MA 01805, USA
    Proc Natl Acad Sci U S A 99:5638-42. 2002
  2. ncbi A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley and Fluidigm Corporation, South San Francisco, CA 94080, USA
    Nucleic Acids Res 38:7830-44. 2010
  3. ncbi Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing
    Ruiru Shi
    Mycobacterial Reference Center, The Research Institute of Tuberculosis, 3-1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan
    J Clin Microbiol 44:4566-8. 2006
  4. ncbi Fluoroquinolone resistance in Mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposure
    Jann Yuan Wang
    Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
    J Antimicrob Chemother 59:860-5. 2007
  5. ncbi Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments
    Katie L Hopkins
    Antimicrobial Resistance and Molecular Epidemiology Unit, Laboratory of Enteric Pathogens, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5HT, UK
    Int J Antimicrob Agents 25:358-73. 2005
  6. ncbi Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigation
    Guangsen Fu
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People s Republic of China
    Nucleic Acids Res 37:5908-16. 2009
  7. ncbi Nucleotide binding to DNA gyrase causes loss of DNA wrap
    Jonathan G Heddle
    Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK
    J Mol Biol 337:597-610. 2004
  8. ncbi Solution structures of DNA-bound gyrase
    Nicole M Baker
    Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA
    Nucleic Acids Res 39:755-66. 2011
  9. ncbi Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations
    H Wang
    Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China
    Antimicrob Agents Chemother 45:1515-21. 2001
  10. ncbi Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model
    Julien Poissy
    Laboratoire de Bacteriologie Hygiene, Faculte de Medecine, Pierre et Marie Curie Université Paris, 91 Boulevard de l Hopital, Paris Cedex 13, France
    Antimicrob Agents Chemother 54:4765-71. 2010

Research Grants

  1. Plasmid-Mediated Quinolone Resistance
    George A Jacoby; Fiscal Year: 2010
  2. Plasmid-Mediated Quinolone Resistance
    David Hooper; Fiscal Year: 2009
  3. QUINOLONE RESISTANCE MECHANISMS IN STAPHYLOCOCCUS AUREUS
    David Hooper; Fiscal Year: 2002
  4. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth N Kreuzer; Fiscal Year: 2010
  5. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth N Kreuzer; Fiscal Year: 2010
  6. PATHOBIOCHEMISTRY OF CHLAMYDIA TRACHOMONAS HUMAN SEXUALLY TRANSMITTED DISEASES
    BIBHUTI SINGH; Fiscal Year: 2001
  7. Modular Enzymatic Assembly Lines for Antibiotics
    Christopher Walsh; Fiscal Year: 2007
  8. ROLE OF TOPOISOMERASES IN DNA REPLICATION
    KENNETH MARIANS; Fiscal Year: 1990
  9. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN P HIGGINS; Fiscal Year: 2010
  10. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN HIGGINS; Fiscal Year: 2009

Detail Information

Publications281 found, 100 shown here

  1. ncbi Mechanism of plasmid-mediated quinolone resistance
    John H Tran
    Infectious Disease Department, Lahey Clinic, Burlington, MA 01805, USA
    Proc Natl Acad Sci U S A 99:5638-42. 2002
    Quinolones are potent antibacterial agents that specifically target bacterial DNA gyrase and topoisomerase IV. Widespread use of these agents has contributed to the rise of bacterial quinolone resistance...
  2. ncbi A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley and Fluidigm Corporation, South San Francisco, CA 94080, USA
    Nucleic Acids Res 38:7830-44. 2010
    ..Our data indicate that the insert has two functions, acting as a steric buttress to pre-configure the primary DNA-binding site, and serving as a relay that may help coordinate communication between different functional domains...
  3. ncbi Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing
    Ruiru Shi
    Mycobacterial Reference Center, The Research Institute of Tuberculosis, 3-1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan
    J Clin Microbiol 44:4566-8. 2006
    ..This is the first report to describe denaturing high-pressure liquid chromatography analysis of mutations in gyrA of M. tuberculosis in a large number of clinical isolates...
  4. ncbi Fluoroquinolone resistance in Mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposure
    Jann Yuan Wang
    Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
    J Antimicrob Chemother 59:860-5. 2007
    ..We assessed the fluoroquinolone (FQ) susceptibility of clinical isolates of Mycobacterium tuberculosis in an endemic area. The genetic mutations responsible for FQ resistance were also evaluated...
  5. ncbi Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments
    Katie L Hopkins
    Antimicrobial Resistance and Molecular Epidemiology Unit, Laboratory of Enteric Pathogens, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5HT, UK
    Int J Antimicrob Agents 25:358-73. 2005
    ....
  6. ncbi Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigation
    Guangsen Fu
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People s Republic of China
    Nucleic Acids Res 37:5908-16. 2009
    b>DNA gyrase is an indispensible marvelous molecular machine in manipulating the DNA topology for the prokaryotes...
  7. ncbi Nucleotide binding to DNA gyrase causes loss of DNA wrap
    Jonathan G Heddle
    Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK
    J Mol Biol 337:597-610. 2004
    b>DNA gyrase negatively supercoils DNA in a reaction coupled to the binding and hydrolysis of ATP. Limited supercoiling can be achieved in the presence of the non-hydrolysable ATP analogue, 5'-adenylyl beta,gamma-imidodiphosphate (ADPNP)...
  8. ncbi Solution structures of DNA-bound gyrase
    Nicole M Baker
    Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA
    Nucleic Acids Res 39:755-66. 2011
    The DNA gyrase negative supercoiling mechanism involves the assembly of a large gyrase/DNA complex and conformational rearrangements coupled to ATP hydrolysis...
  9. ncbi Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations
    H Wang
    Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China
    Antimicrob Agents Chemother 45:1515-21. 2001
    ..5- to 6-fold. This study shows that mutations in acrR are an additional genetic basis for fluoroquinolone resistance...
  10. ncbi Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model
    Julien Poissy
    Laboratoire de Bacteriologie Hygiene, Faculte de Medecine, Pierre et Marie Curie Université Paris, 91 Boulevard de l Hopital, Paris Cedex 13, France
    Antimicrob Agents Chemother 54:4765-71. 2010
    ..The extent of Mycobacterium tuberculosis resistance to fluoroquinolones depends on the mutation in the DNA gyrase, the only target of fluoroquinolones. The MIC of moxifloxacin, the most active fluoroquinolone against M...
  11. ncbi An open conformation of the Thermus thermophilus gyrase B ATP-binding domain
    Valerie Lamour
    Institut de Génétique et de Biologie Moléculaire, CNRS INSERM ULP, BP163, 1 rue Laurent Fries, 67404 Illkirch Cedex, France
    J Biol Chem 277:18947-53. 2002
    b>DNA gyrase forms an A(2)B(2) tetramer involved in DNA replication, repair, recombination, and transcription in which the B subunit catalyzes ATP hydrolysis...
  12. ncbi The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects on DNA gyrase catalytic reactions and on the ternary gyrase-DNA-quinolone complex
    Audrey Merens
    Universite Paris, IFR, Bacteriologie, Creteil, France
    J Bacteriol 191:1587-94. 2009
    MfpA(Mt) and QnrB4 are two newly characterized pentapeptide repeat proteins (PRPs) that interact with DNA gyrase. The mfpA(Mt) gene is chromosome borne in Mycobacterium tuberculosis, while qnrB4 is plasmid borne in enterobacteria...
  13. ncbi Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment
    Silke Feuerriegel
    Research Center Borstel, National Reference Center for Mycobacteria, Parkallee 18, 23845 Borstel, Germany
    Antimicrob Agents Chemother 53:3353-6. 2009
    ..The mechanisms that confer amikacin resistance in this setting remain unclear...
  14. ncbi Importance of the efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid
    I Escribano
    Section of Microbiology, Hospital General Universitario de Elche, Universidad Miguel Hernandez, Elche, Spain
    Chemotherapy 53:397-401. 2007
    ..Our aim was to study the influence of efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid...
  15. ncbi Simocyclinone D8, an inhibitor of DNA gyrase with a novel mode of action
    Ruth H Flatman
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK
    Antimicrob Agents Chemother 49:1093-100. 2005
    We have characterized the interaction of a new class of antibiotics, simocyclinones, with bacterial DNA gyrase. Even though their structures include an aminocoumarin moiety, a key feature of novobiocin, coumermycin A(1), and clorobiocin, ..
  16. ncbi Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase
    Jérémie Piton
    Unité de Dynamique Structurale des Macromolécules, Departement de Biologie Structurale et Chimie, Institut Pasteur, Paris, France
    PLoS ONE 5:e12245. 2010
    Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug ..
  17. ncbi A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase
    Marcus J Edwards
    Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK
    Science 326:1415-8. 2009
    Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme...
  18. ncbi The DNA-gate of Bacillus subtilis gyrase is predominantly in the closed conformation during the DNA supercoiling reaction
    Airat Gubaev
    Biozentrum, Department of Biophysical Chemistry, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland
    Proc Natl Acad Sci U S A 106:13278-83. 2009
    ..During the relaxation and supercoiling reactions, gyrase with an open DNA-gate is not significantly populated, consistent with gate-opening as a very rare event that only occurs briefly to allow for strand passage...
  19. ncbi Molecular characterization of ofloxacin-resistant Mycobacterium tuberculosis strains from Russia
    Igor Mokrousov
    Laboratory of Molecular Microbiology, St Petersburg Pasteur Institute, 197101 St Petersburg, Russia
    Antimicrob Agents Chemother 52:2937-9. 2008
    ..tuberculosis...
  20. ncbi Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque
    Marcelo Nollmann
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Nat Struct Mol Biol 14:264-71. 2007
    E. coli DNA gyrase uses the energy of ATP hydrolysis to introduce essential negative supercoils into the genome, thereby working against the mechanical stresses that accumulate in supercoiled DNA...
  21. ncbi Structural and biochemical analysis of the pentapeptide repeat protein EfsQnr, a potent DNA gyrase inhibitor
    Subray S Hegde
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Antimicrob Agents Chemother 55:110-7. 2011
    ..EfsQnr was cloned with an N-terminal 6× His tag and purified to homogeneity. EfsQnr partially protected DNA gyrase from fluoroquinolone inhibition at concentrations as low as 20 nM...
  22. ncbi The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode of inhibition
    J G Heddle
    Department of Biochemistry, University of Leicester, Leicester, LE1 7RH, UK
    J Mol Biol 307:1223-34. 2001
    Microcin B17 is a 3.1-kDa bactericidal peptide; the putative target of this antibiotic is DNA gyrase. Microcin B17 has no detectable effect on gyrase-catalysed DNA supercoiling or relaxation activities in vitro and is unable to stabilise ..
  23. ncbi YacG from Escherichia coli is a specific endogenous inhibitor of DNA gyrase
    Sugopa Sengupta
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
    Nucleic Acids Res 36:4310-6. 2008
    ..YacG was predicted to be a part of DNA gyrase interactome based on protein-protein interaction network...
  24. ncbi Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in a Taiwanese medical centre: 1995-2003
    Tsi-Shu Huang
    Section of Microbiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
    J Antimicrob Chemother 56:1058-62. 2005
    ..The emergence of fluoroquinolone resistance among MDR strains reinforces the need for routine fluoroquinolone susceptibility testing whenever these drugs might be used...
  25. ncbi Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering
    Lionel Costenaro
    Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom
    Structure 15:329-39. 2007
    b>DNA gyrase, the only topoisomerase able to introduce negative supercoils into DNA, is essential for bacterial transcription and replication; absent from humans, it is a successful target for antibacterials...
  26. ncbi Mechanisms of quinolone action and microbial response
    Peter M Hawkey
    Public Health Laboratory, Heartlands Hospital, Bordesley Green East, Birmingham B5 9SS, UK
    J Antimicrob Chemother 51:29-35. 2003
    ..However, it is conceivable that in the future, horizontal gene transfer may become a more important means of conferring resistance to fluoroquinolones...
  27. ncbi Fluoroquinolone resistance detection in Mycobacterium tuberculosis with locked nucleic acid probe real-time PCR
    H R van Doorn
    Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    Int J Tuberc Lung Dis 12:736-42. 2008
    ..Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases, Ho Chi Minh City, Vietnam...
  28. ncbi A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA
    Subray S Hegde
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Science 308:1480-3. 2005
    ..This protein binds to DNA gyrase and inhibits its activity...
  29. ncbi Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis: functional analysis of mutant enzymes
    Alexandra Aubry
    Molecular Genetics Group, Molecular and Metabolic Signaling Centre, Division of Basic Medical Scinces, St George s, University of London, United Kingdom
    Antimicrob Agents Chemother 50:104-12. 2006
    Mutations in the DNA gyrase GyrA2GyrB2 complex are associated with resistance to quinolones in Mycobacterium tuberculosis...
  30. ncbi Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones
    L Ferrero
    Departement des Biotechnologies, Rhone Poulenc Rorer S A, Centre de Recherche de Vitry Alfortville, Vitry sur Seine, France
    Mol Microbiol 13:641-53. 1994
    A 4.6 kb Staphylococcus aureus DNA fragment containing DNA gyrase-like genes (grlA and grlB) was cloned and sequenced. The proteins GrlA and GrlB exhibit more than 30% identity with E...
  31. ncbi In vivo and in vitro patterns of the activity of simocyclinone D8, an angucyclinone antibiotic from Streptomyces antibioticus
    Lisa M Oppegard
    Department of Pharmacology, University of Minnesota Medical School Twin Cities, 6 120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA
    Antimicrob Agents Chemother 53:2110-9. 2009
    ..Unlike quinolone treatment, however, SD8 treatment does not induce the SOS response. These results suggest that DNA gyrase is the target of SD8 in both gram-positive and gram-negative bacteria and that the lack of the antibacterial ..
  32. ncbi Fluoroquinolone resistance in Mycobacterium tuberculosis and mutations in gyrA and gyrB
    Andrea von Groll
    Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium
    Antimicrob Agents Chemother 53:4498-500. 2009
    ..Forty strains shared the same resistance results for the three fluoroquinolones. However, one strain, with an Asn-533 --> Thr mutation in gyrB, was susceptible to ofloxacin but resistant to moxifloxacin and gatifloxacin...
  33. ncbi Comparison of gyrA gene mutations between laboratory-selected ofloxacin-resistant Mycobacterium tuberculosis strains and clinical isolates
    Zhaogang Sun
    Department of Bacteriology and Immunology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou District, Beijing 101149, China
    Int J Antimicrob Agents 31:115-21. 2008
    ....
  34. ncbi Quinolone-resistant Haemophilus influenzae: determination of mutant selection window for ciprofloxacin, garenoxacin, levofloxacin, and moxifloxacin
    Xinying Li
    Public Health Research Institute, 225 Warren St, Newark, NJ 07103, USA
    Antimicrob Agents Chemother 48:4460-2. 2004
    ..Successive mutations raised the mutant selection window. The wild-type selection window for garenoxacin, levofloxacin, and moxifloxacin was also measured...
  35. ncbi Dimerization of Escherichia coli DNA-gyrase B provides a structural mechanism for activating the ATPase catalytic center
    L Brino
    Institut de Genetique et de Biologie Moleculaire et Cellulaire IGBMC, CNRS INSERM, Universite Louis Pasteur, BP 163, 1 rue Laurent Fries, 67404 Illkirch Cedex, France
    J Biol Chem 275:9468-75. 2000
    ....
  36. ncbi Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage
    Xiao Su Pan
    Molecular Genetics Group, Molecular and Metabolic Signalling Centre, Division of Basic Medical Sciences, St George s, University of London, Cranmer Terrace, London, SW17 0RE, UK
    Nucleic Acids Res 36:5516-29. 2008
    ..The molecular basis of CL action is poorly understood. We establish by genetic means that CL targets DNA gyrase in the gram-positive bacterium Streptococcus pneumoniae, and promotes gyrase-dependent single- and double-..
  37. ncbi Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase IV inhibitors obtained by combinatorial biosynthesis
    Ruth H Flatman
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich, NR4 7UH, United Kingdom
    Antimicrob Agents Chemother 50:1136-42. 2006
    ..This is the first report of a systematic evaluation of a series of aminocoumarins against both gyrase and topo IV. The results give further insight into the structure-activity relationships of aminocoumarin antibiotics...
  38. ncbi In vitro and in vivo activities of PD 0305970 and PD 0326448, new bacterial gyrase/topoisomerase inhibitors with potent antibacterial activities versus multidrug-resistant gram-positive and fastidious organism groups
    Michael D Huband
    Department of Antibacterial Biology, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
    Antimicrob Agents Chemother 51:1191-201. 2007
    ..7 mg/kg, respectively). PD 0305970 was also potent in a pneumococcal pneumonia mouse infection model (PD50=3.2 mg/kg) and was 22-fold more potent than levofloxacin...
  39. ncbi New antibacterial agents derived from the DNA gyrase inhibitor cyclothialidine
    Peter Angehrn
    F. Hoffmann-La Roche Ltd, Pharmaceutical Division, Preclinical Research, CH-4070 Basel, Switzerland
    J Med Chem 47:1487-513. 2004
    Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products...
  40. ncbi Interplay of DNA supercoiling and catenation during the segregation of sister duplexes
    María Luisa Martínez-Robles
    Departamento de Biologia Celular y del Desarrollo, Centro de Investigaciones Biologicas CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain
    Nucleic Acids Res 37:5126-37. 2009
    ..simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules...
  41. ncbi Monoclonal antibodies to mycobacterial DNA gyrase A inhibit DNA supercoiling activity
    U H Manjunatha
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
    Eur J Biochem 268:2038-46. 2001
    b>DNA gyrase is an essential type II topoisomerase found in bacteria. We have previously characterized DNA gyrase from Mycobacterium tuberculosis and Mycobacterium smegmatis...
  42. ncbi High-level fluoroquinolone resistance in Pseudomonas aeruginosa due to interplay of the MexAB-OprM efflux pump and the DNA gyrase mutation
    Akira Nakajima
    Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan
    Microbiol Immunol 46:391-5. 2002
    ..aeruginosa is mainly attributable to the constitutive expression of the xenobiotic efflux pump and mutation in DNA gyrase or topoisomerase IV...
  43. ncbi 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
    Sachin S Bhagwat
    Wockhardt Research Centre, D-4, Chikalthana, MIDC Area, 431210, Aurangabad (MS, India
    Antimicrob Agents Chemother 50:3568-79. 2006
    ..There was a twofold increase in the MICs of WCK 771 for single gyrA mutants, indicating that DNA gyrase is its primary target...
  44. ncbi Moonlighting function of glutamate racemase from Mycobacterium tuberculosis: racemization and DNA gyrase inhibition are two independent activities of the enzyme
    Sugopa Sengupta
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
    Microbiology 154:2796-803. 2008
    ..role in cell wall biosynthesis, MurI proteins from some bacteria have been shown to act as an inhibitor of DNA gyrase. Mycobacterium tuberculosis and Mycobacterium smegmatis MurI exhibit these dual characteristics...
  45. ncbi A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase II
    Thomas Gruger
    Department of Pharmaceutical Biology and Microbiology, Institute of Pharmacy, University of Hamburg, Germany
    Antimicrob Agents Chemother 48:4495-504. 2004
    ..Many fluoroquinolones are highly specific for bacterial type II topoisomerases and act against both DNA gyrase and topoisomerase IV...
  46. ncbi DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose
    Daniel Lafitte
    UMR CNRS 6032, UFR de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France
    Biochemistry 41:7217-23. 2002
    b>DNA gyrase is a major bacterial protein that is involved in replication and transcription and catalyzes the negative supercoiling of bacterial circular DNA...
  47. ncbi Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in Streptomyces antibioticus
    Tung B K Le
    Department of Molecular Microbiology, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
    Mol Microbiol 72:1462-74. 2009
    ..Simocyclinone D8 is a potent DNA gyrase inhibitor produced by Streptomyces antibioticus Tü 6040...
  48. ncbi 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
    Sutapa Sinha
    National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata 700 010, India
    Res Microbiol 155:827-9. 2004
    ..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. ncbi Development of a positive genetic selection system for inhibition of protein splicing using mycobacterial inteins in Escherichia coli DNA gyrase subunit A
    Eric Adam
    New England Biolabs, Beverly, MA 01915, USA
    J Mol Microbiol Biotechnol 4:479-87. 2002
    ..For example, pathogenic mycobacteria encode inteins that interrupt DNA gyrase. The gyrase selection system exploits (1) splicing of inteins out of Gyrase A and (2) the dominant lethal effect ..
  50. ncbi Active-site residues of Escherichia coli DNA gyrase required in coupling ATP hydrolysis to DNA supercoiling and amino acid substitutions leading to novobiocin resistance
    Christian H Gross
    Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA
    Antimicrob Agents Chemother 47:1037-46. 2003
    b>DNA gyrase is a bacterial type II topoisomerase which couples the free energy of ATP hydrolysis to the introduction of negative supercoils into DNA. Amino acids in proximity to bound nonhydrolyzable ATP analog (AMP...
  51. ncbi Differences in effects on DNA gyrase activity between two glutamate racemases of Bacillus subtilis, the poly-gamma-glutamate synthesis-linking Glr enzyme and the YrpC (MurI) isozyme
    Makoto Ashiuchi
    Department of Bioresources Science, Kochi University, Nankoku, Japan
    FEMS Microbiol Lett 223:221-5. 2003
    ..The YrpC isozyme, but not the Glr enzyme, was found to influence the activity of DNA gyrase, as did the MurI-type glutamate racemase of Escherichia coli, which is involved in peptidoglycan synthesis ..
  52. ncbi The action of the bacterial toxin microcin B17. Insight into the cleavage-religation reaction of DNA gyrase
    Olivier A Pierrat
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, United Kingdom
    J Biol Chem 278:35016-23. 2003
    We have examined the effects of the bacterial toxin microcin B17 (MccB17) on the reactions of Escherichia coli DNA gyrase. MccB17 slows down but does not completely inhibit the DNA supercoiling and relaxation reactions of gyrase...
  53. ncbi Relationship between mutations in the gyrA gene and quinolone resistance in clinical isolates of Corynebacterium striatum and Corynebacterium amycolatum
    Josep M Sierra
    Department of Microbiology, School of Medicine, , IDIBAPS, University of Barcelona, Barcelona, Spain
    Antimicrob Agents Chemother 49:1714-9. 2005
    ..amycolatum. Moreover, a PCR-RFLP-NcoI of the gyrA gene was developed to distinguish between C. amycolatum and C. striatum species...
  54. ncbi Inhibition of DNA gyrase activity by Mycobacterium smegmatis MurI
    Sugopa Sengupta
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
    FEMS Microbiol Lett 279:40-7. 2008
    ..enzymatic function, MurI from Escherichia coli, Bacillus subtilis and Mycobacterium tuberculosis inhibit DNA gyrase activity...
  55. ncbi Twisting of the DNA-binding surface by a beta-strand-bearing proline modulates DNA gyrase activity
    Tung Ju Hsieh
    Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City 100, Taiwan
    Nucleic Acids Res 38:4173-81. 2010
    b>DNA gyrase is the only topoisomerase capable of introducing (-) supercoils into relaxed DNA...
  56. ncbi Evidence for the role of DNA strand passage in the mechanism of action of microcin B17 on DNA gyrase
    Olivier A Pierrat
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, United Kingdom
    Biochemistry 44:4204-15. 2005
    Microcin B17 (MccB17) is a DNA gyrase poison; in previous work, this bacterial toxin was found to slowly and incompletely inhibit the reactions of supercoiling and relaxation of DNA by gyrase and to stabilize the cleavage complex, ..
  57. ncbi Novel multiplex allele-specific PCR assays for the detection of resistance to second-line drugs in Mycobacterium tuberculosis
    Joanna Evans
    Division of Medical Microbiology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
    J Antimicrob Chemother 65:897-900. 2010
    ..In this study, multiplex allele-specific (MAS)-PCR assays designed to detect the GyrA D94G and rrs A1401G mutations were evaluated for detection of ofloxacin and kanamycin resistance...
  58. ncbi Mapping simocyclinone D8 interaction with DNA gyrase: evidence for a new binding site on GyrB
    C Sissi
    Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, Padova 35131, Italy
    Antimicrob Agents Chemother 54:213-20. 2010
    ..To further characterize the mode of action of this antibiotic, we investigated its binding to the reconstituted DNA gyrase (A(2)B(2)) as well as to its GyrA and GyrB subunits and the individual domains of these proteins, by performing ..
  59. ncbi Vibrio cholerae ParE2 poisons DNA gyrase via a mechanism distinct from other gyrase inhibitors
    Jie Yuan
    Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, Tufts University School of Medicine, Boston, Massachusetts 02115, USA
    J Biol Chem 285:40397-408. 2010
    b>DNA gyrase is an essential bacterial enzyme required for the maintenance of chromosomal DNA topology...
  60. ncbi A monoclonal antibody that inhibits mycobacterial DNA gyrase by a novel mechanism
    Ujjini H Manjunatha
    Department of Microbiology and Cell Biology, Indian Institute of Science Bangalore, 560 012, India
    Nucleic Acids Res 33:3085-94. 2005
    b>DNA gyrase is a DNA topoisomerase indispensable for cellular functions in bacteria...
  61. ncbi Discovery and development of ATPase inhibitors of DNA gyrase as antibacterial agents
    Marko Oblak
    Lek Pharmaceuticals, D D, Drug Discovery, Ljubljana, Slovenia
    Curr Med Chem 14:2033-47. 2007
    b>DNA gyrase is an attractive and well established target for the development of antibacterial agents...
  62. ncbi Dissection of the nucleotide cycle of B. subtilis DNA gyrase and its modulation by DNA
    Thomas Göttler
    Division of Biophysical Chemistry, Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    J Mol Biol 367:1392-404. 2007
    ..While all type II DNA topoisomerases relax supercoiled DNA, DNA gyrase is the only enyzme that introduces negative supercoils into DNA at the expense of ATP hydrolysis...
  63. ncbi Mass spectrometry reveals that the antibiotic simocyclinone D8 binds to DNA gyrase in a "bent-over" conformation: evidence of positive cooperativity in binding
    Marcus J Edwards
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, United Kingdom
    Biochemistry 50:3432-40. 2011
    ..Here we present a mass spectrometry study of complexes formed between the A subunit of the topoisomerase DNA gyrase and the bifunctional inhibitor simocyclinone D8 (SD8), an antibiotic isolated from Streptomyces...
  64. ncbi The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin
    F T Tsai
    Laboratory of Molecular Biophysics, University of Oxford, United Kingdom
    Proteins 28:41-52. 1997
    ..Moreover, to understand the differences in energetics of binding of clorobiocin and novobiocin to the protein, the results from isothermal titration calorimetry are also presented...
  65. ncbi Mutation characterization of gyrA and gyrB genes in levofloxacin-resistant Mycobacterium tuberculosis clinical isolates from Guangdong Province in China
    Xiaomao Yin
    Institute for Pulmonary Disease, Guangzhou Chest Hospital, Yuexiu District, Guangzhou City, Guangdong Province, China
    J Infect 61:150-4. 2010
    ..The aim of this study was to observe the molecular characterization of gyrA and gyrB genes in FQ-resistant MTB clinical isolates from Guangdong Province in China...
  66. ncbi Evolution of antimicrobial resistance in enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli causing traveller's diarrhoea
    Eva Mendez Arancibia
    Department of Clinical Microbiology, Hospital Clinic, University of Barcelona, School of Medicine, Villarroel, 170, 08036 Barcelona, Spain
    J Antimicrob Chemother 64:343-7. 2009
    ..The aim of this study was to investigate the evolution of antimicrobial resistance in EAEC and ETEC causing diarrhoea in patients who had travelled to different developing countries, comparing two periods of time, 1994-97 and 2001-04...
  67. ncbi Mechanochemical analysis of DNA gyrase using rotor bead tracking
    Jeff Gore
    Department of Physics, University of California, Berkeley, California 94720, USA
    Nature 439:100-4. 2006
    b>DNA gyrase is a molecular machine that uses the energy of ATP hydrolysis to introduce essential negative supercoils into DNA...
  68. ncbi Energy coupling in type II topoisomerases: why do they hydrolyze ATP?
    Andrew D Bates
    School of Biological Sciences, University of Liverpool, UK bates liv ac uk
    Biochemistry 46:7929-41. 2007
    ..This review discusses our current understanding of the mechanisms behind the coupling of the energy of ATP hydrolysis to topological changes catalyzed by both of these classes of enzyme...
  69. ncbi Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection
    Joaquim Ruiz
    Department of Microbiology, Institut Clinic Infeccions i Immunologia, Hospital Clinic, C Villarroel 170, 08036 Barcelona, Spain
    J Antimicrob Chemother 51:1109-17. 2003
    ..Recently, mobile elements have also been described, carrying the qnr gene, which confers resistance to quinolones...
  70. ncbi Molecular characterization of genes encoding the quinolone resistance determining regions of Malaysian Streptococcus pneumoniae strains
    N Kumari
    Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur 50603, Malaysia
    Indian J Med Microbiol 26:148-50. 2008
    ..pneumoniae isolates in Malaysia. However, further experimental work is required to confirm the involvement of this mutation in the development of fluoroquinolone resistance in Malaysia...
  71. ncbi High-level fluoroquinolone resistance in a clinical Streptoccoccus pyogenes isolate in Germany
    R R Reinert
    Institute of Medical Microbiology, National Reference Centre for Streptococci, University Hospital, Aachen, Germany
    Clin Microbiol Infect 10:659-62. 2004
    ..To our knowledge, this is the first report from a European country of a clinical isolate of S. pyogenes with high-level fluoroquinolone resistance...
  72. ncbi In vitro antibacterial activity of fluoroquinolones against Porphyromonas gingivalis strains
    Sigrun Eick
    Institute of Medical Microbiology, University Hospital, Semmelweisstrasse 4, D 07740 Jena, Germany
    J Antimicrob Chemother 54:553-6. 2004
    ..The objective of the study was to evaluate the in vitro activity of ciprofloxacin, gatifloxacin and moxifloxacin against 16 Porphyromonas gingivalis strains...
  73. ncbi In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus
    Gregory T Robertson
    Cumbre Pharmaceuticals Inc, 1502 Viceroy Drive, Dallas, TX 75235 2304, USA
    Antimicrob Agents Chemother 52:2313-23. 2008
    ..exhibited rifampin-like 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...
  74. ncbi Single-nucleotide polymorphism mutation spectra and resistance to quinolones in Salmonella enterica serovar Enteritidis with a mutator phenotype
    Dan D Levy
    Division of Molecular Biology, Center for Food Safety and Nutrition, U.S. Food and Drug Administration, HFS-025, 8301 Muirkirk Road, Laurel, MD 20708, USA
    Antimicrob Agents Chemother 48:2355-63. 2004
    ....
  75. ncbi Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae from Asian countries: ANSORP study
    Won Sup Oh
    Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
    Microb Drug Resist 10:37-42. 2004
    ..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...
  76. ncbi In vitro activity of sitafloxacin against clinical strains of Streptococcus pneumoniae with defined amino acid substitutions in QRDRs of gyrase A and topoisomerase IV
    Masato Touyama
    Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan
    J Antimicrob Chemother 58:1279-82. 2006
    ..016-0.5 mg/L. CONCLUSIONS: These findings warrant further studies to evaluate the usefulness of sitafloxacin in the treatment of levofloxacin-resistant S. pneumoniae infection...
  77. ncbi In vitro development of resistance to DX-619 and other quinolones in enterococci
    Paul A Wickman
    Department of Medical Microbiology and Immunology, Center for Research in Anti Infectives and Biotechnology, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
    J Antimicrob Chemother 58:1268-73. 2006
    ..To investigate the molecular events involved in the development of quinolone resistance in enterococci...
  78. ncbi Mutations in the gyrA and parC genes and in vitro activities of fluoroquinolones in 91 clinical isolates of Neisseria gonorrhoeae in Japan
    Katsumi Shigemura
    Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    Sex Transm Dis 31:180-4. 2004
    ..CONCLUSION: Some mutations in QRDR had a significant relationship to the fluoroquinolone resistance of N. gonorrhoeae clinical isolates from Japan...
  79. ncbi Role of topoisomerase mutations and efflux in fluoroquinolone resistance of Bacteroides fragilis clinical isolates and laboratory mutants
    Vito Ricci
    Antimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
    Antimicrob Agents Chemother 48:1344-6. 2004
    ....
  80. ncbi Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies
    A A Vickers
    Antimicrobial Research Centre and Research Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
    J Antimicrob Chemother 60:269-73. 2007
    ..to these agents in Staphylococcus aureus and determined the effect of simultaneous topoisomerase IV and DNA gyrase mutations on the biological fitness of the organism...
  81. ncbi The first steps towards fluoroquinolone resistance in Hungarian pneumococci
    O Dobay
    University of Edinburgh, Scotland, UK
    J Chemother 18:624-7. 2006
    ..These two findings, coupled with the increasing consumption figures of fluoroquinolones, suggest that pneumococcal resistance looks poised to develop in Hungary...
  82. ncbi High occurrence of simultaneous mutations in target enzymes and MtrRCDE efflux system in quinolone-resistant Neisseria gonorrhoeae
    Beti Ernawati Dewi
    Department of Infection Biology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan
    Sex Transm Dis 31:353-9. 2004
    ..CONCLUSION: This study reports simultaneous mutations in fluoroquinolone target enzymes and the MtrRCDE efflux system as a fluoroquinolone-resistant mechanism in N. gonorrhoeae...
  83. ncbi Activities of different fluoroquinolones against Bacillus anthracis mutants selected in vitro and harboring topoisomerase mutations
    Patrick Grohs
    Service de Microbiologie, , Paris, France
    Antimicrob Agents Chemother 48:3024-7. 2004
    ..Among the fluoroquinolones tested, garenoxacin showed the best activity...
  84. ncbi Relative potential for selection of quinolone-resistance-determining-region mutations in Streptococcus pneumoniae by gemifloxacin, gatifloxacin and moxifloxacin
    J C S De Azavedo
    Toronto Centre for Antimicrobial Research and Evaluation ToCARE, Dept of Microbiology, Mount Sinai Hospital, Canada
    J Chemother 18:373-8. 2006
    ..and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in ..
  85. ncbi Antimicrobial resistance of Neisseria gonorrhoeae in Japan, 1993-2002: continuous increasing of ciprofloxacin-resistant isolates
    Masatoshi Tanaka
    Department of Urology, Fukuoka University School of Medicine, 7 45 1 Nanakuma, Jonan ku, Fukuoka 814 0180, Fukuoka, Japan
    Int J Antimicrob Agents 24:S15-22. 2004
    ..3%) contained five amino acid substitutions within the GyrA and ParC proteins, 76 (87.4%) contained three or four amino acid substitutions and 9 (10.3%) contained one or two amino acid substitutions...
  86. ncbi Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumoniae
    Ryo Okumura
    Biological Research Laboratories IV, Daiichi Sankyo Co, Ltd, 1 16 13 Kitakasai, Edogawa ku, Tokyo 134 8630, Japan
    J Antimicrob Chemother 62:98-104. 2008
    ..We investigated the relationship between the target preferences of these 3-aminopyrrolidyl quinolones, in vitro potencies and emergence of quinolone-resistant mutants in Streptococcus pneumoniae, compared with other quinolones...
  87. ncbi 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
    M Alkorta
    Servicio de Microbiologia, Hospital Donostia, Po del Doctor Beguiristain s n, 20014 San Sebastian, Spain
    Int J Antimicrob Agents 25:163-7. 2005
    ....
  88. ncbi Fluoroquinolone resistance and gyrA and parC mutations of Escherichia coli isolated from chicken
    Young Ju Lee
    College of Veterinary Medicine, Kyungpook National University, Daegu 702 701, Republic of Korea
    J Microbiol 43:391-7. 2005
    ....
  89. ncbi Uncommon occurrence of fluoroquinolone resistance-associated alterations in GyrA and ParC in clinical strains of Chlamydia trachomatis
    Shigeaki Yokoi
    Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagaido, Gifu, 501-1194, Japan
    J Infect Chemother 10:262-7. 2004
    ..The present study suggests that fluoroquinolone resistance-associated alterations in GyrA and ParC may be uncommon in clinical strains of C. trachomatis...
  90. ncbi Intrinsic reduced susceptibility of serotype 6 Streptococcus pyogenes to fluoroquinolone antibiotics
    Rachel C Orscheln
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Infect Dis 191:1272-9. 2005
    ..Fluoroquinolone resistance is common in Staphylococcus aureus, is increasing in Streptococcus pneumoniae, and is reported in Streptococcus pyogenes...
  91. ncbi Fluoroquinolone-resistant mutants of Burkholderia cepacia
    C F Pope
    Centre for Medical Microbiology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom
    Antimicrob Agents Chemother 52:1201-3. 2008
    ..Growth rate, biofilm formation, and survival in water and during drying were not impaired in strains containing single gyrA mutations. Double mutants were impaired only in growth rate (0.85, relative to the susceptible parent)...
  92. ncbi In vitro assessment of the further potential for development of fluoroquinolone resistance in Neisseria meningitidis
    Tiffany R Shultz
    Department of Microbiology, South Eastern Area Laboratory Service, The Prince of Wales Hospital, Sydney 2031, Australia
    Antimicrob Agents Chemother 49:1753-60. 2005
    ..This suggests that quinolone resistance in meningococci may arise in the same manner and reach similar levels in vivo to those seen in quinolone-resistant Neisseria gonorrhoeae...
  93. ncbi Alterations in the GyrA and GyrB subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa
    Jeom Kyu Lee
    Department of Bacteriology, National Institute of Health, Korea Center for Disease Control and Prevention, 5 Nokbeon-dong, Eunpyeong-gu, Seoul, Republic of Korea
    Int J Antimicrob Agents 25:290-5. 2005
    ..There was a correlation between the ciprofloxacin MIC and the number of resistance-associated alterations in GyrA, GyrB, ParC and ParE of P. aeruginosa isolates...
  94. ncbi Fluoroquinolone-resistant Streptococcus agalactiae: epidemiology and mechanism of resistance
    Wehbeh Wehbeh
    Infectious Disease Section, Department of Medicine and Lang Research Center, New York Hospital Queens, 56 45 Main Street, Flushing, NY 11355, USA
    Antimicrob Agents Chemother 49:2495-7. 2005
    ..agalactiae bacteria were isolated from the same patient...
  95. ncbi Characterization of fluoroquinolone and carbapenem susceptibilities in clinical isolates of levofloxacin-resistant Pseudomonas aeruginosa
    Hideaki Muramatsu
    Division of Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan
    Chemotherapy 51:70-5. 2005
    ..Our results suggest that susceptibilities to fluoroquinolones as well as carbapenems should be monitored during a prolonged course of antibiotic therapy against P. aeruginosa infection...
  96. ncbi Accumulation of mutations in both gyrB and parE genes is associated with high-level resistance to novobiocin in Staphylococcus aureus
    Mika Fujimoto-Nakamura
    Pharmacology and Microbiology Research Laboratories, Dainippon Pharmaceutical Co, Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan
    Antimicrob Agents Chemother 49:3810-5. 2005
    ..These findings demonstrate that DNA gyrase is the primary target and that topoisomerase IV is the secondary target for novobiocin and that the accumulation ..
  97. ncbi In vitro antibacterial activities of new fluoroquinolones against clinical isolates of haemophilus influenzae with ciprofloxacin-resistance-associated alterations in GyrA and ParC
    Satoshi Yoshizumi
    Department of Microbiology, Toho University School of Medicine, Tokyo, Japan
    Chemotherapy 50:265-75. 2004
    ..The in vitro antimicrobial activities of new fluoroquinolones were tested against quinolone-resistant Haemophilus influenzae of clinical isolates...
  98. ncbi Molecular characterization of clinical Streptococcus pneumoniae isolates with reduced susceptibility to fluoroquinolones emerging in Italy
    Maria Pia Montanari
    Department of Microbiology and Biomedical Sciences, Polytechnic University of Marche Medical School, 60131 Ancona, Italy
    Microb Drug Resist 10:209-17. 2004
    ..changes were more frequent in topoisomerase IV (parC mutations in 14 isolates and parE mutations in 13) than in DNA gyrase subunits (gyrA mutations in 7 isolates and no gyrB mutations observed)...
  99. ncbi [Genetical conditioning of fluoroquinolone resistance mechanisms of clinical enterococcus faecalis strains. II. The mutations present in the qrdrs of gyrA, gyrB, parC and parE genes]
    Katarzyna Piekarska
    Zakład Bakteriologii Państwowego Zakładu Higieny w Warszawie
    Med Dosw Mikrobiol 59:329-41. 2007
    ..The amino acid substitutions of GyrA, GyrB and ParC were observed. The results indicate that mutations present among clinical E. faecalis strains associated with high level resistance to fluoroquinolons...
  100. ncbi Topoisomerase mutations and efflux are associated with fluoroquinolone resistance in Enterococcus faecalis
    Yoshihiro Oyamada
    Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd, Enoki 33-94, Osaka 564-0053, Japan
    J Med Microbiol 55:1395-401. 2006
    ..faecalis are DNA gyrase and topoisomerase IV, respectively...
  101. ncbi Bactericidal activity and target preference of a piperazinyl-cross-linked ciprofloxacin dimer with Staphylococcus aureus and Escherichia coli
    Xilin Zhao
    Public Health Research Institute, 225 Warren Street, Newark, NJ 07103, USA
    J Antimicrob Chemother 58:1283-6. 2006
    ..coli, representative gram-positive and gram-negative bacteria. In both cases the preferred target was DNA gyrase. The switch in target preference may be responsible for the greater lethality of the dimer seen with S. aureus.

Research Grants97

  1. Plasmid-Mediated Quinolone Resistance
    George A Jacoby; Fiscal Year: 2010
    ..Quinolone resistance has traditionally been understood to arise either by mutations that alter DNA gyrase and topoisomerase IV, enzymes that are the targets for quinolone action or by mutations that increase expression ..
  2. Plasmid-Mediated Quinolone Resistance
    David Hooper; Fiscal Year: 2009
    ..Quinolone resistance has traditionally been understood to arise either by mutations that alter DNA gyrase and topoisomerase IV, enzymes that are the targets for quinolone action or by mutations that increase expression ..
  3. QUINOLONE RESISTANCE MECHANISMS IN STAPHYLOCOCCUS AUREUS
    David Hooper; Fiscal Year: 2002
    ..is that topoisomerase IV seems to be the main fluoroquinolone target in the gram positive bacteria rather than DNA gyrase, and this makes it possible to investigate the function and regulation of topoisomerases in ways not possible in ..
  4. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth N Kreuzer; Fiscal Year: 2010
    ..The quinolone antibiotics, which target bacterial DNA gyrase, stabilize a reaction intermediate in which the enzyme is covalently attached to a broken DNA molecule via ..
  5. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth N Kreuzer; Fiscal Year: 2010
    ..The quinolone antibiotics, which target bacterial DNA gyrase, stabilize a reaction intermediate in which the enzyme is covalently attached to a broken DNA molecule via ..
  6. PATHOBIOCHEMISTRY OF CHLAMYDIA TRACHOMONAS HUMAN SEXUALLY TRANSMITTED DISEASES
    BIBHUTI SINGH; Fiscal Year: 2001
    E. coli microcin B17 (MccB17) is a posttranslationally modified peptide antibiotic that inhibits bacterial DNA gyrase. It contains four oxazole and four thiazole rings and is representative of a broad class of pharmaceutically important ..
  7. Modular Enzymatic Assembly Lines for Antibiotics
    Christopher Walsh; Fiscal Year: 2007
    ..that generate the 5-methylpyrrolycarboxyl moiety that interacts with the ATP site of the GyrB subunit of DNA gyrase. It also focuses on companion 2 His/Asp- Fe (11)enzymes proposed to be cyclopropanation catalyst (coronamic acid ..
  8. ROLE OF TOPOISOMERASES IN DNA REPLICATION
    KENNETH MARIANS; Fiscal Year: 1990
    ..binding protein, the dnaB, dnaC and dnaG (primase) proteins, proteins i, n, n' (replication factor Y), and n", DNA gyrase and topoisomerase I...
  9. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN P HIGGINS; Fiscal Year: 2010
    ..This aim includes a new component involving DNA gyrase biochemistry and genetic methods that evolved from the E. coli/Salmonella species comparison...
  10. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN HIGGINS; Fiscal Year: 2009
    ..This aim includes a new component involving DNA gyrase biochemistry and genetic methods that evolved from the E. coli/Salmonella species comparison...
  11. MECHANISMS OF TOPOISOMERASE POISONS
    Hiroshi Hiasa; Fiscal Year: 2002
    ..in eukaryotes these enzymes are the cellular targets of potent anticancer drugs, whereas in prokaryotes both DNA Gyrase and topoisomerase IV (Topo IV) are targets of the most potent broad-spectrum antibacterial agents (e.q...
  12. Lethal action of fluoroquinolones with non-growing Mycobacterium tuberculosis
    Karl Drlica; Fiscal Year: 2007
    ..tuberculosis. M. tuberculosis DNA gyrase, the molecular target of quinolones, will be purified and used to study biochemical interactions of quinolones ..
  13. Fluoroquinolone Resistance in M. Tuberculosis
    Timothy Sterling; Fiscal Year: 2007
    ..Fluoroquinolone resistance in M. tuberculosis can occur due to a single base-pair mutation in DNA gyrase. However, genetic mutations have not been identified in all fluoroquinolone-resistant M...
  14. Lethal action of fluoroquinolones with non-growing Mycobacterium tuberculosis
    KARL A DRLICA; Fiscal Year: 2010
    ..tuberculosis. M. tuberculosis DNA gyrase, the molecular target of quinolones, will be purified and used to study biochemical interactions of quinolones ..
  15. Lethal action of fluoroquinolones with non-growing Mycobacterium tuberculosis
    Karl Drlica; Fiscal Year: 2009
    ..tuberculosis. M. tuberculosis DNA gyrase, the molecular target of quinolones, will be purified and used to study biochemical interactions of quinolones ..
  16. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN HIGGINS; Fiscal Year: 2001
    ..Two essential genes in bacteria, DNA gyrase and Topoisomerase IV, have both turned up in this screen. Other genes will be mapped and characterized...
  17. Quinolone Action During Mycobacterial Growth Arrest
    Karl Drlica; Fiscal Year: 2006
    ..b>DNA gyrase mutants have been identified that enhance this minor pathway...
  18. Mechanism and Spread of Qnr-Mediated Resistance
    David Hooper; Fiscal Year: 2007
    ..We discovered a plasmid-encoded protein termed Qnr that protects DNA gyrase from quinolone inhibition...
  19. PLASMID MEDIATED QUINOLONE RESISTANCE
    George Jacoby; Fiscal Year: 2001
    ..but the predicted protein (termed Qnr) has similarity to the microcin B17 immunity protein which protects DNA gyrase from microcin inhibition...
  20. ROLE OF TOPOISOMERASES IN DNA METABOLISM
    KENNETH MARIANS; Fiscal Year: 1993
    ..or bidirectional replication, we will study the influence of the three Escherichia coli topoisomerases, DNA gyrase, topoisomerase I (Topo I), and topoisomerase III (Topo III) on the termination and segregation stages of DNA ..
  21. Plasmid-Mediated Quinolone Resistance
    George Jacoby; Fiscal Year: 2007
    ..We discovered a plasmid-encoded protein termed Qnr that protects DNA gyrase from quinolone inhibition...
  22. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2002
    ..First, resistance arises stepwise from mutations in two independent targets, DNA gyrase and DNA topoisomerase IV...
  23. ENZYMATIC REACTION MECHANISMS
    Christopher Walsh; Fiscal Year: 2003
    ..coli DNA gyrase, in which 14 residues (six gly, four ser, four cys) have been posttranslationally modified to four thiazole and ..
  24. CONTROL OF DNA TOPOLOGY
    Yuk Ching Tse Dinh; Fiscal Year: 1999
    ..Eukaryotic topoisomerases and DNA gyrase are known targets for anti-cancer and anti-bacterial drugs...
  25. CONTROL OF DNA TOPOLOGY
    Yuk Ching Tse Dinh; Fiscal Year: 2003
    ..DNA religation would lead to cell killing in a mechanism similar to those of many drugs targeting bacterial DNA gyrase and human topoisomerases...
  26. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2007
    ..abstract_text> ..
  27. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2006
    ..abstract_text> ..
  28. Principles of Protein Mimicry of DNA
    MICHAEL D BRENOWITZ; Fiscal Year: 2010
    ..to the biological role of MfpA is suggested by its ability to confer resistance to fluoro- quinolones by binding DNA gyrase thereby inhibiting its function...
  29. Principles of Protein Mimicry of DNA
    Michael Brenowitz; Fiscal Year: 2009
    ..to the biological role of MfpA is suggested by its ability to confer resistance to fluoro- quinolones by binding DNA gyrase thereby inhibiting its function...
  30. BIOCHEMICAL STUDIES OF PHAGE MU
    NORMAN HIGGINS; Fiscal Year: 1990
    ..stimulates lytic transcription and decreases repressor transcription; thus, the virus is sensitive to DNA gyrase activity of the host. A binding site for a type II DNA binding protein of E...