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. pmc The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks
    Andrew D Bates
    Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK
    Nucleic Acids Res 39:6327-39. 2011
  2. ncbi DNA topoisomerases: harnessing and constraining energy to govern chromosome topology
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biology, University of California Berkeley, Berkeley, CA, USA
    Q Rev Biophys 41:41-101. 2008
  3. pmc Exploiting bacterial DNA gyrase as a drug target: current state and perspectives
    Frédéric Collin
    Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK
    Appl Microbiol Biotechnol 92:479-97. 2011
  4. ncbi Origin and evolution of DNA topoisomerases
    Patrick Forterre
    Institut de Genetique et Microbiologie, UMR8621, Universite Paris Sud 11, Bat 400 409, 91405 Orsay Cedex, France
    Biochimie 89:427-46. 2007
  5. ncbi Type IIA topoisomerase inhibition by a new class of antibacterial agents
    Benjamin D Bax
    Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK
    Nature 466:935-40. 2010
  6. 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
  7. 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
  8. pmc Interplay in the selection of fluoroquinolone resistance and bacterial fitness
    Linda L Marcusson
    Microbiology Programme, Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden
    PLoS Pathog 5:e1000541. 2009
  9. ncbi ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase
    Yong Jiang
    Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093 0322, USA
    Mol Microbiol 44:971-9. 2002
  10. pmc 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

Detail Information

Publications356 found, 100 shown here

  1. pmc The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks
    Andrew D Bates
    Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK
    Nucleic Acids Res 39:6327-39. 2011
    ..All type II topos hydrolyse ATP during their reactions; however, only DNA gyrase is able to harness the free energy of hydrolysis to drive DNA supercoiling, an energetically unfavourable ..
  2. ncbi DNA topoisomerases: harnessing and constraining energy to govern chromosome topology
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biology, University of California Berkeley, Berkeley, CA, USA
    Q Rev Biophys 41:41-101. 2008
    ....
  3. pmc Exploiting bacterial DNA gyrase as a drug target: current state and perspectives
    Frédéric Collin
    Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK
    Appl Microbiol Biotechnol 92:479-97. 2011
    b>DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials...
  4. ncbi Origin and evolution of DNA topoisomerases
    Patrick Forterre
    Institut de Genetique et Microbiologie, UMR8621, Universite Paris Sud 11, Bat 400 409, 91405 Orsay Cedex, France
    Biochimie 89:427-46. 2007
    ....
  5. ncbi Type IIA topoisomerase inhibition by a new class of antibacterial agents
    Benjamin D Bax
    Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK
    Nature 466:935-40. 2010
    ..structure of a potent, new class, broad-spectrum antibacterial agent in complex with Staphylococcus aureus DNA gyrase and DNA, showing a new mode of inhibition that circumvents fluoroquinolone resistance in this clinically ..
  6. 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
    ....
  7. 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...
  8. pmc Interplay in the selection of fluoroquinolone resistance and bacterial fitness
    Linda L Marcusson
    Microbiology Programme, Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden
    PLoS Pathog 5:e1000541. 2009
    Fluoroquinolones are antibacterial drugs that inhibit DNA Gyrase and Topoisomerase IV. These essential enzymes facilitate chromosome replication and RNA transcription by regulating chromosome supercoiling...
  9. ncbi ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase
    Yong Jiang
    Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093 0322, USA
    Mol Microbiol 44:971-9. 2002
    ..Adding ParD before or after the addition of ParE prevented the formation of this cleavable complex. These results demonstrate that the target of ParE toxin activity in vitro is E. coli gyrase...
  10. pmc 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...
  11. ncbi ATP binding controls distinct structural transitions of Escherichia coli DNA gyrase in complex with DNA
    Aakash Basu
    Department of Applied Physics, Stanford University, Stanford, California, USA
    Nat Struct Mol Biol 19:538-46, S1. 2012
    b>DNA gyrase is a molecular motor that harnesses the free energy of ATP hydrolysis to introduce negative supercoils into DNA. A critical step in this reaction is the formation of a chiral DNA wrap...
  12. pmc Rates of gyrase supercoiling and transcription elongation control supercoil density in a bacterial chromosome
    Nikolay Rovinskiy
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
    PLoS Genet 8:e1002845. 2012
    ..The observed link between RNA polymerase elongation speed and gyrase turnover suggests that bacteria with fast growth rates may generate higher supercoil densities than slow growing species...
  13. pmc Mechanisms for defining supercoiling set point of DNA gyrase orthologs: II. The shape of the GyrA subunit C-terminal domain (CTD) is not a sole determinant for controlling supercoiling efficiency
    Elsa M Tretter
    Division of Biochemistry, Biophysics, and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    J Biol Chem 287:18645-54. 2012
    ..Our observations demonstrate that gyrase has been modified in multiple ways throughout evolution to fine-tune its specific catalytic properties...
  14. ncbi Topological insulators inhibit diffusion of transcription-induced positive supercoils in the chromosome of Escherichia coli
    Laurent Moulin
    Centre de Génétique Moléculaire du CNRS, Bat 26, 1 Avenue de la Terrasse, F 91198 Gif sur Yvette, France and Centre de Biophysique Moléculaire du CNRS, Avenue Ch Sadron, F 45071 Orléans, France
    Mol Microbiol 55:601-10. 2005
    ..e. behave as topological insulators. All the elements tested correspond to DNA gyrase catalytic targets...
  15. pmc 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...
  16. pmc A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system
    Fernanda Maruri
    Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    J Antimicrob Chemother 67:819-31. 2012
    ..A review of mutations in DNA gyrase, the fluoroquinolone target, is needed to improve the molecular detection of resistance...
  17. pmc Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pylori
    Jacques Tankovic
    Laboratoire de Bacteriologie, Centre Hospitalo Universitaire Saint Antoine, Assistance Publique Hopitaux de Paris, Universite Paris VI, Paris, France
    Antimicrob Agents Chemother 47:3942-4. 2003
    ..Clinafloxacin and garenoxacin were the most active fluoroquinolones against these mutants. Occurrence of a second gyrA mutation was associated with high MICs of all fluoroquinolones tested...
  18. pmc New insights into fluoroquinolone resistance in Mycobacterium tuberculosis: functional genetic analysis of gyrA and gyrB mutations
    Seidu Malik
    Laboratory Branch, Division of Tuberculosis Elimination, National Center for HIV AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
    PLoS ONE 7:e39754. 2012
    ..The results from this study provide support for the inclusion of the QRDR of gyrB in molecular assays used to detect fluoroquinolone resistance in M. tuberculosis...
  19. pmc 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
    Deborah J Eaves
    Antimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
    Antimicrob Agents Chemother 48:4012-5. 2004
    ..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...
  20. ncbi Distribution of fluoroquinolone MICs in Helicobacter pylori strains from Korean patients
    Jung Mogg Kim
    Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea
    J Antimicrob Chemother 56:965-7. 2005
    ..The aim of this study was to assess the prevalence rate of primary fluoroquinolone resistance in Helicobacter pylori isolates from Korean patients over the past 16 years...
  21. 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...
  22. ncbi Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibiotics
    Silke Alt
    Pharmaceutical Biology, Pharmaceutical Institute, University of Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    J Antimicrob Chemother 66:2061-9. 2011
    Aminocoumarin antibiotics are potent inhibitors of bacterial DNA gyrase. We investigated the inhibitory and antibacterial activity of naturally occurring aminocoumarin antibiotics and six structural analogues (novclobiocins) against DNA ..
  23. pmc Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A nonconserved acidic C-terminal tail modulates Escherichia coli gyrase activity
    Elsa M Tretter
    Division of Biochemistry, Biophysics, and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    J Biol Chem 287:18636-44. 2012
    ..coli GyrA tail regulates DNA wrapping by the CTD to increase the coupling efficiency between ATP turnover and supercoiling, demonstrating that CTD functions can be fine-tuned to control gyrase activity in a highly sophisticated manner...
  24. pmc Housekeeping gene sequencing and multilocus variable-number tandem-repeat analysis to identify subpopulations within Pseudomonas syringae pv. maculicola and Pseudomonas syringae pv. tomato that correlate with host specificity
    S Gironde
    INRA, UMR 1345 Institut de Recherche en Horticulture et Semences IRHS, INRA, Agrocampus Ouest, Universite d Angers, Beaucouze, France
    Appl Environ Microbiol 78:3266-79. 2012
    ..tomato appear multiclonal, as they did not diverge from a single common ancestral group within the ancestral P. syringae genomospecies 3, and suggests that pathovar specificity within P. syringae may be due to independent genetic events...
  25. pmc Application of a novel microtitre plate-based assay for the discovery of new inhibitors of DNA gyrase and DNA topoisomerase VI
    James A Taylor
    Department of Biological Chemistry, John Innes Centre, Colney Lane, Norwich, United Kingdom
    PLoS ONE 8:e58010. 2013
    ..A library of 960 compounds was screened against Escherichia coli DNA gyrase and archaeal Methanosarcina mazei DNA topoisomerase VI...
  26. ncbi Comparative phylogenies of Burkholderia, Ralstonia, Comamonas, Brevundimonas and related organisms derived from rpoB, gyrB and rrs gene sequences
    Lineda Ait Tayeb
    Unit Biodiversity of Emerging Bacterial Pathogens, Institut Pasteur Paris, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
    Res Microbiol 159:169-77. 2008
    ..Nevertheless, intraspecific sequence diversity will need to be determined to fully establish the value of these genes for strain identification...
  27. pmc Cellulose degradation by micromonosporas recovered from freshwater lakes and classification of these actinomycetes by DNA gyrase B gene sequencing
    Alexandre B de Menezes
    School of Biological Sciences, Biosciences Building, University of Liverpool, Crown Street, Liverpool, Merseyside L69 7ZB, United Kingdom
    Appl Environ Microbiol 74:7080-4. 2008
    ..chalcea...
  28. pmc DNA gyrase inhibition assays are necessary to demonstrate fluoroquinolone resistance secondary to gyrB mutations in Mycobacterium tuberculosis
    Alix Pantel
    UPMC Universite Paris 06, ER5, EA 1541, Laboratoire de Bacteriologie Hygiene, F 75005 Paris, France
    Antimicrob Agents Chemother 55:4524-9. 2011
    The main mechanism of fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis is mutation in DNA gyrase (GyrA(2)GyrB(2)), especially in gyrA...
  29. pmc Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistance
    Hyun Kim
    Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001 0020, Japan
    Antimicrob Agents Chemother 55:3661-7. 2011
    ..have generally been found within the quinolone resistance-determining regions (QRDRs) in the A subunit of DNA gyrase (GyrA) rather than the B subunit of DNA gyrase (GyrB)...
  30. pmc Rapid detection of fluoroquinolone-resistant and heteroresistant Mycobacterium tuberculosis by use of sloppy molecular beacons and dual melting-temperature codes in a real-time PCR assay
    Soumitesh Chakravorty
    Division of Infectious Disease, Department of Medicine and the Ruy V Lourenço Center for the Study of Emerging and Reemerging Pathogens, New Jersey Medical School, Newark, NJ 07103, USA
    J Clin Microbiol 49:932-40. 2011
    ..This SMB T(m) shift assay will be a valuable molecular tool to rapidly detect FQ resistance and to detect the emergence of FQ heteroresistance in clinical samples from tuberculosis patients...
  31. 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...
  32. pmc 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...
  33. pmc 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...
  34. pmc 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...
  35. ncbi Prevalence of primary fluoroquinolone resistance among clinical isolates of Helicobacter pylori at a University Hospital in Southern Taiwan
    Kuei Hsiang Hung
    Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    Helicobacter 14:61-5. 2009
    ..pylori to fluoroquinolones in Taiwan has not yet been reported. In this study, we aimed to investigate the susceptibility to antibiotics commonly used in eradication schedules and fluoroquinolones in H. pylori...
  36. pmc 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...
  37. pmc Quinolone resistance in Escherichia coli from Accra, Ghana
    Sreela S Namboodiri
    Department of Biology, Haverford College, Haverford, PA 19041, USA
    BMC Microbiol 11:44. 2011
    ..We sought to determine the prevalence of resistance to broad-spectrum antimicrobials with particular focus on the quinolones, which have recently been introduced in parts of Africa, including Ghana...
  38. pmc 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 ..
  39. ncbi Reduction of the fitness burden of quinolone resistance in Pseudomonas aeruginosa
    Elisabeth Kugelberg
    Swedish Institute for Infectious Disease Control, Department of Bacteriology, S 171 82 Solna, Sweden
    J Antimicrob Chemother 55:22-30. 2005
    ..opportunistic pathogen Pseudomonas aeruginosa is commonly caused by mutations that alter the target molecules DNA gyrase/topoisomerase IV, or cause activation of various efflux systems...
  40. pmc 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...
  41. ncbi First functional characterization of a singly expressed bacterial type II topoisomerase: the enzyme from Mycobacterium tuberculosis
    Alexandra Aubry
    Laboratoire de Bacteriologie, Faculté de Médecine Pitié Salpêtrière, EA1541, Universite Paris 6, France
    Biochem Biophys Res Commun 348:158-65. 2006
    ..encodes a single type II topoisomerase contrary to common bacteria harboring two type II topoisomerases (DNA gyrase and topoisomerase IV). Functions of the M...
  42. pmc gyrA mutations associated with fluoroquinolone resistance in eight species of Enterobacteriaceae
    L M Weigel
    Hospital Infections Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
    Antimicrob Agents Chemother 42:2661-7. 1998
    ..Two mechanisms of FQ-R have been identified in gram-negative organisms: mutations in DNA gyrase and reduced intracellular drug accumulation...
  43. pmc 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...
  44. pmc 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...
  45. pmc Evolutionary history of Salmonella typhi
    Philippe Roumagnac
    Max Planck Institut für Infektionsbiologie, Department of Molecular Biology, Chariteplatz 1, 10117 Berlin, Germany
    Science 314:1301-4. 2006
    ..Neutral evolution in Typhi appears to reflect the asymptomatic carrier state, and adaptive evolution depends on the rapid transmission of phenotypic changes through acute infections...
  46. pmc 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...
  47. ncbi Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in India
    R Gaind
    Department of Microbiology, Safdarjung Hospital and Assoc VMMC, New Delhi, India
    J Antimicrob Chemother 58:1139-44. 2006
    ..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...
  48. pmc 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...
  49. 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)...
  50. pmc DNA-induced narrowing of the gyrase N-gate coordinates T-segment capture and strand passage
    Airat Gubaev
    Institute for Physical Chemistry, University of Muenster, Corrensstrasse 30, D 48149 Muenster, Germany
    Proc Natl Acad Sci U S A 108:14085-90. 2011
    b>DNA gyrase introduces negative supercoils into DNA in an ATP-dependent reaction. DNA supercoiling is catalyzed by a strand-passage mechanism, in which a T-segment of DNA is passed through the gap in a transiently cleaved G-segment...
  51. ncbi gyrB as a phylogenetic discriminator for members of the Bacillus anthracis-cereus-thuringiensis group
    Myron T La Duc
    Biotechnology and Planetary Protection Group, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA
    J Microbiol Methods 56:383-94. 2004
    ..The gyrB gene proved more highly differential than 16S, while, at the same time, as analytical as costly and laborious DNA:DNA hybridization techniques in differentiating species within the B. cereus group...
  52. ncbi Drug-sensing hydrogels for the inducible release of biopharmaceuticals
    Martin Ehrbar
    Department of Cranio Maxillofacial Surgery, University Hospital Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland
    Nat Mater 7:800-4. 2008
    ..Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient...
  53. ncbi gyrA and gyrB gene mutation in ciprofloxacin-resistant Mycobacterium massiliense clinical isolates from Southern Brazil
    Fernanda Monego
    Pós graduação em Biologia Celular e Molecular, Universidade Federal do Parana, Curitiba, Parana, Brazil
    Microb Drug Resist 18:1-6. 2012
    ..No gyrB mutation was observed in all tested M. massiliense isolates. In conclusion, our results have shown that mutations of gyrA codon 90 are frequent and may constitute an important mechanism of resistance to FQ in M. massiliense...
  54. pmc DNA gyrase and topoisomerase IV mutations associated with fluoroquinolone resistance in Proteus mirabilis
    L M Weigel
    Division of Healthcare Quality Promotion, Anti infectives Section G 08, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333, USA
    Antimicrob Agents Chemother 46:2582-7. 2002
    ..Unlike any other bacterial species analyzed to date, mutation of gyrB appears to be a frequent event in the acquisition of fluoroquinolone resistance among clinical isolates of P. mirabilis...
  55. ncbi GyrB sequence analysis and MALDI-TOF MS as identification tools for plant pathogenic Clavibacter
    Joanna Zaluga
    Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, K L Ledeganckstraat 35, B 9000 Ghent, Belgium
    Syst Appl Microbiol 34:400-7. 2011
    ..Our study suggests that proteomic analysis using MALDI-TOF MS and gyrB sequence are powerful diagnostic tools for the accurate identification of Clavibacter plant pathogens...
  56. pmc Cloning and characterization of the parC and parE genes of Streptococcus pneumoniae encoding DNA topoisomerase IV: role in fluoroquinolone resistance
    X S Pan
    Molecular Genetics Group, Department of Cellular and Molecular Sciences, St George s Hospital Medical School, University of London, United Kingdom
    J Bacteriol 178:4060-9. 1996
    ..These results suggest that DNA topoisomerase IV is an important target for fluoroquinolones in S. pneumoniae and establish this organism as a useful gram-positive system for resistance studies...
  57. pmc Functional characterisation of mycobacterial DNA gyrase: an efficient decatenase
    U H Manjunatha
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India
    Nucleic Acids Res 30:2144-53. 2002
    A rapid single step immunoaffinity purification procedure is described for Mycobacterium smegmatis DNA gyrase. The mycobacterial enzyme is a 340 kDa heterotetrameric protein comprising two subunits each of GyrA and GyrB, exhibiting subtle ..
  58. ncbi Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitors
    Matjaz Brvar
    National Institute of Chemistry, Laboratory for Biocomputing and Bioinformatics, 1001 Ljubljana, Slovenia
    J Med Chem 55:6413-26. 2012
    Bacterial DNA gyrase is a well-established and validated target for the development of novel antibacterials...
  59. pmc Mechanisms of fluoroquinolone resistance in Escherichia coli isolates from food-producing animals
    Maria Karczmarczyk
    UCD Centre for Food Safety and Centre for Food borne Zoonomics, UCD Veterinary Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland
    Appl Environ Microbiol 77:7113-20. 2011
    ..This study identified multiple mechanisms that likely contribute to resistance to quinolone-based drugs in the field isolates studied...
  60. pmc The key DNA-binding residues in the C-terminal domain of Mycobacterium tuberculosis DNA gyrase A subunit (GyrA)
    You Yi Huang
    State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    Nucleic Acids Res 34:5650-9. 2006
    As only the type II topoisomerase is capable of introducing negative supercoiling, DNA gyrase is involved in crucial cellular processes...
  61. pmc Mechanisms accounting for fluoroquinolone resistance in Escherichia coli clinical isolates
    Sonia K Morgan-Linnell
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030 3411, USA
    Antimicrob Agents Chemother 53:235-41. 2009
    ..Thus, additional, unknown fluoroquinolone resistance mechanisms must be present in some clinical isolates...
  62. ncbi Identification of five human and mammal associated Arcobacter species by a novel multiplex-PCR assay
    Laid Douidah
    Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
    J Microbiol Methods 80:281-6. 2010
    ..Furthermore, examination of the 23 S RNA gene of A. cryaerophilus revealed, besides large heterogeneity, the presence of intervening sequences ranging from 87 to 196 bp...
  63. ncbi Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity
    Leslie W Tari
    Trius Therapeutics, 6310 Nancy Ridge Dr, San Diego, CA 92121, USA
    Bioorg Med Chem Lett 23:1529-36. 2013
    The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication...
  64. pmc Alterations in topoisomerase IV and DNA gyrase in quinolone-resistant mutants of Mycoplasma hominis obtained in vitro
    C M Bebear
    Laboratoire de Bacteriologie, Universite Bordeaux 2, 33076 Bordeaux Cedex, France
    Antimicrob Agents Chemother 42:2304-11. 1998
    ..e., ciprofloxacin, norfloxacin, ofloxacin, or pefloxacin, respectively. These data indicate that in M. hominis DNA gyrase is the primary target of sparfloxacin whereas topoisomerase IV is the primary target of pefloxacin, ofloxacin, ..
  65. pmc Comparative in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes clinical isolates with alterat
    S Brisse
    Eijkman Winkler Institute, Utrecht University, 3584 CX, Utrecht, The Netherlands
    Antimicrob Agents Chemother 43:2051-5. 1999
    ..Irrespective of the alterations in GyrA and ParC proteins, clinafloxacin exhibited greater activity than all other fluoroquinolones tested against K. pneumoniae and E. aerogenes...
  66. ncbi Green tea catechins inhibit bacterial DNA gyrase by interaction with its ATP binding site
    Helena Gradisar
    Laboratory of Biotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia
    J Med Chem 50:264-71. 2007
    ..We determined that the catechins inhibit bacterial DNA gyrase by binding to the ATP binding site of the gyrase B subunit...
  67. ncbi A homogeneous, high-throughput fluorescence anisotropy-based DNA supercoiling assay
    Adam Shapiro
    AstraZeneca R and D Boston, Waltham, MA 2451, USA
    J Biomol Screen 15:1088-98. 2010
    ..The utility of this assay is demonstrated with relaxation of supercoiled plasmid by Escherichia coli topoisomerase I, supercoiling of relaxed plasmid by E. coli DNA gyrase, and inhibition of gyrase by fluoroquinolones and nalidixic acid.
  68. ncbi Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE), Part II: development of inhibitors with broad spectrum, Gram-negative antibacterial activity
    Micheal Trzoss
    Trius Therapeutics, 6310 Nancy Ridge Dr, San Diego, CA 92121, USA
    Bioorg Med Chem Lett 23:1537-43. 2013
    The structurally related bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as prime candidates for the development of broad spectrum antibacterial agents...
  69. ncbi Role of the CmeABC efflux pump in the emergence of fluoroquinolone-resistant Campylobacter under selection pressure
    Meiguan Yan
    Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA
    J Antimicrob Chemother 58:1154-9. 2006
    ..The objective of this study was to determine the contribution of the CmeABC efflux pump to the emergence of fluoroquinolone (FQ)-resistant mutants in Campylobacter jejuni under various levels of selection pressure...
  70. pmc Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV
    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, United Kingdom
    Antimicrob Agents Chemother 53:3822-31. 2009
    Quinazoline-2,4-diones, such as PD 0305970, are new DNA gyrase and topoisomerase IV (topo IV) inhibitors with potent activity against gram-positive pathogens, including quinolone-resistant isolates...
  71. ncbi Population-based investigation of fluoroquinolones resistant tuberculosis in rural eastern China
    Yi Hu
    Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Rd, Shanghai 200032, China
    Tuberculosis (Edinb) 91:238-43. 2011
    ..The relatively low level of clustering among FQ-resistant strains suggests most are acquired de novo, likely due to widespread FQ use...
  72. pmc 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, Hospital Clinic, 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...
  73. 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...
  74. ncbi Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis
    M Chatterji
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India 560012
    J Antimicrob Chemother 48:479-85. 2001
    Quinolones, coumarins, cyclothialidines, CcdB and microcin B17 inhibit DNA gyrase. Information regarding these various inhibitors comes from studies performed with the enzyme from Escherichia coli, and subsequent analyses have also ..
  75. pmc In vivo selection of Campylobacter isolates with high levels of fluoroquinolone resistance associated with gyrA mutations and the function of the CmeABC efflux pump
    Naidan Luo
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691, USA
    Antimicrob Agents Chemother 47:390-4. 2003
    ..These results reveal that Campylobacter is hypermutable in vivo under the selection pressure of FQ and highlight the need for the prudent use of FQ antibiotics...
  76. pmc Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra
    T Kocagoz
    Department of Medicine, University of California, San Francisco 94110, USA
    Antimicrob Agents Chemother 40:1768-74. 1996
    ..Because sparfloxacin is more active in vitro and selection of resistance appears to be less likely to occur, it may have important advantage over ofloxacin or ciprofloxacin for the treatment of tuberculosis...
  77. 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...
  78. 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...
  79. ncbi Selection and characterization of fluoroquinolone-resistant mutants of Campylobacter jejuni using enrofloxacin
    Sophie Payot
    UR86 de Pathologie Aviaire et Parasitologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
    Microb Drug Resist 8:335-43. 2002
    ..jejuni isolates. Results obtained during ciprofloxacin accumulation studies confirmed that efflux probably plays a minor role in fluoroquinolone resistance of C. jejuni...
  80. ncbi Characterization of pyrazinamide and ofloxacin resistance among drug resistant Mycobacterium tuberculosis isolates from Singapore
    Ann S G Lee
    Department of Clinical Research, Singapore General Hospital, Singapore
    Int J Infect Dis 6:48-51. 2002
    ..To evaluate rapid molecular approaches for the detection of pyrazinamide (PZA) and ofloxacin resistance, by screening 100 known drug-resistant Mycobacterium tuberculosis isolates...
  81. ncbi Antimicrobial effects of H4-(86-100), histogranin and related compounds--possible involvement of DNA gyrase
    Simon Lemaire
    Department of Molecular and Cellular Medicine, University of Ottawa, Canada
    FEBS J 275:5286-97. 2008
    ..the antimicrobial activities of H4-(86-100), HNr and compound 3, like those of quinolone antibiotics acting as DNA gyrase poisons, are potentiated by ATP (1 mM) and coumermycin A1 (a DNA gyrase-linked ATPase inhibitor) and blocked by ..
  82. pmc Enhancement of fluoroquinolone activity by C-8 halogen and methoxy moieties: action against a gyrase resistance mutant of Mycobacterium smegmatis and a gyrase-topoisomerase IV double mutant of Staphylococcus aureus
    T Lu
    Public Health Research Institute, 455 First Ave, New York, NY 10016, USA
    Antimicrob Agents Chemother 45:2703-9. 2001
    ....
  83. pmc Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year period
    Hong Bin Kim
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
    Antimicrob Agents Chemother 53:639-45. 2009
    ....
  84. ncbi Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and structure-activity relationships
    Paul S Charifson
    Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, Massachusetts 02139, USA
    J Med Chem 51:5243-63. 2008
    ..Bacterial DNA gyrase and topoisomerase IV are well-characterized clinically validated targets of the fluoroquinolone antibiotics ..
  85. pmc Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France
    Magali Garcia
    EA 4331 LITEC, Universite de Poitiers, CHU de Poitiers, Laboratoire de Bacteriologie Hygiene, Poitiers, France
    Antimicrob Agents Chemother 56:550-1. 2012
    ....
  86. pmc Extending the definition of the GyrB quinolone resistance-determining region in Mycobacterium tuberculosis DNA gyrase for assessing fluoroquinolone resistance in M. tuberculosis
    Alix Pantel
    UPMC Université Paris, Laboratoire de Bacteriologie Hygiene, Paris, France
    Antimicrob Agents Chemother 56:1990-6. 2012
    ..is amino acid substitution within the quinolone resistance-determining region (QRDR) of the GyrA subunit of DNA gyrase, the sole FQ target in M. tuberculosis...
  87. pmc Molecular characterization of fluoroquinolone resistance in Mycobacterium tuberculosis: functional analysis of gyrA mutation at position 74
    Ricky W T Lau
    Department of Microbiology, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
    Antimicrob Agents Chemother 55:608-14. 2011
    ..A number of gyrA mutations (Glu21Gln, Ser95Thr, and Gly668Asp) were also characterized to be natural polymorphisms not associated with fluoroquinolone resistance...
  88. ncbi Molecular mechanisms of antibiotic resistance
    Gerard D Wright
    M G DeGroote Institute for Infectious Disease Research, McMaster University, 1200 Main St W, Hamilton, ON, Canada
    Chem Commun (Camb) 47:4055-61. 2011
    ..Understanding the chemical rationale and underpinnings of resistance is an essential component of our response to this clinical challenge...
  89. pmc Are all the DNA gyrase mutations found in Mycobacterium leprae clinical strains involved in resistance to fluoroquinolones?
    Stephanie Matrat
    Universite Pierre et Marie Curie Paris 6, Paris, France
    Antimicrob Agents Chemother 52:745-7. 2008
    ..We demonstrated that the gyrA mutations leading to G89C or A91V confer fluoroquinolone resistance whereas the gyrB mutation leading to D205N does not...
  90. pmc The role of Ca²⁺ in the activity of Mycobacterium tuberculosis DNA gyrase
    Shantanu Karkare
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK
    Nucleic Acids Res 40:9774-87. 2012
    b>DNA gyrase is the only type II topoisomerase in Mycobacterium tuberculosis and needs to catalyse DNA supercoiling, relaxation and decatenation reactions in order to fulfil the functions normally carried out by gyrase and DNA topoisomerase ..
  91. pmc Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains defines an early step in the supercoiling cycle
    Martin A Lanz
    University of Basel, Biozentrum, Biophysical Chemistry, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Nucleic Acids Res 39:9681-94. 2011
    b>DNA gyrase catalyzes ATP-dependent negative supercoiling of DNA in a strand passage mechanism...
  92. pmc Role of efflux pumps and topoisomerase mutations in fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli
    Beilei Ge
    Department of Nutrition and Food Science, 0112 Skinner Building, University of Maryland, College Park, MD 20742, USA
    Antimicrob Agents Chemother 49:3347-54. 2005
    Point mutations in the topoisomerase (DNA gyrase A) gene are known to be associated with fluoroquinolone resistance in Campylobacter...
  93. ncbi A high-throughput assay for DNA topoisomerases and other enzymes, based on DNA triplex formation
    Matthew R Burrell
    Department of Biological Chemistry, John Innes Centre, Norwich, UK
    Methods Mol Biol 613:257-66. 2010
    ..The assay is performed in microtitre plates and can be adapted to high-throughput screening of libraries of potential inhibitors of topoisomerases including bacterial DNA gyrase.
  94. pmc 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...
  95. 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...
  96. 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...
  97. pmc 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...
  98. pmc 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...
  99. pmc 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...
  100. pmc 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...
  101. 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 ..

Research Grants53

  1. Plasmid-Mediated Quinolone Resistance
    George A Jacoby; Fiscal Year: 2013
    ..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 ..
  2. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth N Kreuzer; Fiscal Year: 2012
    ..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 ..
  3. Ciprofloxacin enhances DNA repair capacity after radiation combined injury
    JULIANN GONG KIANG; Fiscal Year: 2012
    ..CIP works by inhibiting bacterial DNA gyrase (bacterial topo II or topo IV), but has a slight inhibitory effects on eukaryotic topo II...
  4. Novel fluoroquinolones for killing dormant Mycobacterium tuberculosis
    Xilin Zhao; Fiscal Year: 2013
    ..As part of their mechanism of action, quinolones trap DNA gyrase as drug-enzyme-DNA complexes in which the DNA is broken but held together by protein...
  5. Developing and Testing a Novel Geometric Model of Protein Adaptation
    DANIEL MICHAEL WEINREICH; Fiscal Year: 2013
    ..resistance mutations are often in dihydrofolate reductase, quinoline resistance mutations are often in DNA gyrase, rifamycin resistance mutations are often in RNA polymerase)...
  6. DNA helicase and primase inhibitors for biodefense
    Donald T Moir; Fiscal Year: 2010
    ..inhibitor shares the bicyclic ring of the clinically-proven aminocoumarin scaffold;however, it does not inhibit DNA gyrase or the binding of ATP to helicase...
  7. High Throughput Screens for Malaria Topoisomerases
    Pradipsinh K Rathod; Fiscal Year: 2013
    ..In this project application, we will express all P. falciparum and P. vivax candidate topoisomerase and DNA gyrase gene products, test their catalytic activity, purify them to homogeneity, and develop miniaturized efficient ..
  8. Gyrase B Inhibitors for Mycobacterium Tuberculosis
    Peter B Madrid; Fiscal Year: 2013
    ..The inclusion of a fluoroquinoline antibiotic, which targets the A subunit of DNA gyrase (GyrA), into combination therapy regimens has improved culture conversion rates in clinical trials, indicating a ..
  9. Antibacterial Agents that Restrict the Emergence of Resistance
    ROBERT JOHN KERNS; Fiscal Year: 2013
    ..The long-term goal of this research program is to develop new DNA gyrase inhibitors that are highly effective anti-tuberculosis (TB) agents with susceptible, multidrug-resistant, ..
  10. Testing and improving alchemical techniques for predicting protein-ligand binding
    DAVID LOWELL MOBLEY; Fiscal Year: 2012
    ..with substantial analysis and additional calculations;and (3) compute binding affinities of an extensive set of DNA gyrase inhibitors, testing against experimental data and rationalizing observed trends...
  11. CHROMATIN HISTONE MODIFICATIONS AND HMG PROTEINS
    EDWIN BRADBURY; Fiscal Year: 1992
    ..e. it may behave as a DNA gyrase. It may also be a mechanism for localizing transient DNA supercoiling between unfolding and refolding of 34 nm ..
  12. Impact of Fluoroquinolone resistance on Pseudomonas virulence and patient outcome
    Annie Wong Beringer; Fiscal Year: 2009
    ..g. DNA gyrase) which simultaneously confer resistance to FQ and upregulate TTSS gene transcription due to changes in DNA ..
  13. Ciprofloxacin enhances DNA repair capacity after radiation combined injury
    JULIANN KIANG; Fiscal Year: 2009
    ..CIP works by inhibiting bacterial DNA gyrase (bacterial topo II or topo IV), but has a slight inhibitory effects on eukaryotic topo II...
  14. ROLE OF RIBONUCLEOTIDE REDUCTASE IN DNA REPLICATION
    C Greenberg; Fiscal Year: 1990
    ..However, suppression by gene 39 mutants is prevented by a mutation in the host gyrB gene (DNA gyrase)...
  15. EXTRACHROMOSOMAL DNA ESTABLISHMENT IN PSEUDOMONAS
    Robert Miller; Fiscal Year: 1980
    ..Several enzymes which will be investigated are: (1) adenylate cyclase, (2) DNA gyrase, (3) Pseudomonas exonuclease V and (4) Pseudomonas exonuclease I...
  16. Quinolone Action During Mycobacterial Growth Arrest
    Karl Drlica; Fiscal Year: 2006
    ..b>DNA gyrase mutants have been identified that enhance this minor pathway...
  17. STRUCTURE OF INTERPHASE AND METAPHASE CHROMOSOMES
    MARTIN GOROVSKY; Fiscal Year: 1990
    ..In particular, we shall purify and characterize the eucaryotic DNA gyrase, an enzyme which plays a key role in the production and maintenance of the torsionally strained supercoils in ..
  18. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2007
    ..abstract_text> ..
  19. FOURTH CONFERENCE ON DNA TOPOISOMERASES IN THERAPY
    Milan Potmesil; Fiscal Year: 1992
    ..discuss not only anticancer agents and their target DNA topoisomerase I or II, but also a closely related enzyme DNA gyrase targeted by quinolones and related drugs...
  20. DISCOVERY OF NOVEL FUNGICIDAL AGENTS
    LESTER MITSCHER; Fiscal Year: 1992
    ..Our experiences in the design and synthesis of bacterial (DNA Gyrase) and mammalian (topo-II) topoisomerase inhibitors and study of their pharmacokinetics and in vivo activities ..
  21. EVOLUTIONARY EFFECTS OF MAJOR MUTATIONS
    Frederick Cohan; Fiscal Year: 1992
    ..characterized proteins in Bacillus subtilis (including ribosomal proteins and subunits of RNA polymerase and DNA gyrase)...
  22. QUINOLONE RESISTANCE MECHANISMS IN STAPHYLOCOCCUS AUREUS
    David Hooper; Fiscal Year: 2007
    ..abstract_text> ..
  23. Plasmid-Mediated Quinolone Resistance
    George Jacoby; Fiscal Year: 2007
    ..We discovered a plasmid-encoded protein termed Qnr that protects DNA gyrase from quinolone inhibition...
  24. 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...
  25. Bacterial DnaA Initiator Protein: A Target for Novel Antibiotics
    Michelle Butler; Fiscal Year: 2008
    ..This proposal describes a new type of screening assay that can identify inhibitors of DnaA, a previously unexploited protein involved in the initiation of DNA synthesis. [unreadable] [unreadable] [unreadable]..
  26. A NOVEL THERAPY FOR RESPIRATORY SYNCYTIAL VIRUS
    Michelle Butler; Fiscal Year: 2003
    ..The goal is to file an IND within three years of initiation of the Phase I SBIR studies. ..
  27. Development of a HTS system:topoisomerase targets (RMI)
    Yuk Ching Tse Dinh; Fiscal Year: 2004
    ..The screening system should also be applicable for targeting topoisomerases in pathogenic bacteria relevant for biodefense. ..
  28. Resistant E.coli in Humans and Poultry
    James Johnson; Fiscal Year: 2005
    ..Does the research address a current and compelling problem of antimicrobial resistance that is of high public health importance and for which research is needed? [yes]. ..
  29. DEVELOPMENT OF INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS DNA REPLICATION
    Michelle Butler; Fiscal Year: 2007
    ..We will begin with 2 essential DNA replication targets-DNA polymerase III (pol III) and DNA gyrase. Microbiotix has considerable experience with the preparation and assay of these enzymes in low G:C Gram+ ..
  30. DEVELOPMENT OF SCREENS FOR BACILLUS ANTHRACIS TARGETS
    Michelle Butler; Fiscal Year: 2005
    ..In Phase II, we will optimize the most promising compounds to develop novel leads and candidate drugs for pre-clinical testing in animal models of infection. ..
  31. BACTERIAL DNA POLYMERASES: TARGET FOR NOVEL ANTIBIOTICS
    Michelle Butler; Fiscal Year: 2005
    ..The SAR development and in vitro and in vivo characterization studies are the subject of this Phase II application. ..
  32. Type III Secretion Inhibitors for Anti-Infective Therapy
    Donald Moir; Fiscal Year: 2007
    ..aeruginosa TTSS; (3) Screen a diverse compound library to identify and validate TTSS inhibitors; and (4) Prioritize validated screening hits for in vitro potency, mechanism, spectrum, and selectivity. [unreadable] [unreadable]..
  33. Direct analysis of fork blockage and DNA repair in vivo
    Kenneth Kreuzer; Fiscal Year: 2003
    ..If the system is validated, many other kinds of DNA damage can presumably be analyzed in-future studies. ..
  34. DNA helicase and primase inhibitors for biodefense
    Donald Moir; Fiscal Year: 2006
    ..Finally, compounds will be tested for lack of toxicity to mammalian cells in culture, and lack of activity against eukaryotic polymerase alpha and helicase, resulting in a collection of validated hits. ..
  35. Bartonella Inhibitory Factor for Endothelial Cell Growth
    MICHAEL MINNICK; Fiscal Year: 2002
    ..abstract_text> ..
  36. Sensing Biowarfare Agents by Surface Enhanced Raman
    Donald Moir; Fiscal Year: 2005
    ....
  37. Hemin Receptor Gene Family of Bartonella quintana
    MICHAEL MINNICK; Fiscal Year: 2006
    ..abstract_text> ..
  38. ANTITUMOR AGENTS AND THE BACTERIOPHAGE T4 TOPOISOMERASE
    Kenneth Kreuzer; Fiscal Year: 2001
    ....
  39. INITIATION OF DNA REPLICATION IN THE PHAGE T4 SYSTEM
    Kenneth Kreuzer; Fiscal Year: 2005
    ....
  40. BACTERIAL DNA HELICASES: TARGETS FOR NOVEL ANTIBIOTICS
    Marjorie Barnes; Fiscal Year: 2005
    ..In Phase II, we will characterize the mechanism of action of the validated hits in more detail and optimize the most promising of these structures utilizing a rational drug design approach to develop antibacterial lead compounds. ..
  41. QUINOLONE RESISTANCE IN NOSOCOMIAL URINARY INFECTIONS
    Ebbing Lautenbach; Fiscal Year: 2004
    ....
  42. C. difficile Toxin Membrane Test with Magnetic Particles
    ROBERT CARMAN; Fiscal Year: 2004
    ..perfringens enterotoxin, another cause of AAD. The technology developed in this project will be widely applicable for the development of new highly sensitive stool antigen tests. ..
  43. Duke PREP: Minority Recruitment into Biomedical Sciences
    Kenneth Kreuzer; Fiscal Year: 2007
    ..The PREP scholars will be encouraged to take advantage of the full two-year experience, as long as they perform at an acceptable level and maintain an interest in pursuing a career in science. ..
  44. Saccharide-Based Effectors of Cationic Antimicrobial Peptides
    Robert Kerns; Fiscal Year: 2007
    ..We are also investigating if certain types of therapeutic agents inhibit antibacterial activity of the antimicrobial peptides. [unreadable] [unreadable] [unreadable]..
  45. Clinical Impact of Quinolone-Resistant E.coli carriage
    Ebbing Lautenbach; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  46. Hunter Killer Peptides: Membrane Interactions and Receptor Binding
    Leigh Plesniak; Fiscal Year: 2007
    ..A second HKP that kills white fat tissue reduces fatty deposits and has a positive impact on glucose metabolism, reducing symptoms of diabetes. [unreadable] [unreadable] [unreadable]..
  47. PAH/Metal exposure and effects assessment in Chattanooga
    Sean Richards; Fiscal Year: 2004
    ..5) Quantify the potential for the residents of South Chattanooga to be exposed and affected by PAHs and metals present in area soil by using the data generated in this study in a probabilistic risk assessment. ..
  48. Novel Targets for Treatment of Pseudomonas aeruginosa
    Philip Lister; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  49. Mucin-degrading microflora for prophylactic antibiotics
    ROBERT CARMAN; Fiscal Year: 2008
    ..difficile, and reduces the incidence of C. difficile- induced antibiotic-associated diarrhea. [unreadable] [unreadable] [unreadable]..
  50. Discovery of B. pseudomallei Therapeutics for Biodefense
    Donald Moir; Fiscal Year: 2008
    ..pseudomallei targets. In Phase III, a potent, safe, orally active B. pseudomallei inhibitor will be advanced into IND enabling toxicology and safety pharmacology studies and file an IND. [unreadable] [unreadable] [unreadable]..
  51. Novel Application of Infection Control Strategies to Limit Transmission of ESBL'S
    Ebbing Lautenbach; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  52. Quinolone resistant E coli in long term care facilities
    Ebbing Lautenbach; Fiscal Year: 2009
    ..abstract_text> ..
  53. Basal Ig Signaling and Receptor Editing
    Michael Farrar; Fiscal Year: 2009
    ..abstract_text> ..