Genomes and Genes
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.
Publications356 found, 100 shown here
- The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaksAndrew 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 ..
- DNA topoisomerases: harnessing and constraining energy to govern chromosome topologyAllyn 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....
- Exploiting bacterial DNA gyrase as a drug target: current state and perspectivesFrédéric Collin
Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK
Appl Microbiol Biotechnol 92:479-97. 2011b>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...
- Origin and evolution of DNA topoisomerasesPatrick Forterre
Institut de Genetique et Microbiologie, UMR8621, Universite Paris Sud 11, Bat 400 409, 91405 Orsay Cedex, France
Biochimie 89:427-46. 2007....
- Type IIA topoisomerase inhibition by a new class of antibacterial agentsBenjamin 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 ..
- Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developmentsKatie 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....
- Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protectionJoaquim 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...
- Interplay in the selection of fluoroquinolone resistance and bacterial fitnessLinda L Marcusson
Microbiology Programme, Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden
PLoS Pathog 5:e1000541. 2009Fluoroquinolones are antibacterial drugs that inhibit DNA Gyrase and Topoisomerase IV. These essential enzymes facilitate chromosome replication and RNA transcription by regulating chromosome supercoiling...
- ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyraseYong 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...
- Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutationsH 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...
- ATP binding controls distinct structural transitions of Escherichia coli DNA gyrase in complex with DNAAakash Basu
Department of Applied Physics, Stanford University, Stanford, California, USA
Nat Struct Mol Biol 19:538-46, S1. 2012b>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...
- Rates of gyrase supercoiling and transcription elongation control supercoil density in a bacterial chromosomeNikolay 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...
- 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 efficiencyElsa 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...
- Topological insulators inhibit diffusion of transcription-induced positive supercoils in the chromosome of Escherichia coliLaurent 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...
- Mechanism of plasmid-mediated quinolone resistanceJohn H Tran
Infectious Disease Department, Lahey Clinic, Burlington, MA 01805, USA
Proc Natl Acad Sci U S A 99:5638-42. 2002Quinolones 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...
- A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering systemFernanda 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...
- Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pyloriJacques 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...
- New insights into fluoroquinolone resistance in Mycobacterium tuberculosis: functional genetic analysis of gyrA and gyrB mutationsSeidu 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...
- Prevalence of mutations within the quinolone resistance-determining region of gyrA, gyrB, parC, and parE and association with antibiotic resistance in quinolone-resistant Salmonella entericaDeborah 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...
- Distribution of fluoroquinolone MICs in Helicobacter pylori strains from Korean patientsJung 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...
- A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyraseMarcus J Edwards
Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK
Science 326:1415-8. 2009Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme...
- Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibioticsSilke Alt
Pharmaceutical Biology, Pharmaceutical Institute, University of Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
J Antimicrob Chemother 66:2061-9. 2011Aminocoumarin 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 ..
- Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A nonconserved acidic C-terminal tail modulates Escherichia coli gyrase activityElsa 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...
- 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 specificityS 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...
- Application of a novel microtitre plate-based assay for the discovery of new inhibitors of DNA gyrase and DNA topoisomerase VIJames 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...
- Comparative phylogenies of Burkholderia, Ralstonia, Comamonas, Brevundimonas and related organisms derived from rpoB, gyrB and rrs gene sequencesLineda 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...
- Cellulose degradation by micromonosporas recovered from freshwater lakes and classification of these actinomycetes by DNA gyrase B gene sequencingAlexandre 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...
- DNA gyrase inhibition assays are necessary to demonstrate fluoroquinolone resistance secondary to gyrB mutations in Mycobacterium tuberculosisAlix Pantel
UPMC Universite Paris 06, ER5, EA 1541, Laboratoire de Bacteriologie Hygiene, F 75005 Paris, France
Antimicrob Agents Chemother 55:4524-9. 2011The main mechanism of fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis is mutation in DNA gyrase (GyrA(2)GyrB(2)), especially in gyrA...
- Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistanceHyun 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)...
- 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 assaySoumitesh 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...
- Fluoroquinolone resistance in Mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposureJann 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...
- A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase functionAllyn 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...
- 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 sequencingRuiru 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...
- Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatmentSilke 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...
- Prevalence of primary fluoroquinolone resistance among clinical isolates of Helicobacter pylori at a University Hospital in Southern TaiwanKuei 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...
- Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine modelJulien 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...
- Quinolone resistance in Escherichia coli from Accra, GhanaSreela 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...
- Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyraseJérémie Piton
Unité de Dynamique Structurale des Macromolécules, Departement de Biologie Structurale et Chimie, Institut Pasteur, Paris, France
PLoS ONE 5:e12245. 2010Mycobacterium 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 ..
- Reduction of the fitness burden of quinolone resistance in Pseudomonas aeruginosaElisabeth 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...
- Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigationGuangsen 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. 2009b>DNA gyrase is an indispensible marvelous molecular machine in manipulating the DNA topology for the prokaryotes...
- First functional characterization of a singly expressed bacterial type II topoisomerase: the enzyme from Mycobacterium tuberculosisAlexandra 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...
- gyrA mutations associated with fluoroquinolone resistance in eight species of EnterobacteriaceaeL 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...
- Vibrio cholerae ParE2 poisons DNA gyrase via a mechanism distinct from other gyrase inhibitorsJie 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. 2010b>DNA gyrase is an essential bacterial enzyme required for the maintenance of chromosomal DNA topology...
- Fluoroquinolone resistance in Mycobacterium tuberculosis and mutations in gyrA and gyrBAndrea 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...
- Evolutionary history of Salmonella typhiPhilippe 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...
- Mechanochemical analysis of DNA gyrase using rotor bead trackingJeff Gore
Department of Physics, University of California, Berkeley, California 94720, USA
Nature 439:100-4. 2006b>DNA gyrase is a molecular machine that uses the energy of ATP hydrolysis to introduce essential negative supercoils into DNA...
- Molecular characterization of ciprofloxacin-resistant Salmonella enterica serovar Typhi and Paratyphi A causing enteric fever in IndiaR 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...
- Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis: functional analysis of mutant enzymesAlexandra 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. 2006Mutations in the DNA gyrase GyrA2GyrB2 complex are associated with resistance to quinolones in Mycobacterium tuberculosis...
- Nucleotide binding to DNA gyrase causes loss of DNA wrapJonathan G Heddle
Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK
J Mol Biol 337:597-610. 2004b>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)...
- DNA-induced narrowing of the gyrase N-gate coordinates T-segment capture and strand passageAirat Gubaev
Institute for Physical Chemistry, University of Muenster, Corrensstrasse 30, D 48149 Muenster, Germany
Proc Natl Acad Sci U S A 108:14085-90. 2011b>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...
- gyrB as a phylogenetic discriminator for members of the Bacillus anthracis-cereus-thuringiensis groupMyron 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...
- Drug-sensing hydrogels for the inducible release of biopharmaceuticalsMartin 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...
- gyrA and gyrB gene mutation in ciprofloxacin-resistant Mycobacterium massiliense clinical isolates from Southern BrazilFernanda 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...
- DNA gyrase and topoisomerase IV mutations associated with fluoroquinolone resistance in Proteus mirabilisL 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...
- GyrB sequence analysis and MALDI-TOF MS as identification tools for plant pathogenic ClavibacterJoanna 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...
- Cloning and characterization of the parC and parE genes of Streptococcus pneumoniae encoding DNA topoisomerase IV: role in fluoroquinolone resistanceX 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...
- Functional characterisation of mycobacterial DNA gyrase: an efficient decatenaseU H Manjunatha
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India
Nucleic Acids Res 30:2144-53. 2002A 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 ..
- Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitorsMatjaz Brvar
National Institute of Chemistry, Laboratory for Biocomputing and Bioinformatics, 1001 Ljubljana, Slovenia
J Med Chem 55:6413-26. 2012Bacterial DNA gyrase is a well-established and validated target for the development of novel antibacterials...
- Mechanisms of fluoroquinolone resistance in Escherichia coli isolates from food-producing animalsMaria 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...
- 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. 2006As only the type II topoisomerase is capable of introducing negative supercoiling, DNA gyrase is involved in crucial cellular processes...
- Mechanisms accounting for fluoroquinolone resistance in Escherichia coli clinical isolatesSonia 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...
- Identification of five human and mammal associated Arcobacter species by a novel multiplex-PCR assayLaid 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...
- 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 activityLeslie W Tari
Trius Therapeutics, 6310 Nancy Ridge Dr, San Diego, CA 92121, USA
Bioorg Med Chem Lett 23:1529-36. 2013The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication...
- Alterations in topoisomerase IV and DNA gyrase in quinolone-resistant mutants of Mycoplasma hominis obtained in vitroC 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, ..
- 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 alteratS 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...
- Green tea catechins inhibit bacterial DNA gyrase by interaction with its ATP binding siteHelena 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...
- A homogeneous, high-throughput fluorescence anisotropy-based DNA supercoiling assayAdam 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.
- Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE), Part II: development of inhibitors with broad spectrum, Gram-negative antibacterial activityMicheal Trzoss
Trius Therapeutics, 6310 Nancy Ridge Dr, San Diego, CA 92121, USA
Bioorg Med Chem Lett 23:1537-43. 2013The 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...
- Role of the CmeABC efflux pump in the emergence of fluoroquinolone-resistant Campylobacter under selection pressureMeiguan 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...
- Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IVXiao 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. 2009Quinazoline-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...
- Population-based investigation of fluoroquinolones resistant tuberculosis in rural eastern ChinaYi 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...
- Relationship between mutations in the gyrA gene and quinolone resistance in clinical isolates of Corynebacterium striatum and Corynebacterium amycolatumJosep 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...
- Dissection of the nucleotide cycle of B. subtilis DNA gyrase and its modulation by DNAThomas 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...
- Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatisM Chatterji
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India 560012
J Antimicrob Chemother 48:479-85. 2001Quinolones, 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 ..
- In vivo selection of Campylobacter isolates with high levels of fluoroquinolone resistance associated with gyrA mutations and the function of the CmeABC efflux pumpNaidan 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...
- Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37RaT 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...
- Mutation characterization of gyrA and gyrB genes in levofloxacin-resistant Mycobacterium tuberculosis clinical isolates from Guangdong Province in ChinaXiaomao 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...
- Mechanisms of quinolone action and microbial responsePeter 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...
- Selection and characterization of fluoroquinolone-resistant mutants of Campylobacter jejuni using enrofloxacinSophie 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...
- Characterization of pyrazinamide and ofloxacin resistance among drug resistant Mycobacterium tuberculosis isolates from SingaporeAnn 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...
- Antimicrobial effects of H4-(86-100), histogranin and related compounds--possible involvement of DNA gyraseSimon 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 ..
- 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 aureusT Lu
Public Health Research Institute, 455 First Ave, New York, NY 10016, USA
Antimicrob Agents Chemother 45:2703-9. 2001....
- Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year periodHong Bin Kim
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
Antimicrob Agents Chemother 53:639-45. 2009....
- 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 relationshipsPaul 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 ..
- Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in FranceMagali Garcia
EA 4331 LITEC, Universite de Poitiers, CHU de Poitiers, Laboratoire de Bacteriologie Hygiene, Poitiers, France
Antimicrob Agents Chemother 56:550-1. 2012....
- Extending the definition of the GyrB quinolone resistance-determining region in Mycobacterium tuberculosis DNA gyrase for assessing fluoroquinolone resistance in M. tuberculosisAlix 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...
- Molecular characterization of fluoroquinolone resistance in Mycobacterium tuberculosis: functional analysis of gyrA mutation at position 74Ricky 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...
- Molecular mechanisms of antibiotic resistanceGerard 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...
- 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...
- The role of Ca²⁺ in the activity of Mycobacterium tuberculosis DNA gyraseShantanu Karkare
Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK
Nucleic Acids Res 40:9774-87. 2012b>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 ..
- Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains defines an early step in the supercoiling cycleMartin A Lanz
University of Basel, Biozentrum, Biophysical Chemistry, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
Nucleic Acids Res 39:9681-94. 2011b>DNA gyrase catalyzes ATP-dependent negative supercoiling of DNA in a strand passage mechanism...
- Role of efflux pumps and topoisomerase mutations in fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coliBeilei Ge
Department of Nutrition and Food Science, 0112 Skinner Building, University of Maryland, College Park, MD 20742, USA
Antimicrob Agents Chemother 49:3347-54. 2005Point mutations in the topoisomerase (DNA gyrase A) gene are known to be associated with fluoroquinolone resistance in Campylobacter...
- A high-throughput assay for DNA topoisomerases and other enzymes, based on DNA triplex formationMatthew 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.
- Solution structures of DNA-bound gyraseNicole M Baker
Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA
Nucleic Acids Res 39:755-66. 2011The DNA gyrase negative supercoiling mechanism involves the assembly of a large gyrase/DNA complex and conformational rearrangements coupled to ATP hydrolysis...
- Importance of the efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolidI 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...
- Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torqueMarcelo Nollmann
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
Nat Struct Mol Biol 14:264-71. 2007E. 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...
- Molecular characterization of ofloxacin-resistant Mycobacterium tuberculosis strains from RussiaIgor Mokrousov
Laboratory of Molecular Microbiology, St Petersburg Pasteur Institute, 197101 St Petersburg, Russia
Antimicrob Agents Chemother 52:2937-9. 2008..tuberculosis...
- Structural and biochemical analysis of the pentapeptide repeat protein EfsQnr, a potent DNA gyrase inhibitorSubray 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...
- The DNA-gate of Bacillus subtilis gyrase is predominantly in the closed conformation during the DNA supercoiling reactionAirat 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...
- The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects on DNA gyrase catalytic reactions and on the ternary gyrase-DNA-quinolone complexAudrey Merens
Universite Paris, IFR, Bacteriologie, Creteil, France
J Bacteriol 191:1587-94. 2009MfpA(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...
- The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode of inhibitionJ G Heddle
Department of Biochemistry, University of Leicester, Leicester, LE1 7RH, UK
J Mol Biol 307:1223-34. 2001Microcin 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 ..
- Plasmid-Mediated Quinolone ResistanceGeorge 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 ..
- Processing and consequences of DNA-protein crosslinks in E. coliKenneth 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 ..
- Ciprofloxacin enhances DNA repair capacity after radiation combined injuryJULIANN 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...
- Novel fluoroquinolones for killing dormant Mycobacterium tuberculosisXilin 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...
- Developing and Testing a Novel Geometric Model of Protein AdaptationDANIEL 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)...
- DNA helicase and primase inhibitors for biodefenseDonald 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...
- High Throughput Screens for Malaria TopoisomerasesPradipsinh 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 ..
- Gyrase B Inhibitors for Mycobacterium TuberculosisPeter 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 ..
- Antibacterial Agents that Restrict the Emergence of ResistanceROBERT 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, ..
- Testing and improving alchemical techniques for predicting protein-ligand bindingDAVID 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...
- CHROMATIN HISTONE MODIFICATIONS AND HMG PROTEINSEDWIN 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 ..
- Impact of Fluoroquinolone resistance on Pseudomonas virulence and patient outcomeAnnie Wong Beringer; Fiscal Year: 2009..g. DNA gyrase) which simultaneously confer resistance to FQ and upregulate TTSS gene transcription due to changes in DNA ..
- Ciprofloxacin enhances DNA repair capacity after radiation combined injuryJULIANN 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...
- ROLE OF RIBONUCLEOTIDE REDUCTASE IN DNA REPLICATIONC Greenberg; Fiscal Year: 1990..However, suppression by gene 39 mutants is prevented by a mutation in the host gyrB gene (DNA gyrase)...
- EXTRACHROMOSOMAL DNA ESTABLISHMENT IN PSEUDOMONASRobert 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...
- Quinolone Action During Mycobacterial Growth ArrestKarl Drlica; Fiscal Year: 2006..b>DNA gyrase mutants have been identified that enhance this minor pathway...
- STRUCTURE OF INTERPHASE AND METAPHASE CHROMOSOMESMARTIN 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 ..
- DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSISKarl Drlica; Fiscal Year: 2007..abstract_text> ..
- FOURTH CONFERENCE ON DNA TOPOISOMERASES IN THERAPYMilan 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...
- DISCOVERY OF NOVEL FUNGICIDAL AGENTSLESTER 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 ..
- EVOLUTIONARY EFFECTS OF MAJOR MUTATIONSFrederick Cohan; Fiscal Year: 1992..characterized proteins in Bacillus subtilis (including ribosomal proteins and subunits of RNA polymerase and DNA gyrase)...
- QUINOLONE RESISTANCE MECHANISMS IN STAPHYLOCOCCUS AUREUSDavid Hooper; Fiscal Year: 2007..abstract_text> ..
- Plasmid-Mediated Quinolone ResistanceGeorge Jacoby; Fiscal Year: 2007..We discovered a plasmid-encoded protein termed Qnr that protects DNA gyrase from quinolone inhibition...
- MECHANISMS OF TOPOISOMERASE POISONSHiroshi 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...
- Bacterial DnaA Initiator Protein: A Target for Novel AntibioticsMichelle 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]..
- A NOVEL THERAPY FOR RESPIRATORY SYNCYTIAL VIRUSMichelle Butler; Fiscal Year: 2003..The goal is to file an IND within three years of initiation of the Phase I SBIR studies. ..
- 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. ..
- Resistant E.coli in Humans and PoultryJames 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]. ..
- DEVELOPMENT OF INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS DNA REPLICATIONMichelle 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+ ..
- DEVELOPMENT OF SCREENS FOR BACILLUS ANTHRACIS TARGETSMichelle 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. ..
- BACTERIAL DNA POLYMERASES: TARGET FOR NOVEL ANTIBIOTICSMichelle Butler; Fiscal Year: 2005..The SAR development and in vitro and in vivo characterization studies are the subject of this Phase II application. ..
- Type III Secretion Inhibitors for Anti-Infective TherapyDonald 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]..
- Direct analysis of fork blockage and DNA repair in vivoKenneth Kreuzer; Fiscal Year: 2003..If the system is validated, many other kinds of DNA damage can presumably be analyzed in-future studies. ..
- DNA helicase and primase inhibitors for biodefenseDonald 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. ..
- Bartonella Inhibitory Factor for Endothelial Cell GrowthMICHAEL MINNICK; Fiscal Year: 2002..abstract_text> ..
- Sensing Biowarfare Agents by Surface Enhanced RamanDonald Moir; Fiscal Year: 2005....
- Hemin Receptor Gene Family of Bartonella quintanaMICHAEL MINNICK; Fiscal Year: 2006..abstract_text> ..
- ANTITUMOR AGENTS AND THE BACTERIOPHAGE T4 TOPOISOMERASEKenneth Kreuzer; Fiscal Year: 2001....
- INITIATION OF DNA REPLICATION IN THE PHAGE T4 SYSTEMKenneth Kreuzer; Fiscal Year: 2005....
- BACTERIAL DNA HELICASES: TARGETS FOR NOVEL ANTIBIOTICSMarjorie 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. ..
- QUINOLONE RESISTANCE IN NOSOCOMIAL URINARY INFECTIONSEbbing Lautenbach; Fiscal Year: 2004....
- C. difficile Toxin Membrane Test with Magnetic ParticlesROBERT 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. ..
- Duke PREP: Minority Recruitment into Biomedical SciencesKenneth 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. ..
- Saccharide-Based Effectors of Cationic Antimicrobial PeptidesRobert Kerns; Fiscal Year: 2007..We are also investigating if certain types of therapeutic agents inhibit antibacterial activity of the antimicrobial peptides. [unreadable] [unreadable] [unreadable]..
- Clinical Impact of Quinolone-Resistant E.coli carriageEbbing Lautenbach; Fiscal Year: 2007..unreadable] [unreadable]..
- Hunter Killer Peptides: Membrane Interactions and Receptor BindingLeigh 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]..
- PAH/Metal exposure and effects assessment in ChattanoogaSean 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. ..
- Novel Targets for Treatment of Pseudomonas aeruginosaPhilip Lister; Fiscal Year: 2008..unreadable] [unreadable] [unreadable] [unreadable]..
- Mucin-degrading microflora for prophylactic antibioticsROBERT CARMAN; Fiscal Year: 2008..difficile, and reduces the incidence of C. difficile- induced antibiotic-associated diarrhea. [unreadable] [unreadable] [unreadable]..
- Discovery of B. pseudomallei Therapeutics for BiodefenseDonald 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]..
- Novel Application of Infection Control Strategies to Limit Transmission of ESBL'SEbbing Lautenbach; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Quinolone resistant E coli in long term care facilitiesEbbing Lautenbach; Fiscal Year: 2009..abstract_text> ..
- Basal Ig Signaling and Receptor EditingMichael Farrar; Fiscal Year: 2009..abstract_text> ..