|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 42, 27668-27677, October 16, 1998
From the Department of Molecular and Cell Biology, University of
California, Berkeley, California 94720-3204
Topoisomerase IV (Topo IV) is a mediator of
quinolone toxicity in bacteria. In this work, we demonstrate that
norfloxacin, a model quinolone, converts Escherichia coli
Topo IV into a poisonous adduct on DNA as opposed to inhibiting
topoisomerase activity. Norfloxacin inhibition of Topo IV induces a
slow decline in DNA synthesis that parallels cell death. Treatment of
cells with a lethal concentration of the antibacterial did not block
chromosome segregation, the phenotype of catalytic inhibition of Topo
IV. Instead, norfloxacin causes DNA damage, as evidenced by the
induction of the SOS pathway for DNA repair; the increase in
susceptibility to the drug by mutations in genes for DNA repair
pathways including recA, recB, and
uvrD; and the efficient detergent-induced linearization of
plasmid DNA in drug-treated cells. Wild-type and drug-resistant alleles
of Topo IV are co-dominant, but we find that mutations in
recA, seqA, or gyrB result in
unconditional dominance of the sensitive allele, the characteristic of
a poisoning mode of inhibition. These mutations either compromise
chromosome integrity or force Topo IV to play a more active role in DNA
unlinking in front of the replication fork. We interpret our results in
terms of distinct but complementary roles of Topo IV and gyrase in DNA
replication.
The Mechanism of Inhibition of Topoisomerase IV by Quinolone
Antibacterials
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Kang and M. J. Blaser Repair and Antirepair DNA Helicases in Helicobacter pylori J. Bacteriol., June 15, 2008; 190(12): 4218 - 4224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Drlica, M. Malik, R. J. Kerns, and X. Zhao Quinolone-Mediated Bacterial Death Antimicrob. Agents Chemother., February 1, 2008; 52(2): 385 - 392. [Full Text] [PDF]
|
|
|
|
|
|
E. S. Pfeiffer and H. Hiasa Determination of the Primary Target of a Quinolone Drug and the Effect of Quinolone Resistance-Conferring Mutations by Measuring Quinolone Sensitivity Based on Its Mode of Action Antimicrob. Agents Chemother., September 1, 2007; 51(9): 3410 - 3412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Chung, P. J. McNamara, J. J. Campion, and M. E. Evans Mechanism-Based Pharmacodynamic Models of Fluoroquinolone Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother., September 1, 2006; 50(9): 2957 - 2965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-H. Hsu, M.-W. Chung, and T.-K. Li Distribution of gyrase and topoisomerase IV on bacterial nucleoid: implications for nucleoid organization Nucleic Acids Res., June 6, 2006; 34(10): 3128 - 3138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nuzzo and N. Zagorski In Memoriam: PNAS Editor-in-Chief Nicholas R. Cozzarelli (1938-2006) PNAS, April 18, 2006; 103(16): 6078 - 6080. [Full Text] [PDF]
|
|
|
|
|
|
J. Strahilevitz, A. Robicsek, and D. C. Hooper Role of the Extended {alpha}4 Domain of Staphylococcus aureus Gyrase A Protein in Determining Low Sensitivity to Quinolones Antimicrob. Agents Chemother., February 1, 2006; 50(2): 600 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Marrer, A. T. Satoh, M. M. Johnson, L. J. V. Piddock, and M. G. P. Page Global Transcriptome Analysis of the Responses of a Fluoroquinolone-Resistant Streptococcus pneumoniae Mutant and Its Parent to Ciprofloxacin Antimicrob. Agents Chemother., January 1, 2006; 50(1): 269 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Galbraith, A. C. Ng, B. J. Eggers, C. R. Kuchel, C. H. Eggers, and D. S. Samuels parC Mutations in Fluoroquinolone-Resistant Borrelia burgdorferi Antimicrob. Agents Chemother., October 1, 2005; 49(10): 4354 - 4357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Korzheva, T. A. Davies, and R. Goldschmidt Novel Ser79Leu and Ser81Ile Substitutions in the Quinolone Resistance-Determining Regions of ParC Topoisomerase IV and GyrA DNA Gyrase Subunits from Recent Fluoroquinolone-Resistant Streptococcus pneumoniae Clinical Isolates Antimicrob. Agents Chemother., June 1, 2005; 49(6): 2479 - 2486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kang, S. Huang, and M. J. Blaser Structural and Functional Divergence of MutS2 from Bacterial MutS1 and Eukaryotic MSH4-MSH5 Homologs J. Bacteriol., May 15, 2005; 187(10): 3528 - 3537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gruger, J. L. Nitiss, A. Maxwell, E. L. Zechiedrich, P. Heisig, S. Seeber, Y. Pommier, and D. Strumberg A Mutation in Escherichia coli DNA Gyrase Conferring Quinolone Resistance Results in Sensitivity to Drugs Targeting Eukaryotic Topoisomerase II Antimicrob. Agents Chemother., December 1, 2004; 48(12): 4495 - 4504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kang, D. Tavakoli, A. Tschumi, R. A. Aras, and M. J. Blaser Effect of Host Species on RecG Phenotypes in Helicobacter pylori and Escherichia coli J. Bacteriol., November 15, 2004; 186(22): 7704 - 7713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kang, J. S. Han, J. H. Park, K. Skarstad, and D. S. Hwang SeqA Protein Stimulates the Relaxing and Decatenating Activities of Topoisomerase IV J. Biol. Chem., December 5, 2003; 278(49): 48779 - 48785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ince and D. C. Hooper Quinolone Resistance Due to Reduced Target Enzyme Expression J. Bacteriol., December 1, 2003; 185(23): 6883 - 6892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Shea and H. Hiasa The RuvAB Branch Migration Complex Can Displace Topoisomerase IV{middle dot}Quinolone{middle dot}DNA Ternary Complexes J. Biol. Chem., November 28, 2003; 278(48): 48485 - 48490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Allen, G. W. Kaatz, and M. J. Rybak Activities of Mutant Prevention Concentration-Targeted Moxifloxacin and Levofloxacin against Streptococcus pneumoniae in an In Vitro Pharmacodynamic Model Antimicrob. Agents Chemother., August 1, 2003; 47(8): 2606 - 2614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yang, S. R. Clayton, and E. L. Zechiedrich Relative contributions of the AcrAB, MdfA and NorE efflux pumps to quinolone resistance in Escherichia coli J. Antimicrob. Chemother., March 1, 2003; 51(3): 545 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hiasa, M. E. Shea, C. M. Richardson, and M. N. Gwynn Staphylococcus aureus Gyrase-Quinolone-DNA Ternary Complexes Fail to Arrest Replication Fork Progression in Vitro. EFFECTS OF SALT ON THE DNA BINDING MODE AND THE CATALYTIC ACTIVITY OF S. AUREUS GYRASE J. Biol. Chem., February 28, 2003; 278(10): 8861 - 8868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Minnick, Z. R. Wilson, L. S. Smitherman, and D. S. Samuels gyrA Mutations in Ciprofloxacin-Resistant Bartonella bacilliformis Strains Obtained In Vitro Antimicrob. Agents Chemother., January 1, 2003; 47(1): 383 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ince, X. Zhang, L. C. Silver, and D. C. Hooper Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Garenoxacin (BMS-284756, T-3811ME), a New Desfluoroquinolone Antimicrob. Agents Chemother., November 1, 2002; 46(11): 3370 - 3380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tominaga, K. Higuchi, N. Hamasaki, M. Hamaguchi, T. Takashima, T. Tanigawa, T. Watanabe, Y. Fujiwara, Y. Tezuka, T. Nagaoka, et al. In vivo action of novel alkyl methyl quinolone alkaloids against Helicobacter pylori J. Antimicrob. Chemother., October 1, 2002; 50(4): 547 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Mahmoud. A. Yassien, H. E. Ewis, C.-D. Lu, and A. T. Abdelal Molecular Cloning and Characterization of the Salmonella enterica Serovar Paratyphi B rma Gene, Which Confers Multiple Drug Resistance in Escherichia coli Antimicrob. Agents Chemother., February 1, 2002; 46(2): 360 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, X. Zhao, and K. Drlica Selection of Streptococcus pneumoniae Mutants Having Reduced Susceptibility to Moxifloxacin and Levofloxacin Antimicrob. Agents Chemother., February 1, 2002; 46(2): 522 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-S. Pan, G. Yague, and L. M. Fisher Quinolone Resistance Mutations in Streptococcus pneumoniae GyrA and ParC Proteins: Mechanistic Insights into Quinolone Action from Enzymatic Analysis, Intracellular Levels, and Phenotypes of Wild-Type and Mutant Proteins Antimicrob. Agents Chemother., November 1, 2001; 45(11): 3140 - 3147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Khodursky, B. J. Peter, M. B. Schmid, J. DeRisi, D. Botstein, P. O. Brown, and N. R. Cozzarelli Analysis of topoisomerase function in bacterial replication fork movement: Use of DNA microarrays PNAS, August 15, 2000; 97(17): 9419 - 9424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Fournier, X. Zhao, T. Lu, K. Drlica, and D. C. Hooper Selective Targeting of Topoisomerase IV and DNA Gyrase in Staphylococcus aureus: Different Patterns of Quinolone- Induced Inhibition of DNA Synthesis Antimicrob. Agents Chemother., August 1, 2000; 44(8): 2160 - 2165. [Abstract] [Full Text]
|
|
|
|
|
|
C. Bisognano, P. Vaudaux, P. Rohner, D. P. Lew, and D. C. Hooper Induction of Fibronectin-Binding Proteins and Increased Adhesion of Quinolone-Resistant Staphylococcus aureus by Subinhibitory Levels of Ciprofloxacin Antimicrob. Agents Chemother., June 1, 2000; 44(6): 1428 - 1437. [Abstract] [Full Text]
|
|
|
|
|
|
M. E. Shea and H. Hiasa Distinct Effects of the UvrD Helicase on Topoisomerase- Quinolone-DNA Ternary Complexes J. Biol. Chem., May 5, 2000; 275(19): 14649 - 14658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Zechiedrich, A. B. Khodursky, S. Bachellier, R. Schneider, D. Chen, D. M. J. Lilley, and N. R. Cozzarelli Roles of Topoisomerases in Maintaining Steady-state DNA Supercoiling in Escherichia coli J. Biol. Chem., March 10, 2000; 275(11): 8103 - 8113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hong and K. N. Kreuzer An Antitumor Drug-Induced Topoisomerase Cleavage Complex Blocks a Bacteriophage T4 Replication Fork In Vivo Mol. Cell. Biol., January 15, 2000; 20(2): 594 - 603. [Abstract] [Full Text]
|
|
|
|
|
|
V. E. Anderson, R. P. Zaniewski, F. S. Kaczmarek, T. D. Gootz, and N. Osheroff Quinolones Inhibit DNA Religation Mediated by Staphylococcus aureus Topoisomerase IV. CHANGES IN DRUG MECHANISM ACROSS EVOLUTIONARY BOUNDARIES J. Biol. Chem., December 10, 1999; 274(50): 35927 - 35932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Shea and H. Hiasa Interactions between DNA Helicases and Frozen Topoisomerase IV-Quinolone-DNA Ternary Complexes J. Biol. Chem., August 6, 1999; 274(32): 22747 - 22754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-S. Pan and L. M. Fisher Streptococcus pneumoniae DNA Gyrase and Topoisomerase IV: Overexpression, Purification, and Differential Inhibition by Fluoroquinolones Antimicrob. Agents Chemother., May 1, 1999; 43(5): 1129 - 1136. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |