Chapter 2 : Mechanisms of Quinolone Action

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This chapter introduces the quinolones with a brief consideration of DNA topoisomerases and quinolone target preference. Throughout the chapter attention is given to fluoroquinolone structure. Recently discovered examples include the relaxation of supercoils associated with infection of cultured macrophages by serovar Typhimurium and with hydrogen peroxide treatment of . The bacterial topoisomerases are divided into three groups: type I (topoisomerases I and III), type II (gyrase and topoisomerase IV), and specialized topoisomerases (enzymes that catalyze transposition or integration/excision of bacteriophage DNA from the bacterial chromosome). A function of topoisomerase I is the topological destabilization of transcription-mediated R loops. Another is likely to be control of global supercoiling, since a defect that raises supercoiling also suppresses a mutation, a defect that has a global effect on chromosome condensation. Quinolone binding to these mutant gyrase-DNA complexes induces a conformational change that can be detected in the GyrB subunit by limited proteolysis. The location of the quinolone-gyrase-DNA complexes on the bacterial chromosome is likely to influence the potential damage that quinolones can cause. The bacteriostatic effects of the quinolones are now understood at a level sufficient to allow structure-function interpretations. From a clinical perspective, there is a need to identify safe compounds that rapidly kill bacteria, especially resistant mutants. However, further refinement could become an academic exercise if ways are not developed to slow the emergence of fluoroquinolone-resistant pathogens.

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2
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Figure 1

Structures of commonly studied fluroquinolones.

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2
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Figure 2

Model of supercoiling and relaxation by DNA gyrase. (a) The 43-kDa and 47-kDa regions of GyrB, along with the 64-kDa region of GyrA are shown as a tetramer. The 33-kDa C-terminal domains of GyrA are omitted for clarity, as is the DNA wrap around gyrase. Supercoiling occurs when gyrase either binds a G segment of DNA (a) or assembles onto the G segment (b). The resulting complex (c) is a substrate for quinolone binding. The ternary complex (c) cleaves DNA to form a cleavage complex (d). ATP binds to the 43-kDa domains of GyrB, causing them to close and capture the T segment of DNA (e). The T segment is transported through the break in the G segment and into the bottom cavity of gyrase (f). The break in the G segment is religated (g), and the T segment is then released from the bottom cavity through the exit gate in the enzyme (h). The exit gate closes, resetting the enzyme for a new round of supercoiling. Between capture of the T segment and resetting of the enzyme, ATP is hydrolyzed and released. The figure was provided by Dr. J. G. Heddle (John Innes Centre, Norwich, United Kingdom). Reprinted from reference 83 by courtesy of Marcel Dekker, Inc.

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2
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Figure 3

Structure of DNA gyrase GyrA59 dimer. The figure shows a ribbon representation (generated in RasMol) of the GyrA59 fragment ( ), courtesy of J.G. Heddle (John Innes Centre). The upper panel shows the entire GyrA59 dimer while the lower panel is an enlargement of the boxed region in the upper panel. Amino acids that change to confer quinolone resistance are indicated in black and by the amino acid numbers. Amino acid 51 is in helix 2, amino acid 67 is in helix 3, and amino acids 83 and 87 are in helix 4. The figure was adapted from reference 61. Arrows in the upper panel indicate the location of changes that increase illegitimate recombination and spontaneous induction of lambda prophage as described in reference 7.

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2
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Figure 4

Proposed quinolone binding site. Orientation of fluoroquinolones and GyrA oc-helix-4. a-Helix-4, adapted from the crystal structure of the breakage-reunion domain of the GyrA protein of ( ), is drawn parallel to the long axis of the fluoroquinolone. For clarity, amino acid numbers represent positions in the GyrA protein. (The experiments were performed with position 81 in the figure corresponds to 89 in Arrows indicate positions of an ethyl group that changes the identity of the most resistant mutant (see text). The figure was adapted from reference 150.

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2
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Figure 5

Effect of GyrA variation on susceptibility to fluoroquinolones. MIC was determined for two structurally similar fluoroquinolones with the indicated fluoroquinolone-resistant mutants of . (The changes in the GyrA variants are indicated by standard amino acid abbreviations with the letter preceeding the number indicating the wild-type amino acid and the letter following the number representing the variant; the numbers used correspond to those shown in Fig. 4 and represent positions numbered according to the GyrA protein.) Panel A utilized fluoroquinolone PD161144, which has an ethyl group attached to the C-7 ring nitrogen as indicated by an arrow in Fig. 4 . Panel B utilized fluoroquinolone PD161148, which has its ethyl group attached to a C-7 ring carbon adjacent to the nitrogen indicated in Fig. 4 . The figure was adapted from data presented in reference 150.

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2
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1. Ali, J ., , A. Jackson,, A. Howells,, and A. Maxwell. 1993. The43-kDa N-terminal fragment of the gyrase B protein hydrolysesATP and binds coumarin drugs. Biochemistry 32:27172724.
2. Ali, J . A.,, G. Orphanides,, and A. Maxwell. 1995. Nucleotidebinding to the 43-kilodalton N-terminal fragment of theDNA gyrase. Biochemistry 34:98019808.
3. Alovero, F.,, X.-S. Pan,, J . Morris,, R. Manzo,, and L. Fisher.1999. Engineering the specificity of antibacterial fluoroquinolones:benzenesulfonamide modifications at C-7 ofciprofloxacin change its primary target in Streptococcus pneumoniae from topoisomerase IV to gyrase. Antimicrob.Agents Chemother. 44:320325.
4. Anderson, V.,, T. Gootz,, and N. Osheroff. 1998.Topoisomerase IV catalysis and the mechanism of quinoloneaction.J. Biol. Chem. 274:1787917885.
5. Anderson, V.,, R. Zaniewski,, F. Raczmarek,, T. Gootz,,and N. Osheroff. 2000. Action of quinolones againstStaphylococcus aureus topoisomerase IV; basis for DNAcleavage enhancement. Biochemistry 39:27262732.
6. Anderson, V. E.,, R. P. Zaniewski,, F. S. Kaczmarek,, T. D. Gootz,, and N. Osheroff. 1999. Quinolones inhibit DNAreligation mediated by Staphylococcus aureus topoisomeraseIV. J. Biol. Chem. 274:3592735932.
7. Ashizawa, Y.,, T. Yokochi,, Y. Ogata,, Y. Shobuike,, J . Kato,,and H. Ikeda. 1999. Mechanism of DNA gyrase-mediatedillegitimate recombination: characterization of Escherichiacoli gyrA mutants that confer hyper-recombination phenotype. J.Mol. Biol. 289:447458.
8. Bachellier, S.,, D. Perrin,, M. Hoffnung,, and E. Gilson. 1993.Bacterial interspersed mosaic elements (BIMEs) are presentin the genome of Klebsiella . Mol. Microbiol. 7:537544.
9. Bachellier, S.,, W. Saurin,, D. Perrin,, M. Homung,, and E. Gilson. 1994. Structural and functional diversity amongbacterial interspersed mosaic elements (BIMEs). Mol.Microbiol. 12:6170.
10. Bahng, S.,, E. Mossessova,, P. Nurse,, and K. Marians. 2000.Mutational analysis of Eshcerichia coli topoisomerase IV.J. Biol. Chem. 275:41124117.
11. Baird, C. L.,, T. T. Harkins,, S. K. Morris,, and J . E. Lindsley.1999. Topoisomerase II drives DNA transport by hydrolyzingone ATP. Proc. Natl. Acad. Sci. USA 96:1368513690.
12. Barnard, F.,, and A. Maxwell. 2001. Interaction betweenDNAgyrase and quinolones: the effect of alanine mutationsat A subunit residues Ser-83 andAsp-87. Antimicrob.Agents Chemother. 45:19942000.
13. Bendich, A. 2001. The form of DNA molecules in bacterialcells. Biochimie 83:177186.
14. Berardini, M.,, P. L. Foster,, and E. L. Loechler. 1999. DNApolymerase II (polB) is involved in a new DNA repair pathwayfor DNA interstrand cross-links in Escherichia coli . J.Bacteriol. 181:28782882.
15. Berger, J . M.,, S. J . Gamblin,, S. C. Harrison,, and J . C. Wang.1996. Structure and mechanism of DNA topoisomerase II.Nature 379:225232.
16. Blanche, F.,, B. Cameron,, F.-X. Bernard,, L. Maton,, B. Manse,, L. Ferrero,, N. Ratet,, C. Lecoq,, A. Goniot,, D. Bisch,,and J. Crouzet. 1996. Differential behaviors ofStaphylococcus aureus and Escherichia coli type II DNAtopoisomerases. Antimicrob. Agents Chemother. 40:27142720.
17. Boccard, F.,, and P. Prentki. 1993. Specific interaction of IHF with RIBs, a class of bacterial repetitive DNA elements located at the 39 end of transcription units. EMBO J.12:50195027.
18. Breines, D. M.,, S. Ouabdesselam,, E. Y. Ng,, J . Tankovic,, S. Shah,, C. J . Soussy,, and D. C. Hooper. 1997. Quinolone resistance locus nfxD of Escherichia coli is a mutant allele of the parE gene encoding a subunit of topoisomerase IV.Antimicrob. Agents Chemother. 41:175179.
19. Broccoli, S.,, P. Phoenix,, and M. Drolet. 2000. Isolation of the topB gene encoding DNA topoisomerase III as a multicopysuppressor of top A null mutations in Escherichia coli .Mol. Microbiol. 35:5868.
20. Burden, D. A.,, and N. Osheroff. 1999. In vitro evolution of preferred topoisomerase II DNA cleavage sites. J. Biol.Chem. 274:52275235.
21. Cambau, E.,, F. Borden,, E. Collatz,, and L. Gutmann. 1993.Novel gyrA point mutation in a strain of Escherichia coli resistant to fluoroquinolones but not to nalidixic acid.Antimicrob. Agents Chemother. 37:12471252.
22. Champoux, J . J . 2001. DNA topoisomerases: structure, function,and mechanism. Annu. Rev. Biochem. 70:369413.
23. Champoux, J .J ., , and M. D. Been,. 1980. Topoisomerasesand theswivel problem, p. 809815. In B. Alberts(ed.),Mechanistic Studies of DNA Replication and GeneticRecombination: ICN-UCLA Symposia onMolecular andCellular Biology. Academic Press, New York, N.Y.
24. Changela, A.,, R. DiGate,, and A. Mondragon. 2001. Crystalstructure of a complex of a type 1A DNA topoisomerasewith a single-stranded DNA molecule. Nature 411:10771081.
25. Chen, C.-R.,, M. Malik,, M. Snyder,, and K. Drlica. 1996.DNA gyrase and topoisomerase IV on the bacterial chromosome:quinolone-induced DNA cleavage. J . Mol. Biol. 258:627637.
26. Chow, R.,, T. Dougherty,, H. Fraimow,, E. Bellin,, and M. Miller. 1988. Association between early inhibition of DNAsynthesis and the MICs and MBCs of carboxyquinoloneantimicrobial agents for wild-type and mutant [gyrAnfxB(ompF) acrA] Escherichia coli K-12. Antimicrob.Agents Chemother. 32:11131118.
27. Cole, S. T.,, R. Brosch,, J . Parkhill,, T. Gamier,, C. Churcher,, D. Harris,, S. Gordon,, K. Eiglmeier,, S. Gas,, C. E. Barry,, F. Tekaia,, K. Babcock,, D. Basham,, D. Brown,, T. Chillingworth,, R. Connor,, R. Davies,, K. Devlin,, T. Feltwell,, S. Gentles,, N. Hamlin,, S. Holroyd,, T. Hornsby,, K. Jagels,,and B. Barrell. 1998. Deciphering the biology of Mycobacteriumtuberculosis from the complete genome sequence.Nature 393:537544.
28. Condemine, G.,, and C. Smith. 1990. Transcription regulatesoxolinic acid-induced DNA gyrase cleavage at specific sites onthe E. coli chromosome. Nucleic Acids Res. 18:73897395.
29. Cook, T. M.,, W. Deitz,, and W. Goss. 1966. Mechanism ofaction of nalidixic acid on Escherichia coli . J. Bacteriol.91:774779.
30. Crisona, N.,, T. Strick,, D. Bensimon,, V. Croquette,, and N. Cozzarelli. 2000. Preferential relaxation of positively supercoiledDNA by E. coli topoisomerase IV in single-moleculeand ensemble measurements. Genes Dev. 14:28812892.
31. Critchlow, S. E.,, and A. Maxwell. 1996. DNA cleavage isnot required for the binding of quinolone drugs to the DNAgyrase-DNA complex. Biochemistry 35:73877393.
32. Crumplin, G.,, M. Kenwright,, and T. Hirst. 1984.Investigations into the mechanism of action of the antibacterialagent norfloxacin.J. Antimicrob. Chemother. 13:923.
33. Crumplin, G. C.,, and J. T. Smith. 1975. Nalidixic acid: anantibacterial paradox. Antimicrob. Agents Chemother.8:251261.
34. Cullen, M.,, A. Wyke,, R. Kuroda,, and L. Fisher. 1989.Cloning and characterization of a DNA gyrase A gene fromEscherichia coli that confers clinical resistance to 4-quinolones. Antimicrob. Agents Chemother. 33:886894.
35. Dasgupta, S.,, S. Maisnier-Patin,, and K. Nordstrom. 2000.New genes with old modus operandi . EMBO Rep.1:323327.
36. Dean, F.,, M. Krasnow,, R. Otter,, M. Matzuk,, S. Spengler,,and N. Cozzarelli. 1983. Escherichia coli type I topoisomerases:identification, mechanism and role in recombination.Cold Spring Harbor Symp. Quant. Biol. 47:769777.
37. Deitz, W.H.,, T. M. Cook,, and W. A. Goss. 1966. Mechanismof action of nalidixic acid on Escherichia coli. HI. Conditionsrequired for lethality. J .Bacteriol. 91:768773.
38. DiGate, R.,, and K. Marians. 1988. Identification of a potentdecatenating enzyme from Escherichia coli . J. Biol. Chem.263:1336613373.
39. DiGate, R.,, and K. Marians. 1989. Molecular cloning andDNA sequence analysis of Escherichia coli topB, the geneencoding topoisomerase Jr. J. Biol. Chem. 264:1792417930.
40. DiGate, R.,, and K. Marians. 1992. Escherichiacoli topoisomeraseIll-catalyzed cleavage of RNA. J. Biol. Chem.267:2053220535.
41. DiNardo, S.,, K. Voelkel,, R. Sternglanz,, A. Reynolds,, and A. Wright. 1982. Esherichia coli DNA topoisomerase Imutants have compensatory mutations in DNA gyrasegenes. Cell 31:4351.
42. Discotto, L. F.,, L. Lawrence,, K. Denbleyker,, and J . F. Barrett.2001. Staphylococcus aureus mutants selected by BMS-284756. Antimicrob. Agents Chemther. 45:32733275.
43. Dong, Y.,, C. Xu,, X. Zhao,, J . Domagala,, and K. Drlica.1998. Fluoroquinolone action against mycobacteria: effectsof C8 substituents on bacterial growth, survival, and resistance.Antimicrob. Agents Chemother. 42:29782984.
44. Dorman, C.,, G. Barr,, N. NiBhriain,, and C. Higgins. 1988.DNA supercoiling and the anaerobic growth phase regulationof tonB gene expression.J. Bacteriol. 170:28162826.
45. Drlica, K. 1992. Control of bacterial DNA supercoiling.Mol. Microbiol. 6:425433.
46. Drlica, K.,, R. Franco,, and T. Steck. 1988. Rifampicin andrpoB mutations can alter DNA supercoiling in Escherichiacoli . J. Bacteriol. 170:49834985.
47. Drlica, K.,, S. H. Manes,, and E. C. Engle. 1980. DNA gyraseon the bacterial chromosome: possibility of two levels ofaction. Proc. Natl. Acad. Sci. USA 77:68796883.
48. Drlica, K.,, and M. Snyder. 1978. Superhelical Escherichiacoli DNA: relaxation by coumermycin. J. Mol. Biol.120:145154.
49. Drlica, K.,, and X . Zhao. 1997. DNA gyrase, topoisomeraseIV, and the 4-quinolones. Microbiol. Mol. Biol. Rev.61:377392.
50. Drolet, M.,, P. Phoenix,, R. Menzel,, E. Masse,, L. F. Liu, andR. J . Crouch. 1995. Overexpression of RNase H partiallycomplements the growth defect of an Escherichia coli Atop A mutant: R-loop formation is a major problem in the absenceof DNA topoisomerase I. Proc. Natl. Acad. Sci. USA92:35263530.
51. Earnshaw, W. C.,, B. Halligan,, C. A. Cooke,, M. M. S. Heck,,and L. F. Liu. 1985. Topoisomerase II is a structural componentof mitotic chromosome scaffolds. J. Cell Biol.100:17061715.
52. Espeli, O.,, and F. Boccard. 1997. In vivo cleavage ofEscherichia coli BIME-2 repeats by DNA gyrase: geneticcharacterization of the target and identification of the cut site. Mol. Microbiol. 26:767777.
53. Fass, D.,, C. E. Bogden,, and J . M. Berger. 1999. Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands. Nat. Struct. Biol. 6:322326.
54. Ferrero, L.,, B. Cameron,, and J . Crouzet. 1995. Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin resistant mutants of Staphylococcus aureus . Antimicrob.Agents Chemother. 39:15541558.
55. Ferrero, L.,, B. Cameron,, B. Manse,, D. Lagneaux,, J . Crouzet,, A. Famechon,, and F. Blanche. 1994. Cloning and primary structure of Staphylococcus aureus DNA topoisomeraseIV: a primary target of fluoroquinolones. Mol.Microbiol. 13:641653.
56. Fisher, L. M.,, H. A. Barot,, and M. E. Cullen. 1986. DNAgyrase complex with DNA: determinants for site-specific DNA breakage. EMBO J. 5:14111418.
57. Fisher, L. M.,, K. Mizuuchi,, M. H. O'Dea,, H. Ohmori,, and M. Gellert. 1981. Site-specific interaction of DNA gyrase with DNA. Proc. Natl. Acad. Sci. USA 78:41654169.
58. Fournier, B.,, X . Zhao,, T. Lu,, K. Drlica,, and D. Hooper.2000. Selective targeting of topoisomerase IV and DNAgyrase in Staphylococcus aureus: different patterns of quinolone-induced inhibition of DNA synthesis. Antimicrob.Agents Chemother. 44:21602165.
59. Franco, R.,, and K. Drlica. 1988. DNA gyrase on the bacterial chromosome: oxolinic acid-induced DNA cleavage in the dnaA-gyrB region. J . Mol. Biol. 201:229233.
60. Fraser, C.,, S. Norris,, G. Weinstock,, O. White,, G. Sutton,, R. Dodson,, M. Gwinn,, E. Hickey,, R. Clayton,, K. Ketchum,, E. Sodergren,, J. Hardham,, M. McLeod,, S. Alzberg,, J. Peterson,, H. Khalak,, D. Richardson,, J. Howell,, M. Chidambaram,, T. Utterback,, L. McDonald,, P. Artiach,, C. Bowman,, M. Cotton,, C. Fujii,, S. Garland,, B. Hatch,, D. Horst,, K. Roberts,, M. Sandusky,, J. Weidman,, H. Smith,, and J. Venter. 1998.Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281:375388.
61. Friedman, S. M.,, T. Lu,, and K. Drlica. 2001. A mutation in the DNA gyrase A gene of Escherichia coli that expands the quinolone-resistance-determining region. Antimicrob.Agents Chemother. 45:23782380.
62. Fukuda, H.,, and K. Hiramatsu. 1999. Primary targets of fluoroquinolonesin Streptococcus pneumoniae . Antimicrob.Agents Chemother. 43:410412.
63. Fukuda, H.,, R. Kishi,, M. Takei,, and M. Hosaka. 2001.Contributions of the 8-methoxy group of gatifloxacin to resistance selectivity, target preference, and antibacterial activity against Streptococcus pneumoniae . Antimicrob.Agents Chemother. 45:16491653.
64. Gellert, M.,, M. H. O'Dea,, T. Itoh,, and J.-I. Tomizawa. 1976.Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase. Proc. Natl. Acad. Sci. USA73:44744478.
65. Gellert, M.,, M. H. O'Dea,, K. Mizuuchi,, and H. Nash. 1976.DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc. Natl. Acad. Sci. USA 73:38723876.
66. Gmuender, H.,, K. Kuratli,, K. DiPadova,, C. P. Gray,, W. Keck,, and S. Evers. 2001. Gene expression changes triggered by exposure of Haemophilus influenzae to novobiocin orciprofloxacin: combined transcription and translation analysis.Genome Res. 11:2842.
67. Goldman, J . D.,, D. G. White,, and S. V. Levy. 1996. Multipleantibiotic resistance (mar) locus protects Escherichia coli from rapid cell killing by fluoroquinolones. Antimicrob.Agents Chemother. 40:12661269.
68. Goldstein, E.,, and K. Drlica. 1984. Regulation of bacterialDNA supercoiling: plasmid linking number varies with growth temperature. Proc. Natl. Acad. Sci. USA 81:40464050.
69. Gootz, T. D. 2001. Bactericidal assays for fluoroquinolones. Methods Mol. Biol. 95:185194.
70. Gootz, T. D.,, R. P. Zaniewski,, S. L. Haskell,, F. S. Kaczmarek,, and A.E. Maurice. 1999. Activities oftrovafloxacin compared with those of other fluoroquinolones against purified topoisomerases and gyrA and grlA mutants of Staphylococcus aureus . Antimicrob. Agents Chemother. 43:18451855.
71. Goss, W.,, W. Deitz,, and T. Cook. 1964. Mechanism ofaction of nalidixic acid on Escherichia coli . J. Bacteriol.88:11121118.
72. Goss, W.,, W. Deitz,, and T. Cook. 1965. Mechanism ofaction of nalidixic acid on Escherichia coli. II. Inhibition of deoxyribonucleic acid synthesis. J. Bacteriol. 89:0681074.
73. Gradelski, E.,, B. Kolek,, D. Bonner,, L. Valera,, B. Minassian,,and J . Fung-Tome. 2001. Activity of gatifloxacin and ciprofloxacin in combination with other antimicrobial agents. Int. J. Antimicrob. Agents 17:103107.
74. Green, M.,, J . Donch,, and J . Greenburg. 1970. Effect of inhibitors of DNA synthesis on UV-sensitive derivatives ofEscherichia coli strain K-12. Mutat. Res. 9:149154.
75. Guillemin, I.,, V. Jarlier,, and E. Cambau. 1998. Correlation between quinolone sensitivity patterns and sequences in the A and B subunits of DNA gyrase in mycobacteria.Antimicrob. Agents Chemother. 42:20842088.
76. Guillemin, I.,, W. Sougakoff,, E. Cambau,, V. Revel-Viravau,, N. Moreau,, and V. Jarlier. 1999. Purification and inhibition by quinolones of DNA gyrases from Mycobacterium avium,Mycobacterium smegmatis and Mycobacterium fortuitum by. peregrinum. Microbiology 145:25272532.
77. Hallett, P.,, and A. Maxwell. 1991. Novel quinolone resistance mutations of the Escherichia coli DNA gyrase A protein; enzymaticanalysis of the mutant proteins. Antimicrob.Agents Chemother. 35:335340.
78. Hanafi, D.,, and L. Bossi. 2000. Activation and silencing of leu-500 promter by transcription-induced DNA supercoiling in the Salmonella chromosome. Mol. Microbiol. 37:583594.
79. Harmon, F.,, R. DiGate,, and S. Kowaiczykowski. 1999.RecQ helicases adn topoisomerase III comprise a novel DNA strand passage function: a conserved mechanism for control of DNA recombination. Mol. Cell 3:611ndash;620.
80. Heaton, V. J.,, J. E. Ambler,, and L. M. Fisher. 2000. Potentantipneumococcal activity of gemifloxacin is associated with dual targeting of gyrase and topoisomerase IV, an in vivo target preference for gyrase, and enhanced stabilization of cleavable complexes invitro. Antimicrob. AgentsChemother. 44:31123117.
81. Hecht, R. M.,, and D. E. Pettijohn. 1976. Studies of DNA bound RNA molecules isolated from nucleoids of Escherichia coli . Nucleic Acids Res. 3:767788.
82. Heddle, J .,, T. Lu,, X. Zhao,, K. Drlica, and A. Maxwell.2001. gyrB-225, a mutation of DNA gyrase that compensates for topoisomerase I deficiency: investigation of its low activity and quinolone hypersensitivity. J. Mol. Biol.309:12191231.
83. Heddle, J . G.,, F. Barnard,, L. Wentzell,, and A. Maxwell.2000. The interaction of drugs with DNA gyrase: a model for the molecular basis of quinolone action. Nucleosides Nucleotides Nucleic Acids 19:12491264.
84. Hiasa, H. K.,, and J. Marians. 1996. Two distinct modes of strand unlinking during theta-type DNA replication. J . Biol.Chem. 271:2152921535.
85. Hiasa, H.,, D. Yousef,, and K. Marians. 1996. DNA strand cleavage is required for replication fork arrest by a frozen topoisomerase-quinolone-DNA ternary complex. J. Biol.Chem. 271:2642426429.
86. Higgins, C. F.,, C. J . Dorman,, D. A. Stirling,, L. Waddell,, I.R. Booth,, G. May,, and E. Bremer. 1988. A physiological role for DNA supercoiling in the osmotic regulation of gene expression in S. typhimurium and E. coli . Cell 52:569584.
87. Holmes, V.,, and N. Cozzarelli. 2000. Closing the ring: links between SMC proteins and chromosome partitioning, condensation, and supercoiling. Proc. Natl. Acad. Sci. USA97:13221324.
88. Hong, G.,, and K. Kreuzer. 2000. An antitumor drug induced topoisomerase cleavage complex blocks a bacteriophageT4 replication fork in vivo. Mol. Cell. Biol. 20:594603.
89. Hsieh, L.-S.,, R. M. Burger,, and K. Drlica. 1991. Bacterial DNA supercoiling and [ATP]/[ADP]: Changes associated with a transition to anaerobic growth. J. Mol. Biol.219:443450.
90. Hsieh, L.-S.,, J . Rouviere-Yaniv,, and K. Drlica. 1991.Bacterial DNA supercoiling and [ATP]/[ADP]: Changes associated with salt shock. J. Bacteriol. 173:39143917.
91. Huang, W. M.,, J . Libbey,, P. VanderHoeven,, and S. X. Yu.1998. Bipolar localization of Bacillus subtilis topoisomeraseIV, an enzyme required for chromosome segregation. Proc.Natl. Acad. Sci. USA 95:46524657.
92. Ikeda, H. 1994. DNA topoisomerase-mediated illegitimate recombination. Adv. Pharmacol. 29A:147165.
93. Ince, D.,, and D. Hooper. 2000. Mechanisms and frequency of resistance to premafloxacin in Staphylococcus aureus: Novel mutations suggest novel drug-target interactions. Antimicrob. Agents Chemother. 44:33443350.
94. Ince, D.,, and D. C. Hooper. 2001. Mechanisms and frequency of resistance to gatifloxacin in comparison to AM-1121 and ciprofloxacin in Staphylococcus aureus. Antimicrob.Agents Chemother. 45:27552764.
95. Kampranis, S.,, and A. Maxwell. 1998. Conformational changes in DNA gyrase revealed by limited proteolysis. J. Biol. Chem. 273:2260622614.
96. Kampranis, S.,, and A. Maxwell. 1998. The DNA gyrase quinolone complex, ATP hydrolysis and the mechanism of DNA cleavage.J. Biol. Chem. 273:2261522626.
97. Kampranis, S.,, and A. Maxwell. 1998. Hydrolysis of ATP at only one GyrB subunit is sufficient to promote super coiling by DNA gyrase. J . Biol. Chem. 273:2630525309.
98. Kampranis, S. C.,, and A. Maxwell. 1996. Conversion of DNA gyrase into a conventional type II topoisomerase. Proc.Natl. Acad. Sci. USA 93:1441614421.
99. Kato, J.-L.,, Y. Nishimura,, R. Imamura,, H. Niki,, S. Hiraga,, and H. Suzuki. 1990. New topoisomerase essential for chromosome segregation in E. coli . Cell 63:393404.
100. Khodursky, A.,, and N. Cozzarelli. 1998. The mechanism of inhibition of topoisomerase IV by quinolone antibacterials.J. Biol. Chem. 273:2766827677.
101. Khodursky, A.,, B. Peter,, M. Schmid,, J . DeRisi,, D. Botstein,, P. Brown,, and N. Cozzarelli. 2000. Analysis of topoisomerase function in bacterial replication fork movement: use of DNA microarrays. Proc. Natl. Acad. Sci. USA97:94199424.
102. Khodursky, A. B.,, E. L. Zechiedrich,, and N. R. Cozzarelli.1995. Topoisomerase IV is a target of quinolones in Escherichia coli . Proc. Natl. Acad. Sci. USA 92:1180111805.
103. Krasin, F.,, and F. Hutchinson. 1977. Repair of DNA double strand breaks in Escherichia coli, which requires recA function and the presence of a duplicate genome. J. Mol. Biol.116:8198.
104. Levine, C.,, H. Hiasa,, and K. Marians. 1998. DNA gyrase and topoisomerase IV: Biochemical activities, physiological roles during chromosome replication, and drug sensitivities.Biochim. Biophys. Acta 1400:2943.
105. Lewin, C.,, B. Howard,, N. Ratcliffe,, and J. Smith. 1989. 4-Quinolones and the SOS response. J. Med. Microbiol.29:139144.
106. Lewin, C.,, and J. Smith. 1990. DNA breakdown by the 4-quinolones and its significance.J. Med. Microbiol. 31:6570.
107. Li, X.,, X. Zhao,, and K. Drlica. 2002. Selection of Streptococcus pneumoniae mutants having reduced susceptibility to levofloxacin and moxifloxacin. Antimicrob. AgentsChemother. 46:522524.
108. Lima, C.,, J. C. Wang,, and A. Mondragon. 1994. Three dimensional structure of the 67K N-terminal fragment of E.coli DNA topoisomerase I. Nature 367:138146. 109.
109. Liu, L.,, and J . Wang. 1987. Supercoiling of the DNA template during transcription. Proc. Natl. Acad. Sci. USA 84:70247027.
110. Lockshon, D.,, and D. R. Morris. 1985. Sites of reaction ofEscherichia coli DNA gyrase on pBR322 in vivo as revealed by oxolinic acid-induced plasmid linearization. J . Mol. Biol.181:6374.
111. Lu, T.,, X. Zhao,, and K. Drlica. 1999. Gatifloxacin activity against quinolone-resistant gyrase: allele-specific enhancement of bacteriostatic and bactericidal activity by the C-8-methoxygroup. Antimicrob. Agents Chemother. 43:29692974.
112. Manes, S. H.,, G. J . Pruss,, and K. Drlica. 1983. Inhibition of RNA synthesis by oxolinic acid is unrelated to average DNA supercoiling. J. Bacteriol. 155:420423.
113. Mao, Y .,, M. Sun,, S. Desai,, and L. Liu. 2000. SUMO-1 conjugation to topoisomerase I: a possible repair response to topoisomerase-mediated DNA damage. Proc. Natl. Acad.Sci. USA 97:40464051.
114. Marians, K.,, and H. Hiasa. 1997. Mechanism of quinolone action: a drug-induced structural perturbation of the DNA precedes strand cleavage by topoisomerase IV. J . Biol.Chem. 272:94019409.
115. Marshall, D.,, F. Bowe,, C. Hale,, G. Dougan,, and C. Dorman.2000. DNA topology and adaptation of Salmonellatyphimurium to an intracellular environment. Philos. Trans.R. Soc. Lond. 355:565574.
116. McDaniel, L. S.,, L. H. Rogers,, and W. E. Hill. 1978.Survival of recombination-deficient mutants of Escherichiacoli during incubation with nalidixic acid. J . Bacteriol.134:11951198.
117. McEachem, F.,, and L. M. Fisher. 1989. Regulation of DNA supercoiling in Escherichia coli: genetic basis of a compensatory mutation in DNA gyrase. FEBS Lett. 253:6770.
118. McNairn, E.,, N. N. Bhriain,, and C. Dorman. 1995.Overexpression of the Shigella flexneri genes coding for DNA topoisomerase IV compensates for loss of DNA topoisomerase I: effect on virulence gene expression. Mol.Microbiol. 15:507517.
119. Menzel, R.,, and M. Gellert. 1983. Regulation of the genes for E. coli DNA gyrase: homeostatic control of DNA supercoiling. Cell 34:105113.
120. Mizushima, T.,, Y. Ohtsuka,, T. Miki,, and K. Sekimizu.1994. Temperature shift-up leads to simultaneous and continuous plasmid DNA relaxation and induction of DnaK and GroEL proteins in anaerobically growing Escherichiacoli cells. FEMS Microbiol. Lett. 121:333336.
121. Mondragon, A.,, and R. DiGate. 1999. The structure of the Escherichia coli DNA topoisomerase III. Structure (Lond.)7:13731383.
122. MoraisCabral, J . H.,, A. P. Jackson,, C. V. Smith,, N. Shikotra,, A. Maxwell,, and R. C. Liddington. 1997. Crystalstructure of the breakage-reunion domain of DNA gyrase. Nature 388:903906.
123. Moreau, N. J .,, H. Robaux,, L. Baron,, and X. Tabary. 1990. Inhibitory effects of quinolones on pro- and eukaryotic DNA topoisomerases I and II. Antimicrob. AgentsChemother. 34:19551960.
124. Morris, J .,, X.-S. Pan,, and L. M. Fisher. 2002.Grepafloxacin, a dimethyl derivative of ciprofloxacin, acts preferentially through gyrase in Streptococcus pneumoniae: role of the C-5 group in target specificity. Antimicrob.Agents Chemother. 46:582585.
125. Morrison, A.,, and N. R. Cozzarelli. 1979. Site-specific cleavage of DNA by E. coli DNA gyrase. Cell 17:175184.
126. Morrissey, L.,, and J. George. 1999. Activities of fluoroquinolones against Streptococcus pneumoniae type II topoisomerases purified as recombinant proteins. Antimicrob.Agents Chemother. 43:25702585.
127. Morrissey, I.,, and J. George. 2000. Bactericial activity of gemifloxacin and other quinolones against Streptococcuspneumoniae . J. Antimicrob. Chemother. 45(Suppl. SI):107110.
128. Ng, E. Y.,, M. Trucksis,, and D. C. Hooper. 1996. Quinolone resistance mutations in topoisomerase IV: relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus . Antimicrob.Agents Chemother. 40:18811888.
129. O'Connor, M. B.,, and M. H. Malamy. 1985. Mapping of DNA gyrase cleavage sites in vivo. Oxolinic acid induced cleavages in plasmid pBR322. J . Mol. Biol. 181:545550.
130. Onodera, Y.,, Y. Uchida,, M. Tanaka,, and K. Sato. 1999.Dual inhibitory activity of sitafloxacin (DU-6859a) against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae .J. Antimicrob. Chemother. 44:533536.
131. Oram, M.,, and M. Fisher. 1991. 4-quinolone resistance mutations in the DNA gyrase of Escherichia coli clinical isolates identified by using the polymerase chain reaction. Antimicrob. Agents Chemother. 35:387389.
132. Pan, X .,, and L. M. Fisher. 1997. Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones. Antimicrob. Agents Chemother. 41:471474.
133. Pan, X .,, and L. M. Fisher. 1998. DNA gyrase and topoisomeraseIV are dual targets of clinafloxacin action in Streptococcus pneumoniae . Antimicrob. Agents Chemother.42:28102816.
134. Pan, X.-S.,, J . Ambler,, S. Mehtar,, and L. M. Fisher. 1996.Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae . Antimicrob. Agents Chemother. 40:23212326.
135. Pan, X.-S.,, and L. M. Fisher. 1999. Streptococcus pneumoniae DNA gyrase and topoisomerase IV: overexpression, purification, and differential inhibition by fluoroquinolones. Antimicrob. Agents Chemother. 43:11291136.
136. Pan, X.-S.,, G. Yague,, and L. M. Fisher. 2001. 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. AgentsChemother. 45:31403147.
137. Pato, M. L.,, M. Karlock,, C. Wall,, and N. P. Higgins. 1995.Characterization of Mu prophage lacking the central strong gyrase binding site: localization of the block in replication. J. Bacteriol. 177:59375942.
138. Pestova, E.,, R. Beyer,, N. P. Cianciotto,, G. A. Noskin,, and L.R. Peterson. 1999. Contribution of topoisomerase IV andDNA gyrase mutations in Streptococcus pneumoniae to resistance to novel fluoroquinolones. Antimicrob. AgentsChemother. 43:20002004.
139. Pestova, E.,, J . Millichap,, G. Noskin,, and L. Peterson. 2000.Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. J. Antimicrob. Chemother. 45:583590.
140. Piddock, L.,, and R. Walters. 1992. Bactericidal activities of five quinolones for Escherichia coli strains with mutations in genes encoding the SOS response or cell division. Antimicrob.Agents Chemother. 36:819825.
141. Postow, L.,, N. Crisona,, B. Peter,, C. Hardy,, and N. Cozzarelli. 2001. Topological challenges to DNA replication: conformations at the fork. Proc. Natl Acad. Sci. USA98:82198226.
142. Pouliot, J .,, K. Yao,, C. Robertson,, and H. Nash. 1999. Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes. Science 286:552555.
143. Pruss, G.,, and K. Drlica. 1986. Topoisomerase I mutants: the gene on pBR322 that encodes resistance to tetracycline affects plasmid DNA supercoiling. Proc. Natl. Acad. Sci.USA 83:89528956.
144. Pruss, G. J . 1985. DNA Topoisomerase I mutants: increased heterogeneity in linking number and other replicon-dependent changes in DNA supercoiling. J. Mol. Biol. 185:5163.
145. Pruss, G. J .,, S. H. Manes,, and K. Drlica. 1982. Escherichia coli DNA topoisomerase I mutants: increased supercoiling is corrected by mutations near gyrase genes. Cell 31:3542.
146. Ratcliffe, N. T.,, and J . T. Smith. 1984. Ciprofloxacin and ofloxacin exhibit a rifampicin-resistant bactericidal mechanism not detectable in other 4-quinolone antibacterial agents. J. Pharm. Pharmacol. 36:59P.
147. Reece, R.,, and A. Maxwell. 1991. DNA gyrase: structure and function. Crit. Rev. Biochem. Mol. Biol. 26:335375.
148. Sawitzke, J. A.,, and S. Austin. 2000. Suppression of chromosome segregation defects of Escherichia coli muk mutants by mutations in topoisomerase I. Proc. Natl. Acad. Sci. USA97:16711676.
149. Schofield, M. A.,, R. Agbunag,, M. Michaels,, and J . Miller.1992. Cloning and sequencing of Escherichia coli mutR shows its identity to topB, encoding topoisomerase III. J. Bacteriol. 1774:51685170.
150. Sindelar, G.,, X . Zhao,, A. Liew,, Y. Dong,, J . Zhou,, J. Domagala,,and K. Drlica. 2000. Mutant prevention concentration as a measure of fluoroquinolone potency against mycobacteria.Antimicrob. Agents Chemother. 44:33373343.
151. Sinden, R. R.,, J . O. Carlson,, and D. E. Pettijohn. 1980.Torsional tension in the DNA double helix measured with trimethylpsoralen in living E. coli cells. Cell 21:773783.
152. Smith, J . T.,, and C. S. Lewin,. 1988. Chemistry and mechanisms of action of the quinolone antibacterials, p. 2382. In V. T. Andriole (ed.), The Quinolones. Academic Press, San Diego, Calif..
153. Snyder, M.,, and K. Drlica. 1979. DNA gyrase on the bacterial chromosome: DNA cleavage induced by oxolinic acid. J. Mol. Biol. 131:287302.
154. Soussy, C.,, J. Wolfson,, E. Ng,, and D. Hooper. 1993.Limitations of plasmid complementation test for determination of quinolone resistance due to changes in gyrase A protein and identification of conditional quinolone resistance locus. Antimicrob. Agents Chemother. 37:25882592.
155. Sreedharan, S.,, M. Oram,, B. Jensen,, L. Peterson, and L,Fisher. 1990. DNA gyrase gyrA mutations in ciprofloxacin resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli . J.Bacteriol. 172:72607262.
156. Srivenugopal, K.,, D. Lockshon,, and D. Morris. 1984.Escherichia coli DNA topoisomerase III: purification and characterization of a new type I enzyme. Biochemistry 23:18991906.
157. Staczek, P.,, and N. P. Higgins. 1998. Gyrase and topo IVmodulate chromosome domain size in vivo . Mol. Microbiol.29:14351448.
158. Steck, T. R.,, and K. Drlica. 1984. Bacterial chromosome segregation: evidence for DNA gyrase involvement in decatenation.Cell 36:10811088.
159. Steck, T. R.,, G. J . Pruss,, S. H. Manes,, L. Burg,, and K. Drlica. 1984. DNA supercoiling in gyrase mutants. J. Bacteriol. 158:397403.
160. Tabary, X .,, N. Moreau,, C. Dureuil,, and F. LeGoffic. 1987. Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and chlorobiocin on Escherichiacoli topoisomerase I. Antimicrob. Agents Chemother. 31:19251928.
161. Tomb, J .,, O. White,, A. Kerlavage,, R. Clayton,, G. Sutton,, R. Fleischmann,, K. Ketchum,, H. Klenk,, S. Gill,, B. Dougherty,, K. Nelson,, J. Quackenbush,, L. Zhou,, E. Kirkness,, S. Peterson,, B. Loftus,, D. Richardson,, R. Dodson,, H. Khalak,, A. Glodek,, K. McKenney,, L. Fitzegerald,, N. Lee,, M. Adams,, and J. Venter. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori . Nature 388:539547.
162. Tse-Dinh, Y. 2000. Increased sensitivity to oxidative challenges associated with top A deletion in Escherichia coli . J.Bacteriol. 182:829832.
163. Tse-Dinh, Y.-C. 1985. Regulation of the Eschericia coli DNA topoisomerase I gene by DNA supercoiling. Nucleic Acids Res. 13:47514763.
164. Tse-Dinh, Y.-C.,, H. Qi,, and R. Menzel. 1997. DNA supercoiling and bacterial adaptation: thermotolerance and thermoresistance.Trends Microbiol. 5:323326.
165. Wang, J.-Y.,, and M. Syvanen. 1992. DNA twist as a transcriptional sensor for environmental changes. Mol.Microbiol. 6:18611866.
166. Wang, J . C. 1971. Interaction between DNA and an Escherichia coli protein. J . Mol. Biol. 55:523533.
167. Wang, J . C. 1998. Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine. Q. Rev. Biophys. 31:107144.
168. Weinstein-Fischer, D.,, M. Elgrably-Weiss,, and S. Altuvia,2000. Escherichia coli response to hydrogen peroxide: a role for DNA supercoiling, topoisomerase I, and Fis. Mol.Microbiol. 35:14131420.
169. Wentzell, L.,, and A. Maxwell. 2000. The complex of DNAgyrase and quinolone drugs on DNA forms a barrier to theT7 DNA polymerase replication complex. J. Mol. Biol.304:779791.
170. Whoriskey, S.,, M. Scholfield,, and J . Miller. 1991. Isolation and characterization of Escherichia coli mutants with altered rates of deletion formation. Genetics 127:2130.
171. Wigley, D. B.,, G. J . Davies,, E. J . Dodson,, A. Maxwell,, and D. Dodson. 1991. Crystal structure of an N-terminal fragment of the DNA gyrase B protein. Nature 351:624629.
172. Williams, N.,, A. Howells,, and A. Maxwell. 2001. Locking the ATP-operated clamp of DNA gyrase: probing the mechanism of strand passage. J. Mol. Biol. 306:969984.
173. Williams, N. L.,, and A. Maxwell. 1999. Locking the DNA gate of DNA gyrase: investigating the effects on DNA cleavage and ATP hydrolysis. Biochemistry 38:1415714164.
174. Willmott, C. J . R.,, S. E. Critchlow,, I. C. Eperon,, and A. Maxwell. 1994. The complex of DNA gyrase and quinolone drugs with DNA forms a barrier to transcription by RNApolymerase. J. Mol. Biol. 242:351363.
175. Willmott, C. J . R.,, and A. Maxwell. 1993. A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex.Antimicrob. Agents Chemother. 37:126127.
176. Wolfson, J . S.,, D. C. Hooper,, D. J . Shih,, G. L. McHugh,, and M. N. Swartz. 1989. Isolation and characterization of an Escherichia coli strain exhibiting partial tolerance to quinolones. Antimicrob. Agents Chemother. 33:705709.
177. Wu, H.-Y.,, S.-H. Shyy,, J . C. Wang,, and L. F. Liu. 1988.Transcription generates positively and negatively supercoiled domains in the template. Cell 53:433440.
178. Wu, L.,, and I. Hickson. 2001. RecQ helicases and topoisomerases:components of a conserved complex for the regulationof genetic recombination. CMLS Cell. Mol. Life Sci.58:894901.
179. Yague, G.,, J . Morris,, X.-S. Pan,, K. Gould,, and L. M. Fisher.2002. Cleavable-complex formation by wild-type and quinolone-resistant Streptococcus pneumoniae type II topoisomerases mediated by gemifloxacin and other fluoroquinolones. Antimicrob. Agents Chemother. 46:413419.
180. Yang, S.-W.,, A. B. Burgin,, B. N. Huizenga,, C. A. Robertson,, K. C. Yao,, and H. A. Nash. 1996. A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases. Proc. Natl. Acad.Sci. USA 93:1153411539.
181. Yang, Y .,, and G. Ames. 1988. DNA gyrase binds to the family of prokaryotic repetitive extragenic palindromicsequences. Proc. Natl. Acad. Sci. USA 85:88508854.
182. Yang, Y .,, and G. Ames,. 1990. The family of repetitive extragenic palindromic sequences: interaction with DNA gyrase and histonelike protein HU, p. 211225. In K. Drlica, and M. Riley (ed.), The Bacterial Chromosome. American Society for Microbiology, Washington, D.C..
183. Yoshida, H.,, M. Bogaki,, M. Nakamura,, and S. Nakamura.1990. Quinolone resistance-determining region in the DNAgyrase gyrA gene of Escherichia coli . Antimicrob. AgentsChemother. 34:12711272.
184. Yoshida, H.,, M. Bogaki,, M. Nakamura,, L. Yamanaka,, and S. Nakamura. 1991. Quinolone resistance-determining region in the DNA gyrase gyrB gene of Escherichia coli . Antimicrob. Agents Chemother. 35:16471650.
185. Yoshida, H.,, M. Nakamura,, M. Bogaki,, H. Ito,, T. Kojima,, H. Hattori,, and S. Nakamura. 1993. Mechanism of action of quinolones against Escherichia coli DNA gyrase. Antimicrob. Agents Chemother. 37:839845.
186. Zechiedrich, E. L.,, A. Khodursky,, S. Bachellier,, R. Schneider,, D. Chen,, D. Lilley,, and N. Cozzarelli. 2000. Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli . J. Biol. Chem. 275:81038113.
187. Zhao, B.-Y.,, R. Pine,, J . Domagala,, and K. Drlica. 1999.Fluoroquinolone action against clinical isolates of Mycobacterium tuberculosis: effects of a C8-methoxyl group on survival in liquid media and in human macrophages. Antimicrob. Agents Chemother. 43:661666.
188. Zhao, X.,, J.-Y. Wang,, C. Xu,, Y. Dong,, J . Zhou,, J . Domagala,, and K. Drlica. 1998. Killing of Staphylococcusaureus by C-8-methoxy fluoroquinolones. Antimicrob.Agents Chemother. 42:956958.
189. Zhao, X .,, C. Xu,, J. Domagala,, and K. Drlica. 1997. DNA topoisomerase targets of the fluoroquinolones: a strategy for avoiding bacterial resistance. Proc. Natl. Acad. Sci. USA 94:1399113996.
190. Zhu, Q.,, P. Pongpech,, and R. DiGate. 2001. Type I topoisomerase activity is required for proper chromosomal segregation in Escherichia coli . Proc. Natl. Acad. Sci. USA98:97669771.


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Table 1

Inhibition of purified topoisomerase activity by fluoroquinolones

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2
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Table 2

Primary fluoroquinolone targets defined genetically in

Citation: Drlica K, Hooper D. 2003. Mechanisms of Quinolone Action, p 19-40. In Hooper D, Rubinstein E (ed), Quinolone Antimicrobial Agents, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817817.ch2

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