This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fukuda, H.
Right arrow Articles by Hiramatsu, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fukuda, H.
Right arrow Articles by Hiramatsu, K.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 1999, p. 410-412, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Primary Targets of Fluoroquinolones in Streptococcus pneumoniae

Hideyuki Fukuda1,* and Keiichi Hiramatsu2

Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., 2399-1, Nogi, Shimotsuga, Tochigi 329-0114,1 and Department of Bacteriology, Juntendo University, 2-1-1, Hongo, Bunkyo, Tokyo 113-8421,2 Japan

Received 6 July 1998/Returned for modification 24 August 1998/Accepted 25 November 1998

Mutants of wild-type Streptococcus pneumoniae IID553 with mutations in parC were obtained by selection with trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin. All of the parC mutants were cross-resistant to the selecting agents but were not resistant to gatifloxacin and sparfloxacin. On the other hand, gyrA mutants were isolated by selection with gatifloxacin and sparfloxacin. The gyrA mutants were cross-resistant to gatifloxacin and sparfloxacin but were not resistant to the other fluoroquinolones tested. These results suggest that in wild-type S. pneumoniae the primary target of trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin is topoisomerase IV, whereas the primary target of gatifloxacin and sparfloxacin is DNA gyrase.

* Corresponding author. Mailing address: Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., 2399-1, Mitarai, Nogi, Shimotsuga, Tochigi, 329-0114 Japan. Phone: 81-280-56-2201. Fax: 81-280-57-1293. E-mail: fvbb0984{at}mb.infoweb.ne.jp.

Antimicrobial Agents and Chemotherapy, February 1999, p. 410-412, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Pan, X.-S., Gould, K. A., Fisher, L. M. (2009). Probing the Differential Interactions of Quinazolinedione PD 0305970 and Quinolones with Gyrase and Topoisomerase IV. Antimicrob. Agents Chemother. 53: 3822-3831 [Abstract] [Full Text]  
  • Cambau, E., Matrat, S., Pan, X.-S., Roth Dit Bettoni, R., Corbel, C., Aubry, A., Lascols, C., Driot, J.-Y., Fisher, L. M. (2009). Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. J Antimicrob Chemother 63: 443-450 [Abstract] [Full Text]  
  • Okumura, R., Hirata, T., Onodera, Y., Hoshino, K., Otani, T., Yamamoto, T. (2008). Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumoniae. J Antimicrob Chemother 62: 98-104 [Abstract] [Full Text]  
  • Huband, M. D., Cohen, M. A., Zurack, M., Hanna, D. L., Skerlos, L. A., Sulavik, M. C., Gibson, G. W., Gage, J. W., Ellsworth, E., Stier, M. A., Gracheck, S. J. (2007). In Vitro and In Vivo Activities of PD 0305970 and PD 0326448, New Bacterial Gyrase/Topoisomerase Inhibitors with Potent Antibacterial Activities versus Multidrug-Resistant Gram-Positive and Fastidious Organism Groups. Antimicrob. Agents Chemother. 51: 1191-1201 [Abstract] [Full Text]  
  • LaPlante, K. L., Rybak, M. J., Tsuji, B., Lodise, T. P., Kaatz, G. W. (2007). Fluoroquinolone Resistance in Streptococcus pneumoniae: Area Under the Concentration-Time Curve/MIC Ratio and Resistance Development with Gatifloxacin, Gemifloxacin, Levofloxacin, and Moxifloxacin. Antimicrob. Agents Chemother. 51: 1315-1320 [Abstract] [Full Text]  
  • Wang, Y. C., Lipsitch, M. (2006). Upgrading antibiotic use within a class: Tradeoff between resistance and treatment success. Proc. Natl. Acad. Sci. USA 103: 9655-9660 [Abstract] [Full Text]  
  • Leavis, H. L., Willems, R. J. L., Top, J., Bonten, M. J. M. (2006). High-Level Ciprofloxacin Resistance from Point Mutations in gyrA and parC Confined to Global Hospital-Adapted Clonal Lineage CC17 of Enterococcus faecium.. J. Clin. Microbiol. 44: 1059-1064 [Abstract] [Full Text]  
  • Davies, T. A., Yee, Y. C., Goldschmidt, R., Bush, K., Sahm, D. F., Evangelista, A. (2006). Infrequent occurrence of single mutations in topoisomerase IV and DNA gyrase genes among US levofloxacin-susceptible clinical isolates of Streptococcus pneumoniae from nine institutions (1999-2003). J Antimicrob Chemother 57: 437-442 [Abstract] [Full Text]  
  • Wickman, P. A., Moland, E. S., Black, J. A., Thomson, K. S. (2006). In Vitro Activity of DX-619, a Novel Des-Fluoro(6) Quinolone, against a Panel of Streptococcus pneumoniae Mutants with Characterized Resistance Mechanisms. Antimicrob. Agents Chemother. 50: 796-798 [Abstract] [Full Text]  
  • Strahilevitz, J., Hooper, D. C. (2005). Dual Targeting of Topoisomerase IV and Gyrase To Reduce Mutant Selection: Direct Testing of the Paradigm by Using WCK-1734, a New Fluoroquinolone, and Ciprofloxacin. Antimicrob. Agents Chemother. 49: 1949-1956 [Abstract] [Full Text]  
  • Sadowy, E., Izdebski, R., Skoczynska, A., Gniadkowski, M., Hryniewicz, W. (2005). High Genetic Diversity of Ciprofloxacin-Nonsusceptible Isolates of Streptococcus pneumoniae in Poland. Antimicrob. Agents Chemother. 49: 2126-2129 [Abstract] [Full Text]  
  • Yoo, B. K, Triller, D. M, Yong, C.-S., Lodise, T. P (2004). Gemifloxacin: A New Fluoroquinolone Approved for Treatment of Respiratory Infections. The Annals of Pharmacotherapy 38: 1226-1235 [Abstract] [Full Text]  
  • Schentag, J. J, Meagher, A. K, Forrest, A. (2003). Fluoroquinolone AUIC Break Points and the Link to Bacterial Killing Rates Part 2: Human Trials. The Annals of Pharmacotherapy 37: 1478-1488 [Abstract] [Full Text]  
  • Schentag, J. J, Meagher, A. K, Forrest, A. (2003). Fluoroquinolone AUIC Break Points and the Link to Bacterial Killing Rates: Part 1: In Vitro and Animal Models. The Annals of Pharmacotherapy 37: 1287-1298 [Abstract] [Full Text]  
  • Allen, G. P., Kaatz, G. W., Rybak, M. J. (2003). Activities of Mutant Prevention Concentration-Targeted Moxifloxacin and Levofloxacin against Streptococcus pneumoniae in an In Vitro Pharmacodynamic Model. Antimicrob. Agents Chemother. 47: 2606-2614 [Abstract] [Full Text]  
  • Johnson, C. N., Benjamin, W. H. Jr., Moser, S. A., Hollingshead, S. K., Zheng, X., Crain, M. J., Nahm, M. H., Waites, K. B. (2003). Genetic Relatedness of Levofloxacin-Nonsusceptible Streptococcus pneumoniae Isolates from North America. J. Clin. Microbiol. 41: 2458-2464 [Abstract] [Full Text]  
  • Griggs, D. J., Marona, H., Piddock, L. J. V. (2003). Selection of moxifloxacin-resistant Staphylococcus aureus compared with five other fluoroquinolones. J Antimicrob Chemother 51: 1403-1407 [Abstract] [Full Text]  
  • Kishii, R., Takei, M., Fukuda, H., Hayashi, K., Hosaka, M. (2003). Contribution of the 8-Methoxy Group to the Activity of Gatifloxacin against Type II Topoisomerases of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 47: 77-81 [Abstract] [Full Text]  
  • Ince, D., Zhang, X., Silver, L. C., Hooper, D. C. (2002). Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Garenoxacin (BMS-284756, T-3811ME), a New Desfluoroquinolone. Antimicrob. Agents Chemother. 46: 3370-3380 [Abstract] [Full Text]  
  • Jones, M. E., Karlowsky, J. A., Blosser-Middleton, R., Critchley, I. A., Karginova, E., Thornsberry, C., Sahm, D. F. (2002). Longitudinal Assessment of Antipneumococcal Susceptibility in the United States. Antimicrob. Agents Chemother. 46: 2651-2655 [Abstract] [Full Text]  
  • Houssaye, S., Gutmann, L., Varon, E. (2002). Topoisomerase Mutations Associated with In Vitro Selection of Resistance to Moxifloxacin in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46: 2712-2715 [Abstract] [Full Text]  
  • Jones, M. E., Critchley, I. A., Karlowsky, J. A., Blosser-Middleton, R. S., Schmitz, F.-J., Thornsberry, C., Sahm, D. F. (2002). In Vitro Activities of Novel Nonfluorinated Quinolones PGE 9262932 and PGE 9509924 against Clinical Isolates of Staphylococcus aureus and Streptococcus pneumoniae with Defined Mutations in DNA Gyrase and Topoisomerase IV. Antimicrob. Agents Chemother. 46: 1651-1657 [Abstract] [Full Text]  
  • Onodera, Y., Okuda, J., Tanaka, M., Sato, K. (2002). Inhibitory Activities of Quinolones against DNA Gyrase and Topoisomerase IV of Enterococcus faecalis. Antimicrob. Agents Chemother. 46: 1800-1804 [Abstract] [Full Text]  
  • Brueggemann, A. B., Coffman, S. L., Rhomberg, P., Huynh, H., Almer, L., Nilius, A., Flamm, R., Doern, G. V. (2002). Fluoroquinolone Resistance in Streptococcus pneumoniae in United States since 1994-1995. Antimicrob. Agents Chemother. 46: 680-688 [Abstract] [Full Text]  
  • Yague, G., Morris, J. E., Pan, X.-S., Gould, K. A., Fisher, L. M. (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: 413-419 [Abstract] [Full Text]  
  • Morris, J. E., Pan, X.-S., Fisher, L. M. (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: 582-585 [Abstract] [Full Text]  
  • Davies, T. A., Evangelista, A., Pfleger, S., Bush, K., Sahm, D. F., Goldschmidt, R. (2002). Prevalence of Single Mutations in Topoisomerase Type II Genes among Levofloxacin-Susceptible Clinical Strains of Streptococcus pneumoniae Isolated in the United States in 1992 to 1996 and 1999 to 2000. Antimicrob. Agents Chemother. 46: 119-124 [Abstract] [Full Text]  
  • Lawrence, L. E., Frosco, M., Ryan, B., Chaniewski, S., Yang, H., Hooper, D. C., Barrett, J. F. (2002). Bactericidal Activities of BMS-284756, a Novel Des-F(6)-Quinolone, against Staphylococcus aureus Strains with Topoisomerase Mutations. Antimicrob. Agents Chemother. 46: 191-195 [Abstract] [Full Text]  
  • Weigel, L. M., Anderson, G. J., Facklam, R. R., Tenover, F. C. (2001). Genetic Analyses of Mutations Contributing to Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 3517-3523 [Abstract] [Full Text]  
  • Takei, M., Fukuda, H., Kishii, R., Hosaka, M. (2001). Target Preference of 15 Quinolones against Staphylococcus aureus, Based on Antibacterial Activities and Target Inhibition. Antimicrob. Agents Chemother. 45: 3544-3547 [Abstract] [Full Text]  
  • Pan, X.-S., Yague, G., Fisher, L. M. (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. Agents Chemother. 45: 3140-3147 [Abstract] [Full Text]  
  • Ince, D., Hooper, D. C. (2001). Mechanisms and Frequency of Resistance to Gatifloxacin in Comparison to AM-1121 and Ciprofloxacin in Staphylococcus aureus. Antimicrob. Agents Chemother. 45: 2755-2764 [Abstract] [Full Text]  
  • Nagai, K., Davies, T. A., Dewasse, B. E., Jacobs, M. R., Appelbaum, P. C. (2001). Single- and multi-step resistance selection study of gemifloxacin compared with trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin in Streptococcus pneumoniae. J Antimicrob Chemother 48: 365-374 [Abstract] [Full Text]  
  • Thorburn, C. E., Edwards, D. I. (2001). The effect of pharmacokinetics on the bactericidal activity of ciprofloxacin and sparfloxacin against Streptococcus pneumoniae and the emergence of resistance. J Antimicrob Chemother 48: 15-22 [Abstract] [Full Text]  
  • Roychoudhury, S., Twinem, T. L., Makin, K. M., McIntosh, E. J., Ledoussal, B., Catrenich, C. E. (2001). Activity of non-fluorinated quinolones (NFQs) against quinolone-resistant Escherichia coli and Streptococcus pneumoniae. J Antimicrob Chemother 48: 29-36 [Abstract] [Full Text]  
  • Millichap, J. J., Pestova, E., Siddiqui, F., Noskin, G. A., Peterson, L. R. (2001). Fluoroquinolone Resistance Is a Poor Surrogate Marker for Type II Topoisomerase Mutations in Clinical Isolates of Streptococcus pneumoniae. J. Clin. Microbiol. 39: 2719-2721 [Abstract] [Full Text]  
  • Fukuda, H., Kishii, R., Takei, M., Hosaka, M. (2001). Contributions of the 8-Methoxy Group of Gatifloxacin to Resistance Selectivity, Target Preference, and Antibacterial Activity against Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 1649-1653 [Abstract] [Full Text]  
  • Richardson, D. C., Bast, D., McGeer, A., Low, D. E. (2001). Evaluation of Susceptibility Testing To Detect Fluoroquinolone Resistance Mechanisms in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 1911-1914 [Abstract] [Full Text]  
  • Klepser, M. E., Ernst, E. J., Petzold, C. R., Rhomberg, P., Doern, G. V. (2001). Comparative Bactericidal Activities of Ciprofloxacin, Clinafloxacin, Grepafloxacin, Levofloxacin, Moxifloxacin, and Trovafloxacin against Streptococcus pneumoniae in a Dynamic In Vitro Model. Antimicrob. Agents Chemother. 45: 673-678 [Abstract] [Full Text]  
  • Boos, M., Mayer, S., Fischer, A., Köhrer, K., Scheuring, S., Heisig, P., Verhoef, J., Fluit, A. C., Schmitz, F.-J. (2001). In Vitro Development of Resistance to Six Quinolones in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Antimicrob. Agents Chemother. 45: 938-942 [Abstract] [Full Text]  
  • Blondeau, J. M., Zhao, X., Hansen, G., Drlica, K. (2001). Mutant Prevention Concentrations of Fluoroquinolones for Clinical Isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 433-438 [Abstract] [Full Text]  
  • Khan, A. A., Slifer, T. R., Araujo, F. G., Remington, J. S. (2001). Activity of Gatifloxacin Alone or in Combination with Pyrimethamine or Gamma Interferon against Toxoplasma gondii. Antimicrob. Agents Chemother. 45: 48-51 [Abstract] [Full Text]  
  • Gmuender, H., Kuratli, K., Di Padova, K., Gray, C. P., Keck, W., Evers, S. (2001). Gene Expression Changes Triggered by Exposure of Haemophilus influenzae to Novobiocin or Ciprofloxacin: Combined Transcription and Translation Analysis. Genome Res 11: 28-42 [Abstract] [Full Text]  
  • Ince, D., Hooper, D. C. (2000). Mechanisms and Frequency of Resistance to Premafloxacin in Staphylococcus aureus: Novel Mutations Suggest Novel Drug-Target Interactions. Antimicrob. Agents Chemother. 44: 3344-3350 [Abstract] [Full Text]  
  • Bast, D. J., Low, D. E., Duncan, C. L., Kilburn, L., Mandell, L. A., Davidson, R. J., de Azavedo, J. C. S. (2000). Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae: Contributions of Type II Topoisomerase Mutations and Efflux to Levels of Resistance. Antimicrob. Agents Chemother. 44: 3049-3054 [Abstract] [Full Text]  
  • Heaton, V. J., Ambler, J. E., Fisher, L. M. (2000). Potent Antipneumococcal 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 In Vitro. Antimicrob. Agents Chemother. 44: 3112-3117 [Abstract] [Full Text]  
  • Poole, K. (2000). Efflux-Mediated Resistance to Fluoroquinolones in Gram-Positive Bacteria and the Mycobacteria. Antimicrob. Agents Chemother. 44: 2595-2599 [Full Text]  
  • Bébéar, C. M., Grau, O., Charron, A., Renaudin, H., Gruson, D., Bébéar, C. (2000). Cloning and Nucleotide Sequence of the DNA Gyrase (gyrA) Gene from Mycoplasma hominis and Characterization of Quinolone-Resistant Mutants Selected In Vitro with Trovafloxacin. Antimicrob. Agents Chemother. 44: 2719-2727 [Abstract] [Full Text]  
  • Nagai, K., Davies, T. A., Pankuch, G. A., Dewasse, B. E., Jacobs, M. R., Appelbaum, P. C. (2000). In Vitro Selection of Resistance to Clinafloxacin, Ciprofloxacin, and Trovafloxacin in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44: 2740-2746 [Abstract] [Full Text]  
  • Fournier, B., Zhao, X., Lu, T., Drlica, K., Hooper, D. C. (2000). Selective Targeting of Topoisomerase IV and DNA Gyrase in Staphylococcus aureus: Different Patterns of Quinolone- Induced Inhibition of DNA Synthesis. Antimicrob. Agents Chemother. 44: 2160-2165 [Abstract] [Full Text]  
  • Marchese, A., Debbia, E. A., Schito, G. C. (2000). Comparative in vitro potency of gemifloxacin against European respiratory tract pathogens isolated in the Alexander Project. J Antimicrob Chemother 46: 11-15 [Abstract] [Full Text]  
  • Pestova, E., Millichap, J. J., Noskin, G. A., Peterson, L. R. (2000). Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. J Antimicrob Chemother 45: 583-590 [Abstract] [Full Text]  
  • Alovero, F. L., Pan, X.-S., Morris, J. E., Manzo, R. H., Fisher, L. M. (2000). Engineering the Specificity of Antibacterial Fluoroquinolones: Benzenesulfonamide Modifications at C-7 of Ciprofloxacin Change Its Primary Target in Streptococcus pneumoniae from Topoisomerase IV to Gyrase. Antimicrob. Agents Chemother. 44: 320-325 [Abstract] [Full Text]  
  • Brisse, S., Fluit, A. C., Wagner, U., Heisig, P., Milatovic, D., Verhoef, J., Scheuring, S., Köhrer, K., Schmitz, F.-J. (1999). Association of Alterations in ParC and GyrA Proteins with Resistance of Clinical Isolates of Enterococcus faecium to Nine Different Fluoroquinolones. Antimicrob. Agents Chemother. 43: 2513-2516 [Abstract] [Full Text]  
  • Gootz, T. D., Zaniewski, R. P., Haskell, S. L., Kaczmarek, F. S., Maurice, A. E. (1999). Activities of Trovafloxacin Compared with Those of Other Fluoroquinolones against Purified Topoisomerases and gyrA and grlA Mutants of Staphylococcus aureus. Antimicrob. Agents Chemother. 43: 1845-1855 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»