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 Pestova, E.
Right arrow Articles by Peterson, L. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pestova, E.
Right arrow Articles by Peterson, L. R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 1999, p. 2000-2004, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Contribution of Topoisomerase IV and DNA Gyrase Mutations in Streptococcus pneumoniae to Resistance to Novel Fluoroquinolones

Ekaterina Pestova,1,* Rebecca Beyer,1 Nicholas P. Cianciotto,2 Gary A. Noskin,1,3 and Lance R. Peterson1,3

Department of Pathology,1 Department of Microbiology,2 and Department of Medicine,3 Northwestern University Medical School, Chicago, Illinois 60611

Received 16 December 1998/Returned for modification 3 March 1999/Accepted 9 June 1999

In this study, we assessed the activity of ciprofloxacin, levofloxacin, sparfloxacin, and trovafloxacin against clinical isolates of Streptococcus pneumoniae that were resistant to the less-recently developed fluoroquinolones by using defined amino acid substitutions in DNA gyrase and topoisomerase IV. The molecular basis for resistance was assessed by using mutants selected with trovafloxacin, ciprofloxacin, and levofloxacin in vitro. This demonstrated that the primary target of trovafloxacin in S. pneumoniae is the ParC subunit of DNA topoisomerase IV, similar to most other fluoroquinolones. However, first-step mutants bearing the Ser79right-arrowPhe/Tyr substitution in topoisomerase IV subunit ParC were susceptible to trovafloxacin with a minimum inhibitory concentration of 0.25 µg/ml, and mutations in the structural genes for both topoisomerase IV subunit ParC (parC) and the DNA gyrase subunit (gyrA) were required to achieve levels of resistance above the breakpoint. The data also suggest that enhanced activity of trovafloxacin against pneumococci is due to a combination of factors that may include reduced efflux of this agent and an enhanced activity against both DNA gyrase and topoisomerase IV.

* Corresponding author. Mailing address: Department of Pathology, Ward Building, 6-223, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-8188. Fax: (312) 908-4137. E-mail: evp606{at}anima.nums.nwu.edu.

Antimicrobial Agents and Chemotherapy, August 1999, p. 2000-2004, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • De Vecchi, E., Nicola, L., Ossola, F., Drago, L. (2009). In vitro selection of resistance in Streptococcus pneumoniae at in vivo fluoroquinolone concentrations. J Antimicrob Chemother 63: 721-727 [Abstract] [Full Text]  
  • Starr, J. A., Fox, G. W., Clayton, J. K. (2008). Streptococcus pneumoniae: An Update on Resistance Patterns in the United States. Journal of Pharmacy Practice 21: 363-370 [Abstract]  
  • Touyama, M., Higa, F., Nakasone, C., Shinzato, T., Akamine, M., Haranaga, S., Tateyama, M., Nakasone, I., Yamane, N., Fujita, J. (2006). In vitro activity of sitafloxacin against clinical strains of Streptococcus pneumoniae with defined amino acid substitutions in QRDRs of gyrase A and topoisomerase IV. J Antimicrob Chemother 58: 1279-1282 [Abstract] [Full Text]  
  • Decousser, J.-W., Methlouthi, I., Pina, P., Collignon, A., Allouch, P., on behalf of the ColBVH Study Group, (2006). New Real-Time PCR Assay Using Locked Nucleic Acid Probes To Assess Prevalence of ParC Mutations in Fluoroquinolone-Susceptible Streptococcus pneumoniae Isolates from France.. Antimicrob. Agents Chemother. 50: 1594-1598 [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]  
  • Varon, E., Houssaye, S., Grondin, S., Gutmann, L., the Groupe des Observatoires de la Resistance du P, (2006). Nonmolecular Test for Detection of Low-Level Resistance to Fluoroquinolones in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 50: 572-579 [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]  
  • Canton, R., Morosini, M., Enright, M. C., Morrissey, I. (2003). Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant Streptococcus pneumoniae: data from the global PROTEKT surveillance programme. J Antimicrob Chemother 52: 944-952 [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]  
  • Yokota, S.-i., Sato, K., Kuwahara, O., Habadera, S., Tsukamoto, N., Ohuchi, H., Akizawa, H., Himi, T., Fujii, N. (2002). Fluoroquinolone-Resistant Streptococcus pneumoniae Strains Occur Frequently in Elderly Patients in Japan. Antimicrob. Agents Chemother. 46: 3311-3315 [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]  
  • Lampidis, R., Kostrewa, D., Hof, H. (2002). Molecular characterization of the genes encoding DNA gyrase and topoisomerase IV of Listeria monocytogenes. J Antimicrob Chemother 49: 917-924 [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]  
  • Li, X., Zhao, X., Drlica, K. (2002). Selection of Streptococcus pneumoniae Mutants Having Reduced Susceptibility to Moxifloxacin and Levofloxacin. Antimicrob. Agents Chemother. 46: 522-524 [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]  
  • Canu, A., Malbruny, B., Coquemont, M., Davies, T. A., Appelbaum, P. C., Leclercq, R. (2002). Diversity of Ribosomal Mutations Conferring Resistance to Macrolides, Clindamycin, Streptogramin, and Telithromycin in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46: 125-131 [Abstract] [Full Text]  
  • Fluit, A. C., Visser, M. R., Schmitz, F.-J. (2001). Molecular Detection of Antimicrobial Resistance. Clin. Microbiol. Rev. 14: 836-871 [Abstract] [Full Text]  
  • Hartman-Neumann, S., DenBleyker, K., Pelosi, L. A., Lawrence, L. E., Barrett, J. F., Dougherty, T. J. (2001). Selection and Genetic Characterization of Streptococcus pneumoniae Mutants Resistant to the Des-F(6) Quinolone BMS-284756. Antimicrob. Agents Chemother. 45: 2865-2870 [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]  
  • 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]  
  • 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]  
  • 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]  
  • Jones, M. E., Staples, A. M., Critchley, I., Thornsberry, C., Heinze, P., Engler, H. D., Sahm, D. F. (2000). Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States. Antimicrob. Agents Chemother. 44: 2645-2652 [Abstract] [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]  
  • 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]  
  • Beyer, R., Pestova, E., Millichap, J. J., Stosor, V., Noskin, G. A., Peterson, L. R. (2000). A Convenient Assay for Estimating the Possible Involvement of Efflux of Fluoroquinolones by Streptococcus pneumoniae and Staphylococcus aureus: Evidence for Diminished Moxifloxacin, Sparfloxacin, and Trovafloxacin Efflux. Antimicrob. Agents Chemother. 44: 798-801 [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»