Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Pan, X. S.
	Articles by Fisher, L. M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Pan, X. S.
	Articles by Fisher, L. M.

Previous Article | Next Article

Antimicrobial Agents and Chemotherapy, 10 1996, 2321-2326, Vol 40, No. 10
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae

XS Pan, J Ambler, S Mehtar and LM Fisher
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, University of London, United Kingdom.

Ciprofloxacin-resistant mutants of Streptococcus pneumoniae 7785 were generated by stepwise selection at increasing drug concentrations. Sequence analysis of PCR products from the strains was used to examine the quinolone resistance-determining regions of the GyrA and GyrB proteins of DNA gyrase and the analogous regions of the ParC and ParE subunits of DNA topoisomerase IV. First-step mutants exhibiting low- level resistance had no detectable changes in their topoisomerase quinolone resistance-determining regions, suggesting altered permeation or another novel resistance mechanism. Nine of 10 second-step mutants exhibited an alteration in ParC at Ser-79 to Tyr or Phe or at Ala-84 to Thr. Third- and fourth-step mutants displaying high-level ciprofloxacin resistance were found to have, in addition to the ParC alteration, a change in GyrA at residues equivalent to Escherichia coli GyrA resistance hot spots Ser-83 and Asp-87 or in GyrB at Asp-435 to Asn, equivalent to E. coli Asp-426, part of a highly conserved EGDSA motif in GyrB. No ParE changes were observed. Complementary analysis of two S. pneumoniae clinical isolates displaying low-level resistance to ciprofloxacin revealed a ParC change at Ser-79 to Phe or Arg-95 to Cys but no changes in GyrA, GyrB, or ParE. A highly resistant isolate, in addition to a ParC mutation, had a GyrA alteration at the residue equivalent to E. coli Asp-87. Thus, in both laboratory strains and clinical isolates, ParC mutations preceded those in GyrA, suggesting that topoisomerase IV is a primary topoisomerase target and gyrase is a secondary target for ciprofloxacin in S. pneumoniae.

This article has been cited by other articles:

German, N., Malik, M., Rosen, J. D., Drlica, K., Kerns, R. J. (2008). Use of Gyrase Resistance Mutants To Guide Selection of 8-Methoxy-Quinazoline-2,4-Diones. Antimicrob. Agents Chemother. 52: 3915-3921 [Abstract] [Full Text]
Pan, X. S., Dias, M., Palumbo, M., Fisher, L. M. (2008). Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage. Nucleic Acids Res 36: 5516-5529 [Abstract] [Full Text]
Soejima, T., Iida, K.-i., Qin, T., Taniai, H., Seki, M., Yoshida, S.-i. (2008). Method To Detect Only Live Bacteria during PCR Amplification. J. Clin. Microbiol. 46: 2305-2313 [Abstract] [Full Text]
Balsalobre, L., de la Campa, A. G. (2008). Fitness of Streptococcus pneumoniae Fluoroquinolone-Resistant Strains with Topoisomerase IV Recombinant Genes. Antimicrob. Agents Chemother. 52: 822-830 [Abstract] [Full Text]
Davies, T. A., Leibovitz, E., Noel, G. J., McNeeley, D. F., Bush, K., Dagan, R. (2008). Characterization and Dynamics of Middle Ear Fluid and Nasopharyngeal Isolates of Streptococcus pneumoniae from 12 Children Treated with Levofloxacin. Antimicrob. Agents Chemother. 52: 378-381 [Abstract] [Full Text]
Avrain, L., Garvey, M., Mesaros, N., Glupczynski, Y., Mingeot-Leclercq, M.-P., Piddock, L. J. V., Tulkens, P. M., Vanhoof, R., Van Bambeke, F. (2007). Selection of quinolone resistance in Streptococcus pneumoniae exposed in vitro to subinhibitory drug concentrations. J Antimicrob Chemother 60: 965-972 [Abstract] [Full Text]
Gould, C. V., Sniegowski, P. D., Shchepetov, M., Metlay, J. P., Weiser, J. N. (2007). Identifying Mutator Phenotypes among Fluoroquinolone-Resistant Strains of Streptococcus pneumoniae Using Fluctuation Analysis. Antimicrob. Agents Chemother. 51: 3225-3229 [Abstract] [Full Text]
Shin, J. H., Jung, H. J., Kim, H. R., Jeong, J., Jeong, S. H., Kim, S., Lee, E. Y., Lee, J. N., Chang, C. L. (2007). Prevalence, Characteristics, and Molecular Epidemiology of Macrolide and Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae at Five Tertiary-Care Hospitals in Korea. Antimicrob. Agents Chemother. 51: 2625-2627 [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]
Leontiou, C., Watters, G. P., Gilroy, K. L., Heslop, P., Cowell, I. G., Craig, K., Lightowlers, R. N., Lakey, J. H., Austin, C. A. (2007). Differential Selection of Acridine Resistance Mutations in Human DNA Topoisomerase IIbeta Is Dependent on the Acridine Structure. Mol. Pharmacol. 71: 1006-1014 [Abstract] [Full Text]
Rozen, D. E., McGee, L., Levin, B. R., Klugman, K. P. (2007). Fitness Costs of Fluoroquinolone Resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 51: 412-416 [Abstract] [Full Text]
Kosowska-Shick, K., Credito, K. L., Pankuch, G. A., DeWasse, B., McGhee, P., Appelbaum, P. C. (2007). Multistep Resistance Selection and Postantibiotic-Effect Studies of the Antipneumococcal Activity of LBM415 Compared to Other Agents. Antimicrob. Agents Chemother. 51: 770-773 [Abstract] [Full Text]
Billal, D. S., Fedorko, D. P., Yan, S. S., Hotomi, M., Fujihara, K., Nelson, N., Yamanaka, N. (2007). In vitro induction and selection of fluoroquinolone-resistant mutants of Streptococcus pyogenes strains with multiple emm types. J Antimicrob Chemother 59: 28-34 [Abstract] [Full Text]
Wickman, P. A., Black, J. A., Smith Moland, E., Thomson, K. S., Hanson, N. D. (2006). In vitro development of resistance to DX-619 and other quinolones in enterococci. J Antimicrob Chemother 58: 1268-1273 [Abstract] [Full Text]
Fukushima, K. Y., Hirakata, Y., Sugahara, K., Yanagihara, K., Kondo, A., Kohno, S., Kamihira, S. (2006). Rapid Screening of Topoisomerase Gene Mutations by a Novel Melting Curve Analysis Method for Early Warning of Fluoroquinolone-Resistant Streptococcus pneumoniae Emergence. J. Clin. Microbiol. 44: 4553-4558 [Abstract] [Full Text]
Adam, H. J., Schurek, K. N., DeCorby, M. R., Weshnoweski, B., Vashisht, R., Karlowsky, K., Hoban, D. J., Zhanel, G. G. (2006). Comparative in vitro activity of PGE 9262932 and fluoroquinolones against Canadian clinical Streptococcus pneumoniae isolates, including molecularly characterized ciprofloxacin-resistant isolates. J Antimicrob Chemother 58: 202-204 [Abstract] [Full Text]
Kosowska-Shick, K., Credito, K., Pankuch, G. A., Lin, G., Bozdogan, B., McGhee, P., Dewasse, B., Choi, D.-R., Ryu, J. M., Appelbaum, P. C. (2006). Antipneumococcal Activity of DW-224a, a New Quinolone, Compared to Those of Eight Other Agents.. Antimicrob. Agents Chemother. 50: 2064-2071 [Abstract] [Full Text]
Oyamada, Y., Ito, H., Fujimoto, K., Asada, R., Niga, T., Okamoto, R., Inoue, M., Yamagishi, J.-i. (2006). Combination of known and unknown mechanisms confers high-level resistance to fluoroquinolones in Enterococcus faecium. J Med Microbiol 55: 729-736 [Abstract] [Full Text]
Pletz, M. W. R., Shergill, A. P., McGee, L., Beall, B., Whitney, C. G., Klugman, K. P., for the Active Bacterial Core Surveillance Team, (2006). Prevalence of First-Step Mutants among Levofloxacin-Susceptible Invasive Isolates of Streptococcus pneumoniae in the United States.. Antimicrob. Agents Chemother. 50: 1561-1563 [Abstract] [Full Text]
Pletz, M. W. R., McGee, L., Van Beneden, C. A., Petit, S., Bardsley, M., Barlow, M., Klugman, K. P. (2006). Fluoroquinolone Resistance in Invasive Streptococcus pyogenes Isolates Due to Spontaneous Mutation and Horizontal Gene Transfer. Antimicrob. Agents Chemother. 50: 943-948 [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]
Jumbe, N. L., Louie, A., Miller, M. H., Liu, W., Deziel, M. R., Tam, V. H., Bachhawat, R., Drusano, G. L. (2006). Quinolone Efflux Pumps Play a Central Role in Emergence of Fluoroquinolone Resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 50: 310-317 [Abstract] [Full Text]
Faccone, D., Andres, P., Galas, M., Tokumoto, M., Rosato, A., Corso, A. (2005). Emergence of a Streptococcus pneumoniae Clinical Isolate Highly Resistant to Telithromycin and Fluoroquinolones. J. Clin. Microbiol. 43: 5800-5803 [Abstract] [Full Text]
Fujimoto-Nakamura, M., Ito, H., Oyamada, Y., Nishino, T., Yamagishi, J.-i. (2005). Accumulation of Mutations in both gyrB and parE Genes Is Associated with High-Level Resistance to Novobiocin in Staphylococcus aureus. Antimicrob. Agents Chemother. 49: 3810-3815 [Abstract] [Full Text]
Reinert, R. R., Reinert, S., van der Linden, M., Cil, M. Y., Al-Lahham, A., Appelbaum, P. (2005). Antimicrobial Susceptibility of Streptococcus pneumoniae in Eight European Countries from 2001 to 2003. Antimicrob. Agents Chemother. 49: 2903-2913 [Abstract] [Full Text]
Kosowska, K., Hoellman, D. B., Lin, G., Clark, C., Credito, K., McGhee, P., Dewasse, B., Bozdogan, B., Shapiro, S., Appelbaum, P. C. (2005). Antipneumococcal Activity of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin. Antimicrob. Agents Chemother. 49: 1932-1942 [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]
Leo, E., Gould, K. A., Pan, X.-S., Capranico, G., Sanderson, M. R., Palumbo, M., Fisher, L. M. (2005). Novel Symmetric and Asymmetric DNA Scission Determinants for Streptococcus pneumoniae Topoisomerase IV and Gyrase Are Clustered at the DNA Breakage Site. J. Biol. Chem. 280: 14252-14263 [Abstract] [Full Text]
Pletz, M. W. R., McGee, L., Beall, B., Whitney, C. G., Klugman, K. P. (2005). Interspecies Recombination in Type II Topoisomerase Genes Is Not a Major Cause of Fluoroquinolone Resistance in Invasive Streptococcus pneumoniae Isolates in the United States. Antimicrob. Agents Chemother. 49: 779-780 [Abstract] [Full Text]
Smith, H. J., Walters, M., Hisanaga, T., Zhanel, G. G., Hoban, D. J. (2004). Mutant Prevention Concentrations for Single-Step Fluoroquinolone-Resistant Mutants of Wild-Type, Efflux-Positive, or ParC or GyrA Mutation-Containing Streptococcus pneumoniae Isolates. Antimicrob. Agents Chemother. 48: 3954-3958 [Abstract] [Full Text]
Pletz, M. W. R., McGee, L., Jorgensen, J., Beall, B., Facklam, R. R., Whitney, C. G., Klugman, K. P. (2004). Levofloxacin-Resistant Invasive Streptococcus pneumoniae in the United States: Evidence for Clonal Spread and the Impact of Conjugate Pneumococcal Vaccine. Antimicrob. Agents Chemother. 48: 3491-3497 [Abstract] [Full Text]
Croisier, D., Etienne, M., Piroth, L., Bergoin, E., Lequeu, C., Portier, H., Chavanet, P. (2004). In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants. J Antimicrob Chemother 54: 640-647 [Abstract] [Full Text]
Christiansen, K. J., Bell, J. M., Turnidge, J. D., Jones, R. N. (2004). Antimicrobial Activities of Garenoxacin (BMS 284756) against Asia-Pacific Region Clinical Isolates from the SENTRY Program, 1999 to 2001. Antimicrob. Agents Chemother. 48: 2049-2055 [Abstract] [Full Text]
Gould, K. A., Pan, X.-S., Kerns, R. J., Fisher, L. M. (2004). Ciprofloxacin Dimers Target Gyrase in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 48: 2108-2115 [Abstract] [Full Text]
Croisier, D., Etienne, M., Bergoin, E., Charles, P.-E., Lequeu, C., Piroth, L., Portier, H., Chavanet, P. (2004). Mutant Selection Window in Levofloxacin and Moxifloxacin Treatments of Experimental Pneumococcal Pneumonia in a Rabbit Model of Human Therapy. Antimicrob. Agents Chemother. 48: 1699-1707 [Abstract] [Full Text]
Harnett, S. J., Fraise, A. P., Andrews, J. M., Jevons, G., Brenwald, N. P., Wise, R. (2004). Comparative study of the in vitro activity of a new fluoroquinolone, ABT-492. J Antimicrob Chemother 53: 783-792 [Abstract] [Full Text]
Alonso, R., Galimand, M., Courvalin, P. (2004). An extended PCR-RFLP assay for detection of parC, parE and gyrA mutations in fluoroquinolone-resistant Streptococcus pneumoniae. J Antimicrob Chemother 53: 682-683 [Full Text]
Fluit, A. C., Schmitz, F.-J., Verhoef, J., Milatovic, D. (2004). In Vitro Activity of Daptomycin against Gram-Positive European Clinical Isolates with Defined Resistance Determinants. Antimicrob. Agents Chemother. 48: 1007-1011 [Abstract] [Full Text]
Pfeiffer, E. S., Hiasa, H. (2004). Replacement of ParC {alpha}4 Helix with That of GyrA Increases the Stability and Cytotoxicity of Topoisomerase IV-Quinolone-DNA Ternary Complexes. Antimicrob. Agents Chemother. 48: 608-611 [Abstract] [Full Text]
Browne, F. A., Bozdogan, B., Clark, C., Kelly, L. M., Ednie, L., Kosowska, K., Dewasse, B., Jacobs, M. R., Appelbaum, P. C. (2003). Antipneumococcal Activity of DK-507k, a New Quinolone, Compared with the Activities of 10 Other Agents. Antimicrob. Agents Chemother. 47: 3815-3824 [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]
Kuhn, F., Cottagnoud, M., Acosta, F., Flatz, L., Entenza, J., Cottagnoud, P. (2003). Cefotaxime Acts Synergistically with Levofloxacin in Experimental Meningitis Due to Penicillin-Resistant Pneumococci and Prevents Selection of Levofloxacin-Resistant Mutants In Vitro. Antimicrob. Agents Chemother. 47: 2487-2491 [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]
Morosini, M.-I., Loza, E., del Campo, R., Almaraz, F., Baquero, F., Canton, R. (2003). Fluoroquinolone-Resistant Streptococcus pneumoniae in Spain: Activities of Garenoxacin against Clinical Isolates Including Strains with Altered Topoisomerases. Antimicrob. Agents Chemother. 47: 2692-2695 [Abstract] [Full Text]
Davies, T. A., Goldschmidt, R., Pfleger, S., Loeloff, M., Bush, K., Sahm, D. F., Evangelista, A. (2003). Cross-resistance, relatedness and allele analysis of fluoroquinolone-resistant US clinical isolates of Streptococcus pneumoniae (1998-2000). J Antimicrob Chemother 52: 168-175 [Abstract] [Full Text]
Balsalobre, L., Ferrandiz, M. J., Linares, J., Tubau, F., de la Campa, A. G. (2003). Viridans Group Streptococci Are Donors in Horizontal Transfer of Topoisomerase IV Genes to Streptococcus pneumoniae. Antimicrob. Agents Chemother. 47: 2072-2081 [Abstract] [Full Text]
Drlica, K. (2003). The mutant selection window and antimicrobial resistance. J Antimicrob Chemother 52: 11-17 [Abstract] [Full Text]
Zhanel, G. G., Palatnick, L., Nichol, K. A., Bellyou, T., Low, D. E., Hoban, D. J. (2003). Antimicrobial Resistance in Respiratory Tract Streptococcus pneumoniae Isolates: Results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002. Antimicrob. Agents Chemother. 47: 1867-1874 [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]
Decousser, J.-W., Pina, P., Picot, F., Delalande, C., Pangon, B., Courvalin, P., Allouch, P., the ColBVH study group, (2003). Frequency of isolation and antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections: a French prospective national survey. J Antimicrob Chemother 51: 1213-1222 [Abstract] [Full Text]
Martin-Galiano, A. J., de la Campa, A. G. (2003). High-Efficiency Generation of Antibiotic-Resistant Strains of Streptococcus pneumoniae by PCR and Transformation. Antimicrob. Agents Chemother. 47: 1257-1261 [Abstract] [Full Text]
de la Campa, A. G., Ferrandiz, M.-J., Tubau, F., Pallares, R., Manresa, F., Linares, J. (2003). Genetic Characterization of Fluoroquinolone-Resistant Streptococcus pneumoniae Strains Isolated during Ciprofloxacin Therapy from a Patient with Bronchiectasis. Antimicrob. Agents Chemother. 47: 1419-1422 [Abstract] [Full Text]
Bui, M.-H., Stone, G. G., Nilius, A. M., Almer, L., Flamm, R. K. (2003). PCR-Oligonucleotide Ligation Assay for Detection of Point Mutations Associated with Quinolone Resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 47: 1456-1459 [Abstract] [Full Text]
Hardy, C. D., Cozzarelli, N. R. (2003). Alteration of Escherichia coli Topoisomerase IV to Novobiocin Resistance. Antimicrob. Agents Chemother. 47: 941-947 [Abstract] [Full Text]
Perez-Trallero, E., Marimon, J. M., Gonzalez, A., Iglesias, L. (2003). Spain14-5 international multiresistant Streptococcus pneumoniae clone resistant to fluoroquinolones and other families of antibiotics. J Antimicrob Chemother 51: 715-719 [Abstract] [Full Text]
Hiasa, H., Shea, M. E., Richardson, C. M., Gwynn, M. N. (2003). 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. 278: 8861-8868 [Abstract] [Full Text]
Alonso, R., Galimand, M., Courvalin, P. (2002). parC Mutation Conferring Ciprofloxacin Resistance in Streptococcus pyogenes BM4513. Antimicrob. Agents Chemother. 46: 3686-3687 [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]
Boswell, F. J., Andrews, J. M., Jevons, G., Wise, R. (2002). Comparison of the in vitro activities of several new fluoroquinolones against respiratory pathogens and their abilities to select fluoroquinolone resistance. J Antimicrob Chemother 50: 495-502 [Abstract] [Full Text]
Croisier, D., Chavanet, P., Lequeu, C., Ahanou, A., Nierlich, A., Neuwirth, C., Piroth, L., Duong, M., Buisson, M., Portier, H. (2002). Efficacy and pharmacodynamics of simulated human-like treatment with levofloxacin on experimental pneumonia induced with penicillin-resistant pneumococci with various susceptibilities to fluoroquinolones. J Antimicrob Chemother 50: 349-360 [Abstract] [Full Text]
Maurin, M., Bryskier, A., Raoult, D. (2002). Antibiotic Susceptibilities of Parachlamydia acanthamoeba in Amoebae. Antimicrob. Agents Chemother. 46: 3065-3067 [Abstract] [Full Text]
Madaras-Kelly, K. J., Daniels, C., Hegbloom, M., Thompson, M. (2002). Pharmacodynamic characterization of efflux and topoisomerase IV-mediated fluoroquinolone resistance in Streptococcus pneumoniae. J Antimicrob Chemother 50: 211-218 [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]
Pankuch, G. A., Bozdogan, B., Nagai, K., Tambic-Andrasevic, A., Schoenwald, S., Tambic, T., Kalenic, S., Plesko, S., Tepes, N. K., Kotarski, Z., Payerl-Pal, M., Appelbaum, P. C. (2002). Incidence, Epidemiology, and Characteristics of Quinolone- Nonsusceptible Streptococcus pneumoniae in Croatia. Antimicrob. Agents Chemother. 46: 2671-2675 [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]
Reinert, R. R., Al-Lahham, A., Lutticken, R., Boos, M., Schmitz, F.-J. (2002). Characterization of clinical Streptococcus pneumoniae strains from Germany with decreased susceptibility to fluoroquinolones. J Antimicrob Chemother 49: 1015-1018 [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]
Piddock, L. J. V., Johnson, M. M., Simjee, S., Pumbwe, L. (2002). Expression of Efflux Pump Gene pmrA in Fluoroquinolone-Resistant and -Susceptible Clinical Isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46: 808-812 [Abstract] [Full Text]
Yamakawa, T., Mitsuyama, J., Hayashi, K. (2002). In vitro and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone. J Antimicrob Chemother 49: 455-465 [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]
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]
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]
Pankuch, G. A., Nagai, K., Davies, T. A., Jacobs, M. R., Appelbaum, P. C. (2002). Antipneumococcal Activity of BMS 284756 Compared to Those of Six Other Agents. Antimicrob. Agents Chemother. 46: 251-254 [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]
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]
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]
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]
Boswell, F. J., Andrews, J. M., Wise, R. (2001). Comparison of the in vitro activities of BMS-284756 and four fluoroquinolones against Streptococcus pneumoniae. J Antimicrob Chemother 48: 446-447 [Full Text]
Bast, D. J., de Azavedo, J. C. S., Tam, T. Y., Kilburn, L., Duncan, C., Mandell, L. A., Davidson, R. J., Low, D. E. (2001). Interspecies Recombination Contributes Minimally to Fluoroquinolone Resistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 2631-2634 [Abstract] [Full Text]
Hsueh, P.-R., Teng, L.-J., Wu, T.-L., Ho, S.-W., Luh, K.-T. (2001). First clinical isolate of Streptococcus pneumoniae exhibiting high-level resistance to fluoroquinolones in Taiwan. J Antimicrob Chemother 48: 316-317 [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]
Maurin, M., Abergel, C., Raoult, D. (2001). DNA Gyrase-Mediated Natural Resistance to Fluoroquinolones in Ehrlichia spp.. Antimicrob. Agents Chemother. 45: 2098-2105 [Abstract] [Full Text]
Thornsberry, C., Karlowsky, J. A., Sahm, D. F., Jorgensen, J. H., Weigel, L. M., Swenson, J. M., Whitney, C. G., Tenover, F. C., Ferraro, M. J. (2001). Levofloxacin-Resistant Streptococcus pneumoniae: Second Look. Antimicrob. Agents Chemother. 45: 2183-2184 [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]
Coyle, E. A., Kaatz, G. W., Rybak, M. J. (2001). Activities of Newer Fluoroquinolones against Ciprofloxacin-Resistant Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45: 1654-1659 [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]
Ho, P. L., Yam, W. C., Que, T. L., Tsang, D. N. C., Seto, W. H., Ng, T. K., Ng, W. S. (2001). Target site modifications and efflux phenotype in clinical isolates of Streptococcus pneumoniae from Hong Kong with reduced susceptibility to fluoroquinolones. J Antimicrob Chemother 47: 655-658 [Abstract] [Full Text]
Xuan, D., Zhong, M., Mattoes, H., Bui, K. Q., McNabb, J., Nicolau, D. P., Quintiliani, R., Nightingale, C. H. (2001). Streptococcus pneumoniae Response to Repeated Moxifloxacin or Levofloxacin Exposure in a Rabbit Tissue Cage Model. Antimicrob. Agents Chemother. 45: 794-799 [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]
Janoir, C., Varon, E., Kitzis, M.-D., Gutmann, L. (2001). New Mutation in ParE in a Pneumococcal In Vitro Mutant Resistant to Fluoroquinolones. Antimicrob. Agents Chemother. 45: 952-955 [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]
Whitney, C. G., Farley, M. M., Hadler, J., Harrison, L. H., Lexau, C., Reingold, A., Lefkowitz, L., Cieslak, P. R., Cetron, M., Zell, E. R., Jorgensen, J. H., Schuchat, A., The Active Bacterial Core Surveillance Program of, (2000). Increasing Prevalence of Multidrug-Resistant Streptococcus pneumoniae in the United States. NEJM 343: 1917-1924 [Abstract] [Full Text]

Clin. Vaccine Immunol.	Clin. Microbiol. Rev.
J. Clin. Microbiol.	ALL ASM JOURNALS