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Activities of Fluoroquinolones againstStreptococcus pneumoniae Type II Topoisomerases Purified as Recombinant Proteins

Activities of Fluoroquinolones againstStreptococcus pneumoniae Type II Topoisomerases Purified as... Activities of Fluoroquinolones against Streptococcus pneumoniae Type II Topoisomerases Purified as Recombinant Proteins Ian Morrissey 1 , * and John George 2 GR Micro Ltd., London NW1 3ER, 1 and Department of Biosciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, 2 United Kingdom ABSTRACT Streptococcus pneumoniae topoisomerase IV and DNA gyrase have been purified from a fluoroquinolone-susceptible Streptococcus pneumoniae strain, from first-step mutants showing low-level resistance to ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin, and from two clinical isolates showing intermediate- and high-level fluoroquinolone resistance by a gene cloning method that produces recombinant proteins from Escherichia coli . The concentrations of ciprofloxacin, sparfloxacin, levofloxacin, or ofloxacin required to inhibit wild-type topoisomerase IV were 8 to 16 times lower than those required to inhibit wild-type DNA gyrase. Furthermore, low-level resistance to these fluoroquinolones was entirely due to the reduced inhibitory activity of fluoroquinolones against topoisomerase IV. For all the laboratory strains, the 50% inhibitory concentration for topoisomerase IV directly correlated with the MIC. We therefore propose that with S. pneumoniae , ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin target topoisomerase IV in preference to DNA gyrase. Sitafloxacin, on the other hand, was found to be equipotent against either enzyme. This characteristic is unique for a fluoroquinolone. A reduction in the sensitivities of both topoisomerase IV and DNA gyrase are required, however, to achieve intermediate- or high-level fluoroquinolone resistance in S. pneumoniae . http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Antimicrobial Agents and Chemotherapy American Society For Microbiology

Activities of Fluoroquinolones againstStreptococcus pneumoniae Type II Topoisomerases Purified as Recombinant Proteins

Antimicrobial Agents and Chemotherapy , Volume 43 (11): 2579 – Nov 1, 1999

Activities of Fluoroquinolones againstStreptococcus pneumoniae Type II Topoisomerases Purified as Recombinant Proteins

Antimicrobial Agents and Chemotherapy , Volume 43 (11): 2579 – Nov 1, 1999

Abstract

Activities of Fluoroquinolones against Streptococcus pneumoniae Type II Topoisomerases Purified as Recombinant Proteins Ian Morrissey 1 , * and John George 2 GR Micro Ltd., London NW1 3ER, 1 and Department of Biosciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, 2 United Kingdom ABSTRACT Streptococcus pneumoniae topoisomerase IV and DNA gyrase have been purified from a fluoroquinolone-susceptible Streptococcus pneumoniae strain, from first-step mutants showing low-level resistance to ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin, and from two clinical isolates showing intermediate- and high-level fluoroquinolone resistance by a gene cloning method that produces recombinant proteins from Escherichia coli . The concentrations of ciprofloxacin, sparfloxacin, levofloxacin, or ofloxacin required to inhibit wild-type topoisomerase IV were 8 to 16 times lower than those required to inhibit wild-type DNA gyrase. Furthermore, low-level resistance to these fluoroquinolones was entirely due to the reduced inhibitory activity of fluoroquinolones against topoisomerase IV. For all the laboratory strains, the 50% inhibitory concentration for topoisomerase IV directly correlated with the MIC. We therefore propose that with S. pneumoniae , ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin target topoisomerase IV in preference to DNA gyrase. Sitafloxacin, on the other hand, was found to be equipotent against either enzyme. This characteristic is unique for a fluoroquinolone. A reduction in the sensitivities of both topoisomerase IV and DNA gyrase are required, however, to achieve intermediate- or high-level fluoroquinolone resistance in S. pneumoniae .

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Publisher
American Society For Microbiology
Copyright
Copyright © 1999 by the American society for Microbiology.
ISSN
0066-4804
eISSN
1098-6596
Publisher site
See Article on Publisher Site

Abstract

Activities of Fluoroquinolones against Streptococcus pneumoniae Type II Topoisomerases Purified as Recombinant Proteins Ian Morrissey 1 , * and John George 2 GR Micro Ltd., London NW1 3ER, 1 and Department of Biosciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, 2 United Kingdom ABSTRACT Streptococcus pneumoniae topoisomerase IV and DNA gyrase have been purified from a fluoroquinolone-susceptible Streptococcus pneumoniae strain, from first-step mutants showing low-level resistance to ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin, and from two clinical isolates showing intermediate- and high-level fluoroquinolone resistance by a gene cloning method that produces recombinant proteins from Escherichia coli . The concentrations of ciprofloxacin, sparfloxacin, levofloxacin, or ofloxacin required to inhibit wild-type topoisomerase IV were 8 to 16 times lower than those required to inhibit wild-type DNA gyrase. Furthermore, low-level resistance to these fluoroquinolones was entirely due to the reduced inhibitory activity of fluoroquinolones against topoisomerase IV. For all the laboratory strains, the 50% inhibitory concentration for topoisomerase IV directly correlated with the MIC. We therefore propose that with S. pneumoniae , ciprofloxacin, sparfloxacin, levofloxacin, and ofloxacin target topoisomerase IV in preference to DNA gyrase. Sitafloxacin, on the other hand, was found to be equipotent against either enzyme. This characteristic is unique for a fluoroquinolone. A reduction in the sensitivities of both topoisomerase IV and DNA gyrase are required, however, to achieve intermediate- or high-level fluoroquinolone resistance in S. pneumoniae .

Journal

Antimicrobial Agents and ChemotherapyAmerican Society For Microbiology

Published: Nov 1, 1999

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