ArticleAntimicrobial agents and chemotherapy2003
Topoisomerase targeting with and resistance to gemifloxacin in Staphylococcus aureus.
Article in Antimicrobial agents and chemotherapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 30 citations in OpenAlex.
- Optimization of gemifloxacin immediate-release tablets using quality by design.Journal of food and drug analysis · 2026Article
- Efflux pump gene amplifications bypass necessity of multiple target mutations for resistance against dual-targeting antibiotic.Nature communications · 2023Article
- In vitro and in vivo profiles of ACH-702, an isothiazoloquinolone, against bacterial pathogens.Antimicrobial agents and chemotherapy · 2011Article
- Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone inhibitor of bacterial type II topoisomerases.Antimicrobial agents and chemotherapy · 2008Article
- Dual targeting of DNA gyrase and topoisomerase IV: target interactions of heteroaryl isothiazolones in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2007Article
- Dual targeting of GyrB and ParE by a novel aminobenzimidazole class of antibacterial compounds.Antimicrobial agents and chemotherapy · 2007Article
- Response of Staphylococcus aureus to salicylate challenge.Journal of bacteriology · 2007Article
- The anti-methicillin-resistant Staphylococcus aureus quinolone WCK 771 has potent activity against sequentially selected mutants, has a narrow mutant selection window against quinolone-resistant Staphylococcus aureus, and preferentially targets DNA gyrase.Antimicrobial agents and chemotherapy · 2006Article
- DX-619, a novel des-fluoro(6) quinolone manifesting low frequency of selection of resistant Staphylococcus aureus mutants: quinolone resistance beyond modification of type II topoisomerases.Antimicrobial agents and chemotherapy · 2005Article
- Novel Ser79Leu and Ser81Ile substitutions in the quinolone resistance-determining regions of ParC topoisomerase IV and GyrA DNA gyrase subunits from recent fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates.Antimicrobial agents and chemotherapy · 2005Article
- 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.Antimicrobial agents and chemotherapy · 2005Article
- Antistaphylococcal activity of WCK 771, a tricyclic fluoroquinolone, in animal infection models.Antimicrobial agents and chemotherapy · 2004Article
- Quinolone resistance due to reduced target enzyme expression.Journal of bacteriology · 2003Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Gemifloxacin, a novel quinolone with potent activity against Staphylococcus aureus, was 8- to 16-fold more active against wild-type S. aureus than ciprofloxacin. The two- to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 x 10(-11) to 1.1 x 10(-10)), suggested similar targeting of the two enzymes by gemifloxacin. Dual mutations in both gyrase and topoisomerase IV caused a 64- to 128-fold increase in the MIC of gemifloxacin, similar to that seen with ciprofloxacin. Gemifloxacin also had similar activity in vitro against topoisomerase IV and gyrase purified from S. aureus (50% inhibitory concentrations of 0.25 and 0.31 micro g/ml, respectively). This activity was 10- to 20-fold higher than that of ciprofloxacin for topoisomerase IV and 33-fold higher than that for gyrase. In contrast to the in vitro findings, only topoisomerase IV mutants were selected in first-step mutants. Overexpression of the NorA efflux pump had a minimal effect on resistance to gemifloxacin, and a mutation in the promoter region of the gene for NorA was selected only in the sixth step of serial selection of mutants. Our data show that although gemifloxacin targets purified topoisomerase IV and gyrase similarly in vitro, topoisomerase IV is the preferred target in the bacteria. Selection of novel resistance mutations in grlA requires further expansion of quinolone-resistance-determining regions, and their study may provide increased insight into enzyme-quinolone interactions.
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