ArticleAntimicrobial agents and chemotherapy2004
A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase II.
Article in Antimicrobial agents and chemotherapy, 2004. 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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Who cites it
13 citing papers in PubMed, 37 citations in OpenAlex.
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- Article
- Epididymo-orchitis caused by enteric organisms in men > 35 years old: beyond fluoroquinolones.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2018Review
- Antimicrobial Susceptibility ofFrontiers in microbiology · 2018Article
- Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities.Antibiotics (Basel, Switzerland) · 2017Review
- Population structure of multidrug resistant Klebsiella oxytoca within hospitals across the UK and Ireland identifies sharing of virulence and resistance genes with K. pneumoniae.Genome biology and evolution · 2017Article
- Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.Nature communications · 2015Article
- In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan.Antimicrobial agents and chemotherapy · 2015Article
- Moxifloxacin modifies corneal fibroblast-to-myofibroblast differentiation.British journal of pharmacology · 2013Article
- Emergence of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae in the Central African Republic: genetic characterization.BMC research notes · 2011Article
- Targeting DNA topoisomerase II in cancer chemotherapy.Nature reviews. Cancer · 2009Review
- Molecular basis of the targeting of topoisomerase II-mediated DNA cleavage by VP16 derivatives conjugated to triplex-forming oligonucleotides.Nucleic acids research · 2006Article
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 3 countries.
Funding
Abstract
Fluoroquinolones are broad-spectrum antimicrobial agents that target type II topoisomerases. Many fluoroquinolones are highly specific for bacterial type II topoisomerases and act against both DNA gyrase and topoisomerase IV. In Escherichia coli, mutations causing quinolone resistance are often found in the gene that encodes the A subunit of DNA gyrase. One common site for resistance-conferring mutations alters Ser83, and mutations to Leu or Trp result in high levels of resistance to fluoroquinolones. In the present study we demonstrate that the mutation of Ser83 to Trp in DNA gyrase (Gyr(S83W)) also results in sensitivity to agents that are potent inhibitors of eukaryotic topoisomerase II but that are normally inactive against prokaryotic enzymes. Epipodophyllotoxins, such as etoposide, teniposide and amino-azatoxin, inhibited the DNA supercoiling activity of Gyr(S83W), and the enzyme caused elevated levels of DNA cleavage in the presence of these agents. The DNA sequence preference for Gyr(S83W)-induced cleavage sites in the presence of etoposide was similar to that seen with eukaryotic type II topoisomerases. Introduction of the Gyr(S83W) mutation in E. coli strain RFM443-242 by site-directed mutagenesis sensitized it to epipodophyllotoxins and amino-azatoxin. Our results demonstrate that sensitivity to agents that target topoisomerase II is conserved between prokaryotic and eukaryotic enzymes, suggesting that drug interaction domains are also well conserved and likely occur in domains important for the biochemical activities of the enzymes.
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