ArticleAntimicrobial agents and chemotherapy2000
Selective targeting of topoisomerase IV and DNA gyrase in Staphylococcus aureus: different patterns of quinolone-induced inhibition of DNA synthesis.
Article in Antimicrobial agents and chemotherapy, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 104 citations in OpenAlex.
- Novel Bacterial Topoisomerase Inhibitors: A New Front in an Old War.Journal of molecular biology · 2026Review
- Current Recommendations, Antibiotic Resistance, and Emerging Treatments for Gram-Positive Ocular Infections in the United States.Antibiotics (Basel, Switzerland) · 2026Review
- Hemoglobin-crosslinked drug-loaded silk fibroin porous scaffold for long-segment tracheal defect repair: An integrated strategy leveraging dynamic mechanical biomimicry and infection control.Bioactive materials · 2026Article
- Gyrase and Topoisomerase IV as Antibacterial Targets for Gepotidacin and Zoliflodacin: Teaching Old Enzymes New Tricks.International journal of molecular sciences · 2026Review
- A Comprehensive Review on Discovery, Development, the Chemistry of Quinolones, and Their Antimicrobial Resistance.Current topics in medicinal chemistry · 2026Review
- Synthesis of Novel Thiazole/Thiadiazole Conjugates of Fluoroquinolones as Potent Antibacterial and Antimycobacterial Agents.Chemical biology & drug design · 2025Article
- Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation.JAC-antimicrobial resistance · 2024Review
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Staph wars: the antibiotic pipeline strikes back.Microbiology (Reading, England) · 2023Review
- Updated Review on Clinically-Relevant Properties of Delafloxacin.Antibiotics (Basel, Switzerland) · 2023Review
- Role of the Water-Metal Ion Bridge in Quinolone Interactions withInternational journal of molecular sciences · 2023Article
- Salmonella Central Carbon Metabolism Enhances Bactericidal Killing by Fluoroquinolone Antibiotics.Antimicrobial agents and chemotherapy · 2022Article
- The Effect of Conjugation of Ciprofloxacin and Moxifloxacin with Fatty Acids on Their Antibacterial and Anticancer Activity.International journal of molecular sciences · 2022Article
- Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents.Molecules (Basel, Switzerland) · 2021Review
- Quinolone antibiotics.MedChemComm · 2019Review
- Discovery of a Novel DNA Gyrase-Targeting Antibiotic through the Chemical Perturbation of Streptomyces venezuelae Sporulation.Cell chemical biology · 2019Article
- A brief history of antibiotics and select advances in their synthesis.The Journal of antibiotics · 2018Review
- Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities.Antibiotics (Basel, Switzerland) · 2017Review
- Activities of gyrase and topoisomerase IV on positively supercoiled DNA.Nucleic acids research · 2017Article
- Interactions between Quinolones and Bacillus anthracis Gyrase and the Basis of Drug Resistance.Biochemistry · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The effect of quinolones on the inhibition of DNA synthesis in Staphylococcus aureus was examined by using single resistance mutations in parC or gyrA to distinguish action against gyrase or topoisomerase IV, respectively. Norfloxacin preferentially attacked topoisomerase IV and blocked DNA synthesis slowly, while nalidixic acid targeted gyrase and inhibited replication rapidly. Ciprofloxacin exhibited an intermediate response, consistent with both enzymes being targeted. The absence of RecA had little influence on target choice by this assay, indicating that differences in rebound (repair) DNA synthesis were not responsible for the results. At saturating drug concentrations, norfloxacin and a gyrA mutant were used to show that topoisomerase IV-norfloxacin-cleaved DNA complexes are distributed on the S. aureus chromosome at intervals of about 30 kbp. If cleaved complexes block DNA replication, as indicated by previous work, such close spacing of topoisomerase-quinolone-DNA complexes should block replication rapidly (replication forks are likely to encounter a cleaved complex within a minute). Thus, the slow inhibition of DNA synthesis at growth-inhibitory concentrations suggests that a subset of more distantly distributed complexes is physiologically relevant for drug action and is unlikely to be located immediately in front of the DNA replication fork.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.