ArticleAntimicrobial agents and chemotherapy2008
Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone inhibitor of bacterial type II topoisomerases.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 141 citations in OpenAlex.
- BWC0977, a broad-spectrum antibacterial clinical candidate to treat multidrug resistant infections.Nature communications · 2024Trial
- Novel Bacterial Topoisomerase Inhibitors: A New Front in an Old War.Journal of molecular biology · 2026Review
- Designing the DNA-Intercalating Moiety to Improve the Safety and Efficacy of Novel Bacterial Topoisomerase Inhibitors.Journal of medicinal chemistry · 2026Article
- Determination of frequency of spontaneous resistance for gepotidacin and levofloxacin against a collection of gram-positive and gram-negative organisms.Antimicrobial agents and chemotherapy · 2026Article
- AI-guided competitive docking for virtual screening and compound efficacy prediction.npj drug discovery · 2026Article
- Structural and Mechanistic Insights into Atypical Bacterial Topoisomerase Inhibitors.ACS medicinal chemistry letters · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Molecular mechanism of a triazole-containing inhibitor ofiScience · 2024Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.ACS medicinal chemistry letters · 2024Article
- Article
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Novel Indane-Containing NBTIs with Potent Anti-Gram-Negative Activity and Minimal hERG Inhibition.ACS medicinal chemistry letters · 2023Article
- Biofilms as Battlefield Armor for Bacteria against Antibiotics: Challenges and Combating Strategies.Microorganisms · 2023Review
- Discovery of a Series of Indane-Containing NBTIs with Activity against Multidrug-Resistant Gram-Negative Pathogens.ACS medicinal chemistry letters · 2023Article
- Exploring Alternative Pathways to Target Bacterial Type II Topoisomerases Using NBTI Antibacterials: Beyond Halogen-Bonding Interactions.Antibiotics (Basel, Switzerland) · 2023Article
- Computational and Preclinical Prediction of the Antimicrobial Properties of an Agent Isolated fromMolecules (Basel, Switzerland) · 2023Article
- Why Matter Matters: Fast-TrackingMolecules (Basel, Switzerland) · 2022Review
- The Structural Features of Novel Bacterial Topoisomerase Inhibitors That Define Their Activity on Topoisomerase IV.Journal of medicinal chemistry · 2022Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NXL101 is one of a new class of quinoline antibacterial DNA gyrase and topoisomerase IV inhibitors showing potent activity against gram-positive bacteria, including methicillin- and fluoroquinolone-resistant strains. NXL101 inhibited topoisomerase IV more effectively than gyrase from Escherichia coli, whereas the converse is true of enzymes from Staphylococcus aureus. This apparent target preference is opposite to that which is associated with most fluoroquinolone antibiotics. In vitro isolation of S. aureus mutants resistant to NXL101 followed by cloning and sequencing of the genes encoding gyrase and topoisomerase IV led to the identification of several different point mutations within, or close to, the quinolone resistance-determining region (QRDR) of GyrA. However, the mutations were not those that are most frequently associated with decreased sensitivity to quinolones. A fluoroquinolone-resistant mutant variant of gyrase generated in vitro was highly resistant to inhibition by the fluoroquinolones ciprofloxacin and moxifloxacin but remained fully susceptible to inhibition by NXL101. Two mutant gyrases constructed in vitro, with mutations in gyrA engineered according to those most frequently found in S. aureus strains resistant to NXL101, were insensitive to inhibition by NXL101 and had a diminished sensitivity to ciprofloxacin and moxifloxacin. Certain combinations of mutations giving rise to NXL101 resistance and those giving rise to fluoroquinolone resistance may be mutually exclusive.
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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.