ArticleAntimicrobial agents and chemotherapy2019
Rapid Evolution of Reduced Susceptibility against a Balanced Dual-Targeting Antibiotic through Stepping-Stone Mutations.
Article in Antimicrobial agents and chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Efficacy andAntimicrobial agents and chemotherapy · 2025Trial
- Efficacy andAntimicrobial agents and chemotherapy · 2025Trial
- Predicting resistance evolution to guide antibiotic development.Nature reviews. Microbiology · 2026Review
- Characterization of isolates from two phase 3 uncomplicated urinary tract infection trials (EAGLE-2 and EAGLE-3) that show an apparent ≥4-fold increase in gepotidacin MIC between baseline and post-baseline visits.JAC-antimicrobial resistance · 2026Article
- Novel Bacterial Topoisomerase Inhibitors: A New Front in an Old War.Journal of molecular biology · 2026Review
- Probing the limits of genetic recoding using multi-omics-guided evolution.Nature communications · 2026Article
- Co-targeting Metabolic Neighbours Constraints Bacterial Adaptive Evolution.bioRxiv : the preprint server for biology · 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
- Stepwise evolution and clonal enrichment of gepotidacin resistance inAntimicrobial agents and chemotherapy · 2026Article
- Cryptic phenotypic variation emerges rapidly during the adaptive evolution of a carbapenemase.Nature ecology & evolution · 2026Article
- Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat PathogenACS infectious diseases · 2026Article
- High in vitro activity of the novel antimicrobial gepotidacin against Neisseria gonorrhoeae isolates in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021-24.The Journal of antimicrobial chemotherapy · 2026Article
- In Vitro Activity of Zoliflodacin AgainstAntibiotics (Basel, Switzerland) · 2026Article
- Gyrase and Topoisomerase IV as Antibacterial Targets for Gepotidacin and Zoliflodacin: Teaching Old Enzymes New Tricks.International journal of molecular sciences · 2026Review
- Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting againstACS infectious diseases · 2025Article
- An Rcs Stress-Based High-Throughput Screen Reveals Novel Gyrase Inhibitors as Indirect Inducers of Cell Envelope Stress in Gram-Negative Bacteria.ACS infectious diseases · 2025Article
- Idiosyncratic evolvability among single-point ribosomal mutants towards multi-aminoglycoside resistance.PLoS genetics · 2025Article
- Convergent evolution of antibiotic resistance mechanisms between pyrrolobenzodiazepines and albicidin in multidrug resistant Klebsiella pneumoniae.npj antimicrobials and resistance · 2025Article
- Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
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Authors and funding
15 authors.
Funding
Abstract
Multitargeting antibiotics, i.e., single compounds capable of inhibiting two or more bacterial targets, are generally considered to be a promising therapeutic strategy against resistance evolution. The rationale for this theory is that multitargeting antibiotics demand the simultaneous acquisition of multiple mutations at their respective target genes to achieve significant resistance. The theory presumes that individual mutations provide little or no benefit to the bacterial host. Here, we propose that such individual stepping-stone mutations can be prevalent in clinical bacterial isolates, as they provide significant resistance to other antimicrobial agents. To test this possibility, we focused on gepotidacin, an antibiotic candidate that selectively inhibits both bacterial DNA gyrase and topoisomerase IV. In a susceptible organism,
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