ArticleMolecular biology and evolution2016
A Hybrid Drug Limits Resistance by Evading the Action of the Multiple Antibiotic Resistance Pathway.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Hybrids/Conjugates/Chimera Drugs-Antimicrobial Hybrids: Antibiotics, Antifungals, Antituberculars, Antimalarials.Current medicinal chemistry · 2026Review
- Steering and controlling evolution - from bioengineering to fighting pathogens.Nature reviews. Genetics · 2023Review
- Rejuvenating the Activity of Usual Antibiotics on Resistant Gram-Negative Bacteria: Recent Issues and Perspectives.International journal of molecular sciences · 2023Review
- Fluoroquinolones Hybrid Molecules as Promising Antibacterial Agents in the Fight against Antibacterial Resistance.Pharmaceutics · 2022Review
- Antibacterial Therapy by AgInternational journal of molecular sciences · 2021Article
- Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates.Frontiers in chemistry · 2021Review
- Dual-mechanism antibiotics.Nature microbiology · 2020Article
- Dynamics of genetic variation in transcription factors and its implications for the evolution of regulatory networks in Bacteria.Nucleic acids research · 2020Article
- Rapid Evolution of Reduced Susceptibility against a Balanced Dual-Targeting Antibiotic through Stepping-Stone Mutations.Antimicrobial agents and chemotherapy · 2019Article
- Metabolomics-Driven Exploration of the Chemical Drug Space to Predict Combination Antimicrobial Therapies.Molecular cell · 2019Article
- Drug combinations: a strategy to extend the life of antibiotics in the 21st century.Nature reviews. Microbiology · 2019Review
- Next-generation strategy for treating drug resistant bacteria: Antibiotic hybrids.The Indian journal of medical research · 2019Review
- Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?Clinical microbiology reviews · 2018Review
- Multidrug evolutionary strategies to reverse antibiotic resistance.Science (New York, N.Y.) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Hybrid drugs are a promising strategy to address the growing problem of drug resistance, but the mechanism by which they modulate the evolution of resistance is poorly understood. Integrating high-throughput resistance measurements and genomic sequencing, we compared Escherichia coli populations evolved in a hybrid antibiotic that links ciprofloxacin and neomycin B with populations evolved in combinations of the component drugs. We find that populations evolved in the hybrid gain less resistance than those evolved in an equimolar mixture of the hybrid's components, in part because the hybrid evades resistance mediated by the multiple antibiotic resistance (mar) operon. Furthermore, we find that the ciprofloxacin moiety of the hybrid inhibits bacterial growth whereas the neomycin B moiety diminishes the effectiveness of mar activation. More generally, comparing the phenotypic and genotypic paths to resistance across different drug treatments can pinpoint unique properties of new compounds that limit the emergence of resistance.
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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.