ArticleCell chemical biology2019
Chemical Induction of Aminoglycoside Uptake Overcomes Antibiotic Tolerance and Resistance in Staphylococcus aureus.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 106 citations in OpenAlex.
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- Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment.Nature reviews. Microbiology · 2026Review
- Genome-wide screen reveals glycerol-induced aminoglycoside potentiation againstAntimicrobial agents and chemotherapy · 2025Article
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- Carbene formation as a mechanism for efficient intracellular uptake of cationic antimicrobial carbon acid polymers.Nature communications · 2025Article
- The role of bacterial metabolism in antimicrobial resistance.Nature reviews. Microbiology · 2025Review
- Anti-staphylococcal fatty acids: mode of action, bacterial resistance and implications for therapeutic application.Microbiology (Reading, England) · 2025Review
- Cell membrane-derived nanovesicles as extracellular vesicle-mimetics in wound healing.Materials today. Bio · 2025Review
- Mutations in the Staphylococcus aureus Global Regulator CodY confer tolerance to an interspecies redox-active antimicrobial.PLoS genetics · 2025Article
- Optimization ultrasonic-assisted aqueous two-phase extraction of glabridin from licorice root and its activity against the foodborne pathogen MRSA.Food chemistry: X · 2025Article
- Bakuchiol killsFrontiers in pharmacology · 2025Article
- A synthetic antibiotic class with a deeply-optimized design for overcoming bacterial resistance.Nature communications · 2024Article
- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
- Controllable self-cleaning FET self-assembled RNA-cleaving DNAzyme based DNA nanotree for culture-free Staphylococcus aureus detection.Journal of nanobiotechnology · 2024Article
- Mutations in thebioRxiv : the preprint server for biology · 2024Article
- Evolution of polyamine resistance inbioRxiv : the preprint server for biology · 2024Article
- A Methylazanediyl Bisacetamide Derivative Sensitizes Staphylococcus aureus Persisters to a Combination of Gentamicin And Daptomycin.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Aminoglycoside antibiotics require proton motive force (PMF) for bacterial internalization. In non-respiring populations, PMF drops below the level required for drug influx, limiting the utility of aminoglycosides against strict and facultative anaerobes. We recently demonstrated that rhamnolipids (RLs), biosurfactant molecules produced by Pseudomonas aeruginosa, potentiate aminoglycoside activity against Staphylococcus aureus. Here, we demonstrate that RLs induce PMF-independent aminoglycoside uptake to restore sensitivity to otherwise tolerant persister, biofilm, small colony variant, and anaerobic populations of S. aureus. Furthermore, we show that this approach represses the rise of resistance, restores sensitivity to highly resistant clinical isolates, and is effective against other Gram-positive pathogens. Finally, while other membrane-acting agents can synergize with aminoglycosides, induction of PMF-independent uptake is uncommon, and distinct to RLs among several compounds tested. In all, small-molecule induction of PMF-independent aminoglycoside uptake circumvents phenotypic tolerance, overcomes genotypic resistance, and expands the utility of aminoglycosides against intrinsically recalcitrant bacterial populations.
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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.