ArticleProceedings of the National Academy of Sciences of the United States of America2012
Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2021Pooled it
- Antibiotic-Induced Genotoxicity: Molecular Mechanisms, Cytogenetic Damage, and Implications for Human Health.International journal of molecular sciences · 2026Review
- Article
- Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus.The Journal of antimicrobial chemotherapy · 2026Article
- Multicentre preclinical profiling of apramycin for the treatment of nontuberculous mycobacteria.EBioMedicine · 2026Article
- Design, Synthesis, and Biological Evaluation of 6″-Modified Apramycin Derivatives to Overcome Aminoglycoside Resistance.Pharmaceutics · 2025Article
- Natural products influence bacteriophage infectivity.Natural product reports · 2025Review
- Selective silencing of antibiotic-tethered ribosomes as a resistance mechanism against aminoglycosides.Nature communications · 2025Article
- Translational error in mice increases with ageing in an organ-dependent manner.Nature communications · 2025Article
- Synthesis of Methyl Aprabiosaminide and 2-Hydroxyapramycin from Apramycin.Organic letters · 2025Article
- A multiparametric anti-aging CRISPR screen uncovers a role for BAF in protein synthesis regulation.Nature communications · 2025Article
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.bioRxiv : the preprint server for biology · 2024Article
- In vitro activity of apramycin (EBL-1003) in combination with colistin, meropenem, minocycline or sulbactam against XDR/PDR Acinetobacter baumannii isolates from Greece.The Journal of antimicrobial chemotherapy · 2024Article
- In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- CompleteJournal of the American Chemical Society · 2024Article
- Experimental Determination of the pACS omega · 2024Article
- Mechanistic plasticity in ApmA enables aminoglycoside promiscuity for resistance.Nature chemical biology · 2024Article
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.Frontiers in neurology · 2024Article
- Exploring antibiotic resistance mechanisms inFrontiers in microbiology · 2024Review
- Article
64 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
15 authors at 6 institutions in 5 countries.
Funding
Abstract
Aminoglycosides are potent antibacterials, but therapy is compromised by substantial toxicity causing, in particular, irreversible hearing loss. Aminoglycoside ototoxicity occurs both in a sporadic dose-dependent and in a genetically predisposed fashion. We recently have developed a mechanistic concept that postulates a key role for the mitochondrial ribosome (mitoribosome) in aminoglycoside ototoxicity. We now report on the surprising finding that apramycin, a structurally unique aminoglycoside licensed for veterinary use, shows little activity toward eukaryotic ribosomes, including hybrid ribosomes which were genetically engineered to carry the mitoribosomal aminoglycoside-susceptibility A1555G allele. In ex vivo cultures of cochlear explants and in the in vivo guinea pig model of chronic ototoxicity, apramycin causes only little hair cell damage and hearing loss but it is a potent antibacterial with good activity against a range of clinical pathogens, including multidrug-resistant Mycobacterium tuberculosis. These data provide proof of concept that antibacterial activity can be dissected from aminoglycoside ototoxicity. Together with 3D structures of apramycin-ribosome complexes at 3.5-Å resolution, our results provide a conceptual framework for further development of less toxic aminoglycosides by hypothesis-driven chemical synthesis.
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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.