ArticleProceedings of the National Academy of Sciences of the United States of America2020
Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Determination of Gentamicin C-subtypes in Inner Ear Perilymph Using Liquid Chromatography with Fluorescence Detection.Journal of pharmaceutical and biomedical analysis · 2026Article
- Article
- Identification of druggable binding sites and small molecules as modulators of TMC1.Communications biology · 2025Article
- Alteration in oxidative/nitrosative disparity and nephroprotective effect of hydroethanolic extract ofAnnals of medicine and surgery (2012) · 2025Article
- An In Vitro Oxidative Stress Model of the Human Inner Ear Using Human-Induced Pluripotent Stem Cell-Derived Otic Progenitor Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Structural and Functional Basis of GenB2 Isomerase Activity from Gentamicin Biosynthesis.ACS chemical biology · 2024Article
- Glycodiversification of gentamicins throughActa pharmaceutica Sinica. B · 2024Article
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.bioRxiv : the preprint server for biology · 2024Article
- Hyperosmotic sisomicin infusion: a mouse model for hearing loss.Scientific reports · 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
- Comparative Pharmacokinetics of Gentamicin CAntibiotics (Basel, Switzerland) · 2024Article
- Hyperosmotic Sisomicin Infusion: A Mouse Model for Hearing Loss.Research square · 2024Article
- From Polymeric Nanoformulations to Polyphenols-Strategies for Enhancing the Efficacy and Drug Delivery of Gentamicin.Antibiotics (Basel, Switzerland) · 2024Review
- PCP Auto Count: A Novel Fiji/ImageJ plug-in for automated quantification of planar cell polarity and cell counting.bioRxiv : the preprint server for biology · 2024Article
- PCP auto count: a novel Fiji/ImageJ plug-in for automated quantification of planar cell polarity and cell counting.Frontiers in cell and developmental biology · 2024Article
- Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action.Frontiers in neurology · 2024Article
- Synthesis of Gentamicins C1, C2, and C2a and Antiribosomal and Antibacterial Activity of Gentamicins B1, C1, C1a, C2, C2a, C2b, and X2.ACS infectious diseases · 2023Article
- Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss.Cells · 2022Review
- Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022Review
- In vitro and in vivo models: What have we learnt about inner ear regeneration and treatment for hearing loss?Molecular and cellular neurosciences · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Gentamicin is a potent broad-spectrum aminoglycoside antibiotic whose use is hampered by ototoxic side-effects. Hospital gentamicin is a mixture of five gentamicin C-subtypes and several impurities of various ranges of nonexact concentrations. We developed a purification strategy enabling assaying of individual C-subtypes and impurities for ototoxicity and antimicrobial activity. We found that C-subtypes displayed broad and potent in vitro antimicrobial activities comparable to the hospital gentamicin mixture. In contrast, they showed different degrees of ototoxicity in cochlear explants, with gentamicin C2b being the least and gentamicin C2 the most ototoxic. Structure-activity relationships identified sites in the C4'-C6' region on ring I that reduced ototoxicity while preserving antimicrobial activity, thus identifying targets for future drug design and mechanisms for hair cell toxicity. Structure-activity relationship data suggested and electrophysiological data showed that the C-subtypes both bind and permeate the hair cell mechanotransducer channel, with the stronger the binding the less ototoxic the compound. Finally, both individual and reformulated mixtures of C-subtypes demonstrated decreased ototoxicity while maintaining antimicrobial activity, thereby serving as a proof-of-concept of drug reformulation to minimizing ototoxicity of gentamicin in patients.
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