ArticleNucleic acids research2021
Mechanistic insights into translation inhibition by aminoglycoside antibiotic arbekacin.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Plazomicin: A promising novel antimicrobial in the era of bacterial resistance (Review).Experimental and therapeutic medicine · 2026Review
- Basis for selective drug evasion of an aminoglycoside-resistance ribosomal RNA modification.Nature communications · 2025Article
- Antibiotic-Induced Bacterial Cell Death: A "Radical" Way of Dying?Current topics in microbiology and immunology · 2025Article
- Structure-function comparison of Arbekacin with other aminoglycosides elucidates its higher potency as bacterial translation inhibitor.Scientific reports · 2025Article
- Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome.Nature communications · 2023Article
- Insights into translocation mechanism and ribosome evolution from cryo-EM structures of translocation intermediates of Giardia intestinalis.Nucleic acids research · 2023Article
- Synthesis of 6″-Modified Kanamycin A Derivatives and Evaluation of Their Antibacterial Properties.Pharmaceutics · 2023Article
- Antibiotic thermorubin tethers ribosomal subunits and impedes A-site interactions to perturb protein synthesis in bacteria.Nature communications · 2023Article
- Lamotrigine compromises the fidelity of initiator tRNA recruitment to the ribosomal P-site by IF2 and the RbfA release from 30S ribosomes inRNA biology · 2023Article
- A mini-review: environmental and metabolic factors affecting aminoglycoside efficacy.World journal of microbiology & biotechnology · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How aminoglycoside antibiotics limit bacterial growth and viability is not clearly understood. Here we employ fast kinetics to reveal the molecular mechanism of action of a clinically used, new-generation, semisynthetic aminoglycoside Arbekacin (ABK), which is designed to avoid enzyme-mediated deactivation common to other aminoglycosides. Our results portray complete picture of ABK inhibition of bacterial translation with precise quantitative characterizations. We find that ABK inhibits different steps of translation in nanomolar to micromolar concentrations by imparting pleotropic effects. ABK binding stalls elongating ribosomes to a state, which is unfavorable for EF-G binding. This prolongs individual translocation step from ∼50 ms to at least 2 s; the mean time of translocation increases inversely with EF-G concentration. ABK also inhibits translation termination by obstructing RF1/RF2 binding to the ribosome. Furthermore, ABK decreases accuracy of mRNA decoding (UUC vs. CUC) by ∼80 000 fold, causing aberrant protein production. Importantly, translocation and termination events cannot be completely stopped even with high ABK concentration. Extrapolating our kinetic model of ABK action, we postulate that aminoglycosides impose bacteriostatic effect mainly by inhibiting translocation, while they become bactericidal in combination with decoding errors.
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