ArticleProceedings of the National Academy of Sciences of the United States of America2017
Kinetics of drug-ribosome interactions defines the cidality of macrolide antibiotics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- Macrolide antibiotic action, resistance, and tolerance, and approaches to improve their activity against Gram-negative bacteria.The Journal of antibiotics · 2026Review
- The post antibiotic effect of streptogramins on gram-positive bacteria primarily arises from the type a component.Microbial pathogenesis · 2026Article
- Medicinal Plants: A Promising Therapeutic Approach for Addressing Antimicrobial Resistance.International journal of molecular sciences · 2026Review
- Hybrid Antibiotics Targeting the Bacterial Ribosome.ACS central science · 2025Article
- Antibiotic-Induced Bacterial Cell Death: A "Radical" Way of Dying?Current topics in microbiology and immunology · 2025Article
- Structural studies on ribosomes of differentially macrolide-resistantLife science alliance · 2025Article
- Article
- Antechodynamics and Antechokinetics: Dynamics and Kinetics of Antibiotic Resistance Biomolecules.Biomolecules · 2025Review
- Nanomotion technology for testing azithromycin susceptibility ofMicrobiology spectrum · 2025Article
- Antibiotic killing of drug-induced bacteriostatic cells.Antimicrobial agents and chemotherapy · 2025Article
- Antibacterial compounds against non-growing and intracellular bacteria.npj antimicrobials and resistance · 2025Article
- Macrolide resistance inJAC-antimicrobial resistance · 2025Review
- Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.Nature chemical biology · 2024Article
- Inactivation of the ribosome assembly factor RimP causes streptomycin resistance and impairs motility inAntimicrobial agents and chemotherapy · 2024Article
- Differential effects of translation inhibitors onLife science alliance · 2024Article
- Fluorescent reporters give new insights into antibiotics-induced nonsense and frameshift mistranslation.Scientific reports · 2024Article
- Translation inhibition efficacy does not determine thebioRxiv : the preprint server for biology · 2023Article
- Central metabolism is a key player in E. coli biofilm stimulation by sub-MIC antibiotics.PLoS genetics · 2023Article
- Article
- New Resistance Mutations Linked to Decreased Susceptibility to Solithromycin in Streptococcus pneumoniae Revealed by Chemogenomic Screens.Antimicrobial agents and chemotherapy · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Antibiotics can cause dormancy (bacteriostasis) or induce death (cidality) of the targeted bacteria. The bactericidal capacity is one of the most important properties of antibacterial agents. However, the understanding of the fundamental differences in the mode of action of bacteriostatic or bactericidal antibiotics, especially those belonging to the same chemical class, is very rudimentary. Here, by examining the activity and binding properties of chemically distinct macrolide inhibitors of translation, we have identified a key difference in their interaction with the ribosome, which correlates with their ability to cause cell death. While bacteriostatic and bactericidal macrolides bind in the nascent peptide exit tunnel of the large ribosomal subunit with comparable affinities, the bactericidal antibiotics dissociate from the ribosome with significantly slower rates. The sluggish dissociation of bactericidal macrolides correlates with the presence in their structure of an extended alkyl-aryl side chain, which establishes idiosyncratic interactions with the ribosomal RNA. Mutations or chemical alterations of the rRNA nucleotides in the drug binding site can protect cells from macrolide-induced killing, even with inhibitor concentrations that significantly exceed those required for cell growth arrest. We propose that the increased translation downtime due to slow dissociation of the antibiotic may damage cells beyond the point where growth can be reinitiated upon the removal of the drug due to depletion of critical components of the gene-expression pathway.
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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.