ArticleNature communications2023
Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
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- Benzoxaborole-modified azithromycins inhibit translation without inducingAntimicrobial agents and chemotherapy · 2026Article
- Klebsiella pneumoniae in the global AMR: resistance mechanisms and genomic adaptation.World journal of microbiology & biotechnology · 2026Review
- Recent trends in dual-acting hybrid antibiotics and combination therapies against Gram-negative pathogens.Journal of microbiology (Seoul, Korea) · 2026Review
- Hybrid Antibiotics Targeting the Bacterial Ribosome.ACS central science · 2025Article
- Structural insights into context-specific inhibition of bacterial translation by macrolides.Nature communications · 2025Article
- Novel Macrolide Antibiotic Nafithromycin for Tackling Emerging Resistance in Respiratory Pathogens Encountered in India.Current microbiology · 2025Review
- 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
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- Creation of a macrolide antibiotic against non-tuberculousScience advances · 2025Article
- Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.Nature chemical biology · 2024Article
- A Broad Spectrum Lasso Peptide Antibiotic Targeting the Bacterial Ribosome.Research square · 2024Article
- Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity.Structure (London, England : 1993) · 2024Article
- An antibiotic preorganized for ribosomal binding overcomes antimicrobial resistance.Science (New York, N.Y.) · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The ever-growing rise of antibiotic resistance among bacterial pathogens is one of the top healthcare threats today. Although combination antibiotic therapies represent a potential approach to more efficiently combat infections caused by susceptible and drug-resistant bacteria, only a few known drug pairs exhibit synergy/cooperativity in killing bacteria. Here, we discover that well-known ribosomal antibiotics, hygromycin A (HygA) and macrolides, which target peptidyl transferase center and peptide exit tunnel, respectively, can act cooperatively against susceptible and drug-resistant bacteria. Remarkably, HygA slows down macrolide dissociation from the ribosome by 60-fold and enhances the otherwise weak antimicrobial activity of the newest-generation macrolide drugs known as ketolides against macrolide-resistant bacteria. By determining a set of high-resolution X-ray crystal structures of drug-sensitive wild-type and macrolide-resistant Erm-methylated 70S ribosomes in complex with three HygA-macrolide pairs, we provide a structural rationale for the binding cooperativity of these drugs and also uncover the molecular mechanism of overcoming Erm-type resistance by macrolides acting together with hygromycin A. Altogether our structural, biochemical, and microbiological findings lay the foundation for the subsequent development of synergistic antibiotic tandems with improved bactericidal properties against drug-resistant pathogens, including those expressing erm genes.
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