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TitleExtensive natural variation in bacterial ribosomal drug-binding sites.
Journal, issue, pagesCell Rep, Vol. 44, Issue 7, Page 115878, Year 2025
Publish dateJul 22, 2025
AuthorsChinenye L Ekemezie / Lewis I Chan / Charlotte R Brown / Karla Helena-Bueno / Tom A Williams / Sergey V Melnikov /
PubMed AbstractRibosomes from certain bacteria possess divergent drug-binding sites compared to those of Escherichia coli, leading to natural evasion or hypersensitivity to antibiotics. However, in the absence of ...Ribosomes from certain bacteria possess divergent drug-binding sites compared to those of Escherichia coli, leading to natural evasion or hypersensitivity to antibiotics. However, in the absence of systematic studies, it is unknown whether this divergence is rare or common among bacterial species. Here, we address this by reconstructing the evolutionary history of drug-binding residues in bacterial ribosomes. We find that many rRNA residues that are currently viewed as bacterial-specific features of ribosomal drug-binding sites are in fact conserved only in a subset of bacteria. Conversely, species with divergent drug-binding sites are widespread in nature, arising from ancient rRNA polymorphisms at the direct ribosome-drug interface. Using a few bacterial species harboring divergent drug-binding sites, we identify their intrinsic resistance to corresponding ribosome-targeting antibiotics. Overall, we reveal the extensive lineage-specific diversity of ribosomal drug-binding sites, offering a resource for developing more targeted antibiotics and enabling personalized drug selection for specific pathogens.
External linksCell Rep / PubMed:40536873
MethodsEM (single particle)
Resolution3.13 Å
Structure data

53347

9qt5

EMDB-53347, PDB-9qt5:
Structure of the 50S ribosomal subunit from the antibiotic-producing bacterium Streptomyces fradiae
Method: EM (single particle) / Resolution: 3.13 Å

Source
  • streptomyces fradiae atcc 10745 = dsm 40063 (bacteria)
KeywordsRIBOSOME / Streptomyces / 50S / ribosome-targeting antibiotics

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