Browse by author
Lookup NU author(s): Chinenye Ekemezie, Lewis Chan, Charlotte Brown, Karla Helena Bueno, Dr Sergey MelnikovORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Authors. 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.
Author(s): Ekemezie CL, Chan LI, Brown CR, Helena-Bueno K, Williams TA, Melnikov SV
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2025
Volume: 44
Issue: 7
Print publication date: 22/07/2025
Online publication date: 18/06/2025
Acceptance date: 30/05/2025
Date deposited: 25/06/2025
ISSN (print): 2639-1856
ISSN (electronic): 2211-1247
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.celrep.2025.115878
DOI: 10.1016/j.celrep.2025.115878
Data Access Statement: The cryo-EM map and structure of the 50S ribosomal subunit from S. fradiae have been deposited in the Protein Data Bank under accession numbers EMD-53347 (for the cryo-EM map) and PDB: 9QT5 (for the structure). Other data containing rRNA sequences described in this work were deposited in FigShare: https://doi.org/10.6084/m9.figshare.27370026.v1. The code used to analyze rRNA sequences was deposited in FigShare: https://doi.org/10.6084/m9.figshare.27370026.v1 as Data S8. Information about natural variation in ribosomal drug-binding residues for individual species is also available through this web interface: https://melnikovlab.com/check-your-species
Altmetrics provided by Altmetric
