THE HELEN AND MILTON A. KIMMELMAN CENTER FOR BIOMOLECULAR STRUCTURE AND ASSEMBLY
Israel
Citation
Journal: Nucleic Acids Res / Year: 2025 Title: Structural studies of ribosome from an anaerobic Bacteroidetes human pathogen Porphyromonas gingivalis. Authors: Disha-Gajanan Hiregange / Sarit Samiya / Danuta Mizgalska / Efrat Ben-Zeev / Miriam Waghalter / Andre Rivalta / K Shanmugha Rajan / Yehuda Halfon / Elinor Breiner-Goldstein / Igor ...Authors: Disha-Gajanan Hiregange / Sarit Samiya / Danuta Mizgalska / Efrat Ben-Zeev / Miriam Waghalter / Andre Rivalta / K Shanmugha Rajan / Yehuda Halfon / Elinor Breiner-Goldstein / Igor Kaczmarczyk / Aneta Sroka / Masato Taoka / Yuko Nobe / Toshiaki Isobe / Susanne Paukner / Ella Zimmerman / Anat Bashan / Jan Potempa / Ada Yonath / Abstract: Porphyromonas gingivalis, an anaerobic pathogen in chronic periodontitis, belongs to the Bacteroidota phylum and is associated with various virulence factors. Its antibiotic-resistant strains and its ...Porphyromonas gingivalis, an anaerobic pathogen in chronic periodontitis, belongs to the Bacteroidota phylum and is associated with various virulence factors. Its antibiotic-resistant strains and its propensity to form biofilms pose a challenge to effective treatment. To explore therapeutic avenues, we studied the high-resolution cryogenic electron microscope structures of ribosomes from the wild-type P. gingivalis W83 and the macrolide-resistant mutant strain ermΔporN. The structural analysis revealed unique features primarily at the ribosome periphery. Together with the distinctive distribution of ribosomal RNA modifications, these findings offer insights into the therapeutical potential, such as creation of novel therapeutic compounds inhibiting the specific cellular functions of the P. gingivalis ribosomes. Moreover, the high-resolution structure of the ermΔporN ribosome in its complex with the approved antibiotic lefamulin suggests its repurposing against P. gingivalis. Furthermore, we provide a foundation for additional effective strategies to treat periodontitis and associated systemic diseases.
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