Structural studies of ribosome from an anaerobic Bacteroidetes human pathogen <i>Porphyromonas gingivalis</i>
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.
Authors
- Danuta Mizgalska (ORCID: https://orcid.org/0000-0003-1023-9384)
- Elinor Breiner-Goldstein
- K. Shanmugha Rajan (ORCID: https://orcid.org/0000-0003-4826-9802)
- Igor Kaczmarczyk (ORCID: https://orcid.org/0000-0002-5607-7416)
- Toshiaki Isobe (ORCID: https://orcid.org/0000-0002-0934-9298)
- Disha‐Gajanan Hiregange (ORCID: https://orcid.org/0000-0002-1291-1624)
- Ada Yonath (ORCID: https://orcid.org/0000-0002-1856-6964)
- Yuko Nobe (ORCID: https://orcid.org/0000-0001-6375-983X)
- Masato Taoka (ORCID: https://orcid.org/0000-0001-5554-4951)
- Efrat Ben‐Zeev (ORCID: https://orcid.org/0000-0001-9954-3248)
- Sarit Samiya
- Aneta Sroka (ORCID: https://orcid.org/0000-0002-3386-5364)
- Anat Bashan (ORCID: https://orcid.org/0000-0002-7705-0466)
- André Rivalta (ORCID: https://orcid.org/0000-0001-7417-1572)
- Yehuda Halfon
- Ella Zimmerman
- Susanne Paukner (ORCID: https://orcid.org/0009-0008-5594-1621)
- Jan Potempa (ORCID: https://orcid.org/0000-0002-3600-7461)
- Miriam Waghalter
Institutions
- Jagiellonian University (PL)
- University of Louisville (US)
- Nabriva Therapeutics (Austria) (AT)
- Weizmann Institute of Science (IL)
- Tokyo Metropolitan University (JP)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1093/nar/gkaf458
- Citations
- 2
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Nabriva Therapeutics
- National Institutes of Health