Development of tolerance to bedaquiline by overexpression of trypanosomal acetate: succinate CoA transferase in Mycobacterium smegmatis.
| dc.rights.license | open | en_US |
| dc.contributor.author | BUNDUTIDI, Gloria Mavinga | |
| dc.contributor.author | MOCHIZUKI, Kota | |
| dc.contributor.author | MATSUO, Yuichi | |
| dc.contributor.author | HAYASHISHITA, Mizuki | |
| dc.contributor.author | SAKURA, Takaya | |
| dc.contributor.author | ANDO, Yuri | |
| dc.contributor.author | COOK, Gregory Murray | |
| dc.contributor.author | RAJIB, Acharjee | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | BRINGAUD, Frédéric | |
| dc.contributor.author | BOSHART, Michael | |
| dc.contributor.author | HAMANO, Shinjiro | |
| dc.contributor.author | SEKIJIMA, Masakazu | |
| dc.contributor.author | HIRAYAMA, Kenji | |
| dc.contributor.author | KITA, Kiyoshi | |
| dc.contributor.author | INAOKA, Daniel Ken | |
| dc.date.accessioned | 2025-02-10T09:04:49Z | |
| dc.date.available | 2025-02-10T09:04:49Z | |
| dc.date.issued | 2025-02-06 | |
| dc.identifier.issn | 2399-3642 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/204774 | |
| dc.description.abstractEn | The F-type ATP synthase inhibitor bedaquiline (BDQ) is a potent inhibitor of mycobacterial growth and this inhibition cannot be rescued by fermentable carbon sources that would supply ATP by an alternative pathway (substrate level phosphorylation). To gain mechanistic insight into this phenomenon, we employed a metabolic engineering approach. We introduced into Mycobacterium smegmatis an alternative ATP production pathway by substrate-level phosphorylation, specifically through overexpression of trypanosomal acetate:succinate co-enzyme A (CoA) transferase (ASCT). Intriguingly, the overexpression of ASCT partially restored intracellular ATP levels and resulted in acquired tolerance to BDQ growth inhibition at low, but not high concentrations of BDQ. These results implicate intracellular ATP levels in modulating the growth inhibitory activity of BDQ at low concentrations. These findings shed light on the intricate interplay between BDQ and mycobacterial energy metabolism, while also providing a novel tool for the development of next-generation ATP synthase-specific inhibitors targeting mycobacteria. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject.en | Diarylquinolines | |
| dc.subject.en | Mycobacterium smegmatis | |
| dc.subject.en | Coenzyme A-Transferases | |
| dc.subject.en | Adenosine Triphosphate | |
| dc.subject.en | Trypanosoma brucei brucei | |
| dc.subject.en | Bacterial Proteins | |
| dc.subject.en | Antitubercular Agents | |
| dc.title.en | Development of tolerance to bedaquiline by overexpression of trypanosomal acetate: succinate CoA transferase in Mycobacterium smegmatis. | |
| dc.title.alternative | Commun Biol | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1038/s42003-025-07611-0 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Microbiologie et Parasitologie | en_US |
| dc.identifier.pubmed | 39915674 | en_US |
| bordeaux.journal | Communications Biology | en_US |
| bordeaux.page | 187 | en_US |
| bordeaux.volume | 8 | en_US |
| bordeaux.hal.laboratories | MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | pubmed | |
| hal.identifier | hal-04937518 | |
| hal.version | 1 | |
| hal.date.transferred | 2025-02-10T09:04:55Z | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| workflow.import.source | pubmed | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Communications%20Biology&rft.date=2025-02-06&rft.volume=8&rft.issue=1&rft.spage=187&rft.epage=187&rft.eissn=2399-3642&rft.issn=2399-3642&rft.au=BUNDUTIDI,%20Gloria%20Mavinga&MOCHIZUKI,%20Kota&MATSUO,%20Yuichi&HAYASHISHITA,%20Mizuki&SAKURA,%20Takaya&rft.genre=article |