Evaluation of the role of <i>whiB6</i> and <i>kdpDE</i> in the dominant multidrug-resistant clone <i>Mycobacterium tuberculosis</i> B0/W148
Human tuberculosis (TB), caused by the bacterium <i>Mycobacterium tuberculosis</i>, remains a global public health issue estimated to have been responsible for 1.25 million deaths in 2023. Multidrug-resistant (MDR) strains of <i>M. tuberculosis</i>, resistant to rifampicin and isoniazid, lead to lower treatment success. Among them, the MDR B0/W148 clone has widely disseminated in Russia and Europe. To get more insights into the genetic factors underlying the evolutionary success of this clone, we investigated two strain-specific mutations found in the transcriptional regulators WhiB6 and KdpDE. By constructing and analyzing laboratory <i>M. tuberculosis</i> strains carrying these specific mutations, we found numerous changes in their transcriptional profiles, whereas we observed only a little impact of these mutations on the virulence of <i>M. tuberculosis</i> in a mouse infection model. Our study provides new insights into the transcriptional landscape of the selected MDR strains, although no direct connection to virulence could be established.
Authors
- Fadel Sayes (ORCID: https://orcid.org/0000-0001-7928-6643)
- Hugo Varet (ORCID: https://orcid.org/0000-0003-3980-4463)
- Florence Brossier (ORCID: https://orcid.org/0000-0003-4078-3380)
- Régis Tournebize (ORCID: https://orcid.org/0000-0003-3718-3130)
- Roland Brosch (ORCID: https://orcid.org/0000-0003-2587-3863)
- Nicolas Véziris (ORCID: https://orcid.org/0000-0001-5660-6544)
- Wladimir Sougakoff (ORCID: https://orcid.org/0000-0002-2447-517X)
- Aurélie Chauffour (ORCID: https://orcid.org/0000-0002-8846-5069)
- Mickael Orgeur
- Isabelle Bonnet (ORCID: https://orcid.org/0000-0002-4569-147X)
- Jan Madacki (ORCID: https://orcid.org/0000-0001-6534-4240)
- Wafa Frigui (ORCID: https://orcid.org/0000-0001-5172-7961)
- Alexandra Aubry (ORCID: https://orcid.org/0000-0003-4230-4793)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Sorbonne Université (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Laboratoire National de Référence (MA)
- Centre d'Immunologie et des Maladies Infectieuses (FR)
Publication Details
- Journal
- Microbiology Spectrum
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1128/spectrum.03224-24
- Citations
- 2
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Infrastructures en Biologie Santé et Agronomie
- Agence Nationale de la Recherche