{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:46:29Z","timestamp":1773967589138,"version":"3.50.1"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-LABX-62-IBEID, ANR-20-CE15-0013"],"award-info":[{"award-number":["ANR-10-LABX-62-IBEID, ANR-20-CE15-0013"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015510","name":"Infrastructures en Biologie Sant\u00e9 et Agronomie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Multidrug-resistant (MDR) strains of\n Mycobacterium tuberculosis<\/jats:italic>\n represent an obstacle to eradicating tuberculosis (TB) due to the low treatment success rate of MDR TB. Among them, the MDR B0\/W148 clone has recently evolved from the\n M. tuberculosis<\/jats:italic>\n Beijing lineage 2 and is widely disseminated in Russia and Europe. To get more insights into the genetic factors underlying the evolutionary success of the MDR\n M. tuberculosis<\/jats:italic>\n B0\/W148 clone in addition to environmental and patient-related features, we focused on two mutations specific to this clone that are found in the transcriptional regulators WhiB6 and KdpDE and investigated in a H37Rv strain background the transcriptional profile associated with these mutations and their impact on the\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n growth characteristics. Through the construction and use of H37Rv\u2206\n whiB6<\/jats:italic>\n , H37Rv\u2206\n kdpDE<\/jats:italic>\n , and complemented strains, neither mutation impaired the\n in vitro<\/jats:italic>\n growth of\n M. tuberculosis<\/jats:italic>\n in standard mycobacterial growth media. The mutation T51P in\n whiB6<\/jats:italic>\n prevented the upregulation of 9 genes in the\n esx-1<\/jats:italic>\n core region and 44 genes elsewhere in the genome, while the deletion of two nucleotides in\n kdpD<\/jats:italic>\n leads to a fusion protein of KdpD with KdpE that inhibits the transcriptional activity of KdpE. Neither mutation led to hypervirulence in a mouse infection model. These results point to the role of other MDR B0\/W148 specific mutations in the wide geographic diffusion of this clone and\/or put in question a hypothesized hypervirulence as a driving factor for this large dissemination.\n <\/jats:p>\n <\/jats:sec>\n \n IMPORTANCE<\/jats:title>\n \n Human tuberculosis (TB), caused by the bacterium\n Mycobacterium tuberculosis<\/jats:italic>\n , remains a global public health issue estimated to have been responsible for 1.25 million deaths in 2023. Multidrug-resistant (MDR) strains of\n M. tuberculosis<\/jats:italic>\n , 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\n M. tuberculosis<\/jats:italic>\n 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\n M. tuberculosis<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/spectrum.03224-24","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T09:00:43Z","timestamp":1747904443000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the role of\n whiB6<\/i>\n and\n kdpDE<\/i>\n in the dominant multidrug-resistant clone\n Mycobacterium tuberculosis<\/i>\n B0\/W148"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4569-147X","authenticated-orcid":true,"given":"Isabelle","family":"Bonnet","sequence":"first","affiliation":[{"name":"Cimi-Paris, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Sorbonne Universit\u00e9","place":["Paris, France"]},{"name":"Centre National de 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