{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T02:16:18Z","timestamp":1788747378120,"version":"build-2803163510"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Isoniazid is widely used in the treatment of pulmonary tuberculosis, yet the mechanisms underlying its tolerance remain incompletely understood. The\n                      <jats:italic>Rv0274<\/jats:italic>\n                      gene of Mycobacterium tuberculosis, presumed to belong to the aldehyde dehydrogenase family, has been hypothesized to contribute to isoniazid tolerance.\n                      <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                      was used in this study as a surrogate model to investigate this possibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated an MSMEG_0608 knockout strain and performed drug susceptibility testing, growth curve analysis, biofilm formation assays, transcriptomic profiling, and RT-qPCR validation. Complementation with\n                      <jats:italic>Rv0274<\/jats:italic>\n                      and knockdown of\n                      <jats:italic>MSMEG_0606<\/jats:italic>\n                      were further conducted to substantiate the regulatory relationships observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The deletion of\n                      <jats:italic>MSMEG_0608<\/jats:italic>\n                      significantly impaired isoniazid tolerance. Complementation and gene knockdown experiments supported the involvement of\n                      <jats:italic>Rv0274\/MSMEG_0608<\/jats:italic>\n                      in modulating the expression of genes associated with\n                      <jats:italic>Rv0273c\/MSMEG_0606<\/jats:italic>\n                      , ultimately influencing inhA expression. These findings consistently demonstrated that\n                      <jats:italic>MSMEG_0608<\/jats:italic>\n                      is integral to the isoniazid tolerance phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our results suggest that\n                      <jats:italic>Rv0274<\/jats:italic>\n                      (\n                      <jats:italic>MSMEG_0608<\/jats:italic>\n                      ) negatively regulates genes linked to\n                      <jats:italic>Rv0273c<\/jats:italic>\n                      (\n                      <jats:italic>MSMEG_0606<\/jats:italic>\n                      ), thereby contributing to alterations in inhA expression and influencing isoniazid tolerance. This work provides preliminary mechanistic insight into INH tolerance in mycobacteria and establishes a foundation for further investigations into drug tolerance in\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1697416","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:29:04Z","timestamp":1764224944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding drug tolerance: insights into the Rv0274 gene's role in isoniazid tolerance"],"prefix":"10.3389","volume":"16","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Naifang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/1471-2180-13-223","article-title":"Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c","volume":"13","author":"Brulle","year":"2013","journal-title":"BMC Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1038\/s41467-021-21748-6","article-title":"Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis","volume":"12","author":"Chakraborty","year":"2021","journal-title":"Nat. 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