{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T05:13:49Z","timestamp":1761455629904,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011033","name":"State Research Agency","doi-asserted-by":"publisher","award":["PCI2019-103488\/AEI\/10.13039\/501100011033","PID2020-112865RBI00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PCI2019-103488\/AEI\/10.13039\/501100011033","PID2020-112865RBI00\/AEI\/10.13039\/501100011033"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Carlos III Institute of Health","doi-asserted-by":"crossref","award":["FIS PI17\/00159"],"award-info":[{"award-number":["FIS PI17\/00159"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["FI18\/00036"],"award-info":[{"award-number":["FI18\/00036"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministry of Science, Innovation and Universities","doi-asserted-by":"publisher","award":["FPU2020\/01676"],"award-info":[{"award-number":["FPU2020\/01676"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Mismatch repair (MMR) system alterations can trigger transient hypermutation, promoting adaptive mutations under stress, such as antibiotic exposure. While most organisms use MutS and MutL protein families for MMR, many archaea and actinobacteria, including the major human pathogen Mycobacterium tuberculosis, lack these components and instead rely on NucS, a structurally distinct enzyme driving a non-canonical MMR pathway. Given the role of MMR in mutation control, understanding how nucS expression is regulated could be essential for uncovering the molecular basis of antibiotic resistance development in mycobacteria. In this study, we characterized the nucS promoter and transcription start site in Mycobacterium smegmatis. We found that nucS expression declines during the stationary phase in both M. smegmatis and M. tuberculosis, paralleling replication activity and canonical MMR downregulation. Our data suggest that the alternative sigma factor \u03c3B may negatively regulate nucS expression during this phase. Additionally, we identified candidate compounds that may modulate nucS expression, underscoring its responsiveness to environmental cues. These findings enhance our understanding of mycobacterial stress responses and lay the groundwork for exploring antibiotic resistance mechanisms. Strikingly, our work reveals a case of double convergent evolution: both canonical (MutS\/MutL) and non-canonical (NucS) pathways have independently evolved not only the same DNA repair function, but also similar regulatory frameworks for genome integrity preservation under stress conditions.<\/jats:p>","DOI":"10.3390\/antibiotics14111065","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:34:38Z","timestamp":1761284078000},"page":"1065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of the Expression of nucS, a Key Component of the Mismatch Repair System in Mycobacteria"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-387X","authenticated-orcid":false,"given":"Esmeralda","family":"Cebri\u00e1n-Sastre","sequence":"first","affiliation":[{"name":"Department of Microbial Biotechnology, National Center for Biotechnology (CNB)-CSIC, 28049 Madrid, Spain"},{"name":"Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen, Denmark"},{"name":"The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngel","family":"Ruiz-Enamorado","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, National Center for Biotechnology (CNB)-CSIC, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Casta\u00f1eda-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, National Center for Biotechnology (CNB)-CSIC, 28049 Madrid, Spain"},{"name":"National Center of Microbiology, Carlos III Institute of Health (CNM-ISCIII), Majadahonda, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Gola","sequence":"additional","affiliation":[{"name":"Department of Medical Technology and Biotechnology, Ernst-Abbe-Hochschule Jena, University of Applied Sciences, 07745 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Garc\u00eda-Bravo","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, National Center for Biotechnology (CNB)-CSIC, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-2010","authenticated-orcid":false,"given":"Leonor","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, National Center for Biotechnology (CNB)-CSIC, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0495-3848","authenticated-orcid":false,"given":"Jes\u00fas","family":"Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, National Center for Biotechnology (CNB)-CSIC, 28049 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/10409230701648494","article-title":"Stress-Induced Mutagenesis in Bacteria","volume":"42","author":"Foster","year":"2007","journal-title":"Crit. 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