{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T14:28:23Z","timestamp":1786804103722,"version":"build-2736575974"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31873014"],"award-info":[{"award-number":["31873014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024MC10"],"award-info":[{"award-number":["ZR2024MC10"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018589","name":"Youth Innovation Team Project for Talent Introduction and Cultivation in Universities of Shandong Province","doi-asserted-by":"publisher","award":["05430201"],"award-info":[{"award-number":["05430201"]}],"id":[{"id":"10.13039\/501100018589","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Weifang Special Expert Talent Program","award":["00000710"],"award-info":[{"award-number":["00000710"]}]},{"name":"Weifang Science and Technology Development Program","award":["2024JZ0014"],"award-info":[{"award-number":["2024JZ0014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: The Dormancy survival regulator (DosR), Rv3133c, is one of the key transcriptional proteins that regulate the dormancy of Mycobacterium tuberculosis (MTB), participates in various metabolic processes, and is essential for the survival of MTB in the host. MRA_0776 (homologous with Rv0767c and MSMEG_5860) belongs to the TetR family of regulators; we previously found that MRA_0776 can directly regulate the expression of dosR, although the mechanism by which MRA_0776 acts directly on dosR and other small molecules affecting the interaction of MRA_0776 with dosR has not been elucidated. Results: In the present study, primary transcriptomic analysis of a MRA_0776 overexpression strain revealed that MRA_0776 is a broad-spectrum regulatory protein and that MRA_0776 specifically binds to the dosR promoter both in vitro and in vivo. In addition, we found that a range of ligands, including lysine, arginine, tyrosine, Cu2+, Fe3+ and Pb2+, inhibited the interaction of MRA_0776 with the dosR promoter. Furthermore, molecular docking predicted that 125-Thr is likely to be a key amino acid site for the interaction of MRA_0776 with ligands. Finally, MRA_0776 promoted bacteria colonization and induced pathological damage in livers, spleens, lungs, and kidneys in mice. Conclusions: In conclusion, our analyses suggested that MRA_0776 is a pleiotropic regulator, and its overexpression can promote colonization and pathogenicity of MTB.<\/jats:p>","DOI":"10.1021\/acsomega.5c10658","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T15:05:22Z","timestamp":1771599922000},"page":"14707-14718","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of Dormancy-Associated\nGenes\n                    <i>dosR<\/i>\n                    by TetR Family Regulator MRA_0776 in\n                    <i>Mycobacterium\nTuberculosis<\/i>\n                    H37Ra"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1495-0502","authenticated-orcid":true,"given":"Shuxian","family":"Wang","sequence":"first","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1067-6205","authenticated-orcid":true,"given":"Luyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7579-3607","authenticated-orcid":true,"given":"Ruiying","family":"Wu","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1193-6746","authenticated-orcid":true,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8733-9763","authenticated-orcid":true,"given":"Mingrui","family":"Sun","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8260-0648","authenticated-orcid":true,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2738-0564","authenticated-orcid":true,"given":"Jiayin","family":"Xing","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0188-0818","authenticated-orcid":true,"given":"Ren","family":"Fang","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3621-3847","authenticated-orcid":true,"given":"Xiaotian","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9431-3468","authenticated-orcid":true,"given":"Yonghao","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8378-2540","authenticated-orcid":true,"given":"Zhaoli","family":"Li","sequence":"additional","affiliation":[{"name":"All Innovation (Beijing) Technology Co. LTD. , , ,","place":["Beijing, China, 101111"]},{"name":"Shandong Qidu Pharmaceutical Co., Ltd. , ,","place":["Zibo, China, 255000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6819-5372","authenticated-orcid":true,"given":"Ningning","family":"Song","sequence":"additional","affiliation":[{"name":"Shandong Second Medical University , , ,","place":["Weifang, China, 261053"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"2026081508091659700_cit1","unstructured":"World Health Organization\n          . Global Tuberculosis Report2024.https:\/\/iris.who.int\/handle\/10665\/379339 (accessed 02\/12\/2026)."},{"key":"2026081508091659700_cit2","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1186\/s12864-015-1696-9","article-title":"Global\nanalyses of TetR family transcriptional regulators in mycobacteria\nindicates conservation across species and diversity in regulated functions","volume":"16","author":"Balhana","year":"2015","journal-title":"BMC Genomics"},{"key":"2026081508091659700_cit3","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1128\/MMBR.00018-13","article-title":"The TetR family\nof regulators","volume":"77","author":"Cuthbertson","year":"2013","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2026081508091659700_cit4","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1111\/j.1365-2958.2007.05827.x","article-title":"A highly conserved transcriptional\nrepressor controls\na large regulon involved in lipid degradation in Mycobacterium\nsmegmatis and Mycobacterium tuberculosis","volume":"65","author":"Kendall","year":"2007","journal-title":"Mol. Microbiol."},{"key":"2026081508091659700_cit5","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1471-2180-8-38","article-title":"Study\nof the role of Mce3R on the transcription\nof mce genes of Mycobacterium tuberculosis","volume":"8","author":"Santangelo","year":"2008","journal-title":"BMC Microbiol."},{"key":"2026081508091659700_cit6","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1099\/mic.0.034538-0","article-title":"Cholesterol\nutilization in mycobacteria is controlled\nby two TetR-type transcriptional regulators: kstR and kstR2","volume":"156","author":"Kendall","year":"2010","journal-title":"Microbiology (Reading)"},{"key":"2026081508091659700_cit7","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1111\/1574-6968.12196","article-title":"bkaR is a TetR-type repressor\nthat controls an operon associated with branched-chain keto-acid metabolism\nin Mycobacteria","volume":"345","author":"Balhana","year":"2013","journal-title":"FEMS Microbiol. Lett."},{"key":"2026081508091659700_cit8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1046\/j.1365-2958.2003.03809.x","article-title":"EthR,\na repressor of\nthe TetR\/CamR family implicated in ethionamide resistance in mycobacteria,\noctamerizes cooperatively on its operator","volume":"51","author":"Engohang-Ndong","year":"2004","journal-title":"Mol.\nMicrobiol."},{"key":"2026081508091659700_cit9","doi-asserted-by":"publisher","first-page":"9340","DOI":"10.1093\/nar\/gks677","article-title":"Structural and functional\nanalysis of the transcriptional\nregulator Rv3066 of Mycobacterium tuberculosis","volume":"40","author":"Bolla","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2026081508091659700_cit10","doi-asserted-by":"publisher","first-page":"3595","DOI":"10.1093\/nar\/gky146","article-title":"HpoR, a novel c-di-GMP\neffective transcription factor, links the\nsecond messenger\u2019s regulatory function to the mycobacterial\nantioxidant defense","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2026081508091659700_cit11","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1093\/infdis\/jis601","article-title":"Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients","volume":"206","author":"Sun","year":"2012","journal-title":"J. Infect. Dis."},{"key":"2026081508091659700_cit12","doi-asserted-by":"publisher","first-page":"7270","DOI":"10.1093\/nar\/gky611","article-title":"Cyclic\ndi-GMP integrates functionally divergent transcription factors\ninto a regulation pathway for antioxidant defense","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2026081508091659700_cit13","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/nature12337","article-title":"The Mycobacterium\ntuberculosis regulatory network and hypoxia","volume":"499","author":"Galagan","year":"2013","journal-title":"Nature"},{"key":"2026081508091659700_cit14","doi-asserted-by":"publisher","first-page":"1292864","DOI":"10.3389\/fcimb.2023.1292864","article-title":"DosR\u2019s\nmultifaceted role on Mycobacterium\nbovis BCG revealed through multi-omics","volume":"13","author":"Cui","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"2026081508091659700_cit15","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.tube.2003.12.011","article-title":"The\ninfluence of reduced oxygen availability\non pathogenicity and gene expression in Mycobacterium tuberculosis","volume":"84","author":"Bacon","year":"2004","journal-title":"Tuberculosis (Edinb)"},{"key":"2026081508091659700_cit16","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1074\/mcp.M115.051151","article-title":"Profiling the Proteome\nof Mycobacterium\ntuberculosis during Dormancy and Reactivation","volume":"14","author":"Gopinath","year":"2015","journal-title":"Mol. Cell. Proteomics"},{"key":"2026081508091659700_cit17","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1186\/s12864-019-6190-3","article-title":"Multiple transcription factors co-regulate the Mycobacterium tuberculosis adaptation response to vitamin\nC","volume":"20","author":"Nandi","year":"2019","journal-title":"BMC Genomics"},{"key":"2026081508091659700_cit18","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1046\/j.1365-2958.2003.03474.x","article-title":"Rv3133c\/dosR\nis a transcription factor that mediates\nthe hypoxic response of Mycobacterium tuberculosis","volume":"48","author":"Park","year":"2003","journal-title":"Mol. Microbiol."},{"key":"2026081508091659700_cit19","doi-asserted-by":"publisher","first-page":"7400","DOI":"10.1093\/nar\/gkr375","article-title":"Comprehensive\ninsights into Mycobacterium tuberculosis DevR (DosR)\nregulon activation switch","volume":"39","author":"Chauhan","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2026081508091659700_cit20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0228967","article-title":"Computational study\nof parameter sensitivity in DevR regulated gene expression","volume":"15","author":"Das","year":"2020","journal-title":"PLoS One"},{"key":"2026081508091659700_cit21","doi-asserted-by":"publisher","first-page":"24053","DOI":"10.1074\/jbc.M112.364851","article-title":"The dormancy regulator DosR controls ribosome stability\nin hypoxic mycobacteria","volume":"287","author":"Trauner","year":"2012","journal-title":"J. Biol. Chem."},{"key":"2026081508091659700_cit22","doi-asserted-by":"publisher","first-page":"103947","DOI":"10.1016\/j.cellimm.2019.103947","article-title":"DosR antigen Rv1737c induces activation of macrophages\ndependent\non the TLR2 pathway","volume":"344","author":"Gao","year":"2019","journal-title":"Cell. Immunol."},{"key":"2026081508091659700_cit23","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1128\/JB.00926-09","article-title":"The Mycobacterium tuberculosis DosR\nregulon assists in metabolic homeostasis and enables rapid recovery\nfrom nonrespiring dormancy","volume":"192","author":"Leistikow","year":"2010","journal-title":"J. Bacteriol."},{"key":"2026081508091659700_cit24","doi-asserted-by":"publisher","first-page":"12729","DOI":"10.1074\/jbc.RA119.008252","article-title":"Cyclic di-GMP co-activates the two-component transcriptional regulator\nDevR in Mycobacterium smegmatis in response to oxidative\nstress","volume":"294","author":"Hu","year":"2019","journal-title":"J. Biol. Chem."},{"key":"2026081508091659700_cit25","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1089\/dna.2022.0282","article-title":"DosR Regulates the Transcription of the Arginine Biosynthesis\nGene Cluster by Binding to the Regulatory Sequences in Mycobacterium\nbovis Bacille Calmette-Guerin","volume":"41","author":"Cui","year":"2022","journal-title":"DNA\nCell Biol."},{"key":"2026081508091659700_cit26","doi-asserted-by":"publisher","first-page":"812","DOI":"10.3389\/fmicb.2020.00812","article-title":"Vitamin B and Vitamin\nC Affect DNA Methylation and Amino Acid Metabolism\nin Mycobacterium bovis BCG","volume":"11","author":"Song","year":"2020","journal-title":"Front. Microbiol."},{"key":"2026081508091659700_cit27","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1089\/dna.2015.3040","article-title":"New Targets and Cofactors\nfor the Transcription Factor LrpA from Mycobacterium tuberculosis","volume":"35","author":"Song","year":"2016","journal-title":"DNA Cell Biol."},{"key":"2026081508091659700_cit28","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time\nquantitative PCR and the 2\u00ad(\u2212\u0394\u0394CT) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2026081508091659700_cit29","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S1369-5274(03)00036-5","article-title":"RNA polymerase holoenzyme:\nstructure, function and\nbiological implications","volume":"6","author":"Borukhov","year":"2003","journal-title":"Curr. Opin. Microbiol."},{"key":"2026081508091659700_cit30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011622","article-title":"Characterization\nof a Clp protease gene regulator and the reaeration response in Mycobacterium tuberculosis","volume":"5","author":"Sherrid","year":"2010","journal-title":"PLoS One"},{"key":"2026081508091659700_cit31","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/1741-7007-8-123","article-title":"Q&A:\nAntibiotic resistance: where does it come from and what can we do\nabout it?","volume":"8","author":"Wright","year":"2010","journal-title":"BMC Biol."},{"key":"2026081508091659700_cit32","doi-asserted-by":"publisher","first-page":"34514","DOI":"10.1074\/jbc.M113.516385","article-title":"WhiB7, an Fe-S-dependent transcription factor that activates species-specific\nrepertoires of drug resistance determinants in actinobacteria","volume":"288","author":"Ramo\u0301n-Garci\u0301a","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2026081508091659700_cit33","doi-asserted-by":"publisher","first-page":"105607","DOI":"10.1016\/j.compbiomed.2022.105607","article-title":"A multidrug efflux\nprotein in Mycobacterium tuberculosis; tap as a potential\ndrug target for drug repurposing","volume":"146","author":"Dwivedi","year":"2022","journal-title":"Comput. Biol.\nMed."},{"key":"2026081508091659700_cit34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054717","article-title":"Global transcriptional\nprofiling of longitudinal clinical isolates of Mycobacterium tuberculosis\nexhibiting rapid accumulation of drug resistance","volume":"8","author":"Chatterjee","year":"2013","journal-title":"PLoS One"},{"key":"2026081508091659700_cit35","doi-asserted-by":"publisher","first-page":"1360880","DOI":"10.3389\/fcimb.2024.1360880","article-title":"The role of transcriptional\nregulators in metal ion\nhomeostasis of Mycobacterium tuberculosis","volume":"14","author":"Wang","year":"2024","journal-title":"Front.\nCell. Infect. Microbiol."},{"key":"2026081508091659700_cit36","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1111\/mmi.12256","article-title":"The role\nof zinc in the interplay\nbetween pathogenic streptococci and their hosts","volume":"88","author":"Shafeeq","year":"2013","journal-title":"Mol. Microbiol."},{"key":"2026081508091659700_cit37","doi-asserted-by":"publisher","first-page":"2118","DOI":"10.3390\/ijms22042118","article-title":"A Role\nfor Mycobacterium tuberculosis Sigma\nFactor C in Copper Nutritional Immunity","volume":"22","author":"Grosse-Siestrup","year":"2021","journal-title":"Int.\nJ. Mol. Sci."},{"key":"2026081508091659700_cit38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005883","article-title":"Decoding the similarities\nand differences\namong mycobacterial species","volume":"11","author":"Malhotra","year":"2017","journal-title":"PLoS Negl Trop\nDis"},{"key":"2026081508091659700_cit39","doi-asserted-by":"publisher","first-page":"11394","DOI":"10.1038\/s41598-019-47905-y","article-title":"Genome-wide Phenotypic\nProfiling Identifies and Categorizes Genes Required for Mycobacterial\nLow Iron Fitness","volume":"9","author":"Dragset","year":"2019","journal-title":"Sci. Rep"},{"key":"2026081508091659700_cit40","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02401-20","article-title":"A Mycobacterial Systems Resource for the Research Community","volume":"12","author":"Judd","year":"2021","journal-title":"mBio"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.5c10658","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/9\/14707\/63268458\/ao5c10658.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/9\/14707\/63268458\/ao5c10658.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T13:48:21Z","timestamp":1786801701000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/9\/14707\/5078887\/Regulation-of-Dormancy-Associated-Genes-dosR-by"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,2,20]]},"published-print":{"date-parts":[[2026,3,10]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.5c10658","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]}}}