{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:41Z","timestamp":1789625021692,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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>Background<\/jats:title>\n                    <jats:p>Drug-resistant tuberculosis (DR-TB) remains a major challenge to global tuberculosis control. In 2024, approximately 390,000 individuals developed multidrug- or rifampicin-resistant tuberculosis (MDR\/RR-TB) worldwide, while treatment coverage remained limited to 42%, highlighting persistent gaps in DR-TB management. The mechanisms underlying DR-TB involve resistance-associated mutations, bacterial adaptation, host\u2013pathogen interactions, and drug-target-related processes. A comprehensive evaluation of research trends is needed to clarify the evolution and future directions of this field.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This bibliometric review was conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) 2020 statement. Publications related to DR-TB mechanisms from January 1, 2006, to May 10, 2026, were retrieved from the Web of Science Core Collection (WoSCC), yielding 1,043 eligible records. VOSviewer, CiteSpace, and bibliometric methods were applied to analyze countries\/regions, institutions, authors, journals, keywords, and co-citation networks. An independent PubMed dataset (\n                      <jats:italic>n<\/jats:italic>\n                      = 787) was used for cross-database validation to assess the consistency and robustness of major findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Annual publications increased markedly after 2015. The dataset included 6,129 authors from 1,581 institutions across 60 countries\/regions. The United States was the leading contributor, with the highest number of publications (248) and citations (2,460). Keyword and thematic analyzes revealed that major research areas included drug resistance mechanisms, combination therapy, microbiological analysis, antitubercular agents, and\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      . Research evolution demonstrated a transition from traditional studies of bacterial pathology and biosynthesis toward computer-aided target discovery, molecular docking, and host-directed therapies involving programmed cell death pathways such as autophagy. Descriptive country\u2013institution\u2013keyword mapping showed regionally patterned thematic associations, with natural products, nanomaterials, and quorum-sensing inhibition represented among associations involving institutions from Asia and Latin America, and clinical microbiology, genomics, and pathway regulation represented among those involving institutions from North America and Europe. PubMed validation demonstrated comparable publication trends, geographic distributions, and thematic patterns.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The bibliometric landscape of DR-TB mechanism research has broadened from individual molecular targets to bacterial, host-related, and computational themes. Recent studies show increasing attention to host-directed approaches, molecular modeling, and multidimensional analyzes. These trends may inform future mechanistic and translational research, although their biological and clinical relevance requires independent validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1942089","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:40Z","timestamp":1789623100000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Global research trends in tuberculosis drug-resistance mechanisms: a bibliometric and cross-database analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiali","family":"Lian","sequence":"first","affiliation":[{"name":"School of Public Health, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailiang","family":"Nan","sequence":"additional","affiliation":[{"name":"The Fourth Hospital of Inner Mongolia Autonomous Region (Chest Hospital)","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Xing","sequence":"additional","affiliation":[{"name":"Inner Mongolia University of Science and Technology, Baotou","place":["Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanli","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Baotou Medical College, Baotou","place":["Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqi","family":"Hao","sequence":"additional","affiliation":[{"name":"School of Public Health, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Public Health, Baotou Medical College","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"612675","DOI":"10.3389\/fmicb.2021.612675","article-title":"Evolution of drug-resistant Mycobacterium tuberculosis strains and their adaptation to the human lung environment.","volume":"12","author":"Allu\u00e9-Guardia","year":"2021","journal-title":"Front. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"4590","DOI":"10.1128\/AAC.00753-16","article-title":"Mutations in pepQ confer low-level resistance to bedaquiline and clofazimine in Mycobacterium tuberculosis","volume":"60","author":"Almeida","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e102135","DOI":"10.1371\/journal.pone.0102135","article-title":"Acquired resistance of Mycobacterium tuberculosis to bedaquiline","volume":"9","author":"Andries","year":"2014","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"11786361221099878","DOI":"10.1177\/11786361221099878","article-title":"Recent progress in the development of novel Mycobacterium cell wall inhibitor to combat drug-resistant tuberculosis.","volume":"15","author":"Belete","year":"2022","journal-title":"Microbiol. Insights"},{"key":"B5","doi-asserted-by":"publisher","first-page":"762315","DOI":"10.3389\/fimmu.2021.762315","article-title":"Dissecting host-pathogen interactions in TB using systems-based omic approaches.","volume":"12","author":"Borah","year":"2021","journal-title":"Front. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"547","DOI":"10.2174\/1568026621999201211200447","article-title":"Tuberculosis: An update on pathophysiology, molecular mechanisms of drug resistance, newer anti-TB drugs, treatment regimens and host- directed therapies.","volume":"21","author":"Borah","year":"2021","journal-title":"Curr. Top Med. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"ftz037","DOI":"10.1093\/femspd\/ftz037","article-title":"The current state of animal models and genomic approaches towards identifying and validating molecular determinants of Mycobacterium tuberculosis infection and tuberculosis disease.","volume":"77","author":"Bucsan","year":"2019","journal-title":"Pathog Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3390\/metabo11020088","article-title":"Metabolic versatility of Mycobacterium tuberculosis during infection and dormancy.","volume":"11","author":"Chang","year":"2021","journal-title":"Metabolites"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e191","DOI":"10.1016\/S1473-3099(21)00808-2","article-title":"25 years of surveillance of drug-resistant tuberculosis: Achievements, challenges, and way forward.","volume":"22","author":"Dean","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41586-024-07206-5","article-title":"Compensatory evolution in NusG improves fitness of drug-resistant M. tuberculosis.","volume":"628","author":"Eckartt","year":"2024","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41579-024-01025-1","article-title":"Drug-resistant tuberculosis: A persistent global health concern.","volume":"22","author":"Farhat","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"4629","DOI":"10.3390\/app10134629","article-title":"Multi-omics technologies applied to tuberculosis drug discovery.","volume":"10","author":"Goff","year":"2020","journal-title":"Appl. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e0019425","DOI":"10.1128\/cmr.00194-25","article-title":"The power of resistance: Mechanisms of antimicrobial resistance in Mycobacterium tuberculosis and its impact on tuberculosis management.","volume":"39","author":"Gopalaswamy","year":"2026","journal-title":"Clin. Microbiol. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1085946","DOI":"10.3389\/fcimb.2022.1085946","article-title":"Tools to develop antibiotic combinations that target drug tolerance in Mycobacterium tuberculosis.","volume":"12","author":"Greenstein","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1093\/femsre\/fux011","article-title":"Antimicrobial resistance in Mycobacterium tuberculosis: Mechanistic and evolutionary perspectives.","volume":"41","author":"Gygli","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1194923","DOI":"10.3389\/fimmu.2023.1194923","article-title":"Mycobacterium tuberculosis cell-wall and antimicrobial peptides: A mission impossible?","volume":"14","author":"Jacobo-Delgado","year":"2023","journal-title":"Front. Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1089\/phage.2024.0059","article-title":"Preclinical evidence for phage therapy to treat mycobacterial infections: A narrative review.","volume":"6","author":"Janssen","year":"2025","journal-title":"PHAGE: Therapy Appl. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13040-025-00442-z","article-title":"Network-based multi-omics integrative analysis methods in drug discovery: A systematic review.","volume":"18","author":"Jiang","year":"2025","journal-title":"BioData Min."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1012295","DOI":"10.1371\/journal.ppat.1012295","article-title":"Advances in an in vitro tuberculosis infection model using human lung organoids for host-directed therapies.","volume":"20","author":"Kim","year":"2024","journal-title":"PLoS Pathog"},{"key":"B20","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1126\/science.1171583","article-title":"Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis","volume":"324","author":"Makarov","year":"2009","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2200852","DOI":"10.2807\/1560-7917.ES.2023.28.12.2200852","article-title":"A one health approach revealed the long-term role of Mycobacterium caprae as the hidden cause of human tuberculosis in a region of spain, 2003 to 2022.","volume":"28","author":"Mart\u00ednez-Lirola","year":"2023","journal-title":"Euro Surveill."},{"key":"B22","doi-asserted-by":"publisher","first-page":"111","DOI":"10.2147\/CLEP.S35839","article-title":"Extensively drug-resistant tuberculosis: Epidemiology and management.","volume":"6","author":"Matteelli","year":"2014","journal-title":"Clin. Epidemiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.tips.2021.11.016","article-title":"Host-directed therapies for tuberculosis: Quantitative systems pharmacology approaches.","volume":"43","author":"Mehta","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"954","DOI":"10.5588\/ijtld.12.0480","article-title":"Social, economic, and psychological impacts of MDR-TB treatment in tijuana, mexico: A patient\u2019s perspective.","volume":"17","author":"Morris","year":"2013","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3390\/antibiotics3030317","article-title":"Drug resistance mechanisms in Mycobacterium tuberculosis.","volume":"3","author":"Palomino","year":"2014","journal-title":"Antibiotics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1038\/s41467-023-37148-x","article-title":"A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination.","volume":"14","author":"Qiang","year":"2023","journal-title":"Nat. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1274175","DOI":"10.3389\/fcimb.2023.1274175","article-title":"Drug-resistant strains of Mycobacterium tuberculosis: Cell envelope profiles and interactions with the host.","volume":"13","author":"Schami","year":"2023","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.3390\/pharmaceutics17111459","article-title":"Advanced nanosystems and emerging therapies: Innovations in tuberculosis treatment and drug resistance.","volume":"17","author":"Sharma","year":"2025","journal-title":"Pharmaceutics"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1111\/jam.14478","article-title":"Recent updates on drug resistance in mycobacterium tuberculosis","volume":"128","author":"Singh","year":"2020","journal-title":"J. Appl. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1080\/22221751.2020.1785334","article-title":"Molecular mechanisms of underlying genetic factors and associated mutations for drug resistance in Mycobacterium tuberculosis.","volume":"9","author":"Swain","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.3390\/app10072376","article-title":"Model-informed drug discovery and development strategy for the rapid development of anti-tuberculosis drug combinations.","volume":"10","author":"Van Wijk","year":"2020","journal-title":"Appl. Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s42003-023-04433-w","article-title":"Omics analysis of Mycobacterium tuberculosis isolates uncovers Rv3094c, an ethionamide metabolism-associated gene.","volume":"6","author":"Wan","year":"2023","journal-title":"Commun. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1038\/s42003-024-06006-x","article-title":"Bacteriophage therapy for the treatment of Mycobacterium tuberculosis infections in humanized mice.","volume":"7","author":"Yang","year":"2024","journal-title":"Commun. Biol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1942089\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:41Z","timestamp":1789623101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1942089\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":33,"alternative-id":["10.3389\/fmicb.2026.1942089"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1942089","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1942089"}}