{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:13Z","timestamp":1785432493555,"version":"3.56.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470011, 82170007"],"award-info":[{"award-number":["82470011, 82170007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n To characterize the mutation profile of the\n ahpC<\/jats:italic>\n gene in isoniazid resistance (INH\n r<\/jats:sup>\n )\n Mycobacterium tuberculosis<\/jats:italic>\n (MTB) isolates and to evaluate the correlation between specific mutations and resistance levels, a total of 1,337 INH\n r<\/jats:sup>\n MTB isolates were collected through the Chinese Drug Resistance Surveillance Program (2013\u20132020). The minimum inhibitory concentrations (MICs) for INH, rifampicin (RIF), and ethionamide were determined by broth microdilution, followed by whole-genome sequencing analysis. Among 1,337 INH\n r<\/jats:sup>\n -<\/jats:italic>\n MTB isolates, 45.5% (608\/1,337) were multidrug-resistant (MDR), and 54.5% (729\/1,337) were RIF-sensitive cases, with lineage 2 predominating (1,013\/1,337, 75.8%). Resistance mutations were identified in 79.1% (1,058\/1,337) of strains, primarily\n katG<\/jats:italic>\n Ser315Thr (65.5%, 695\/1,058) and\n inhA<\/jats:italic>\n C-777T (19.7%, 208\/1,058). Notably, 5.3% (56\/1,058) isolates harbored standalone\n ahpC<\/jats:italic>\n mutations, with 83.3% (5\/6) C-81T, 60.0% (9\/15) G-48A, 57.1% (4\/7) C-54T, 50.0% (3\/6) C-57T, and 42.1% (8\/19) C-52T mutations showing high-level INH resistance. Accordingly, 91.7% (11\/12) dual\n katG<\/jats:italic>\n 315<\/jats:sup>\n +\n inhA<\/jats:italic>\n mutations conferred high-level INH resistance, while\n ahpC<\/jats:italic>\n C-57T mutants universally exhibited MDR. The\n ahpC<\/jats:italic>\n mutations are associated with high-level INH resistance in variants without concurrent\n katG<\/jats:italic>\n or\n inhA<\/jats:italic>\n mutations. This finding significantly advances our understanding of tuberculosis resistance profiling, enabling more comprehensive detection of INH\n r<\/jats:sup>\n -MTB and optimizing therapeutic strategies.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Among INH-resistant MTB clinical isolates, mutations in the\n ahpC<\/jats:italic>\n promoter region have been considered to occur in combination with other mutations, such as\n katG<\/jats:italic>\n and\n inhA<\/jats:italic>\n , in a compensatory role. While the\n ahpC<\/jats:italic>\n mutations have been incorporated into the World Health Organization (WHO)-recommended rapid diagnostic test, Xpert MTB\/extensively drug-resistant tuberculosis (XDR), it has been still ambiguous about the standalone effects on INH resistance spectrum. Our findings demonstrate that the\n ahpC<\/jats:italic>\n mutations are associated with high-level INH resistance in variants without concurrent\n katG<\/jats:italic>\n or\n inhA<\/jats:italic>\n mutations. This finding significantly advances our understanding of TB resistance profiling, enabling a more comprehensive detection of INH\n r<\/jats:sup>\n -MTB and optimizing therapeutic strategies.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.02496-25","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:16:22Z","timestamp":1773965782000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence and resistance spectrum of\n ahpC<\/i>\n mutations in isoniazid-resistant\n Mycobacterium tuberculosis<\/i>\n isolates"],"prefix":"10.1128","volume":"14","author":[{"given":"Xiaomeng","family":"Wu","sequence":"first","affiliation":[{"name":"Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feina","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical University, Beijing Key Laboratory of Core Technologies for the Prevention and Treatment of Emerging Infectious Diseases in Children, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Center for Children\u2019s Health","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xia","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for Tuberculosis Control and Prevention, Chinese Centre for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children\u2019s Hospital, Capital Medical 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