{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T12:41:17Z","timestamp":1782304877635,"version":"3.54.5"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Multidrug-resistant tuberculosis (TB) presents a major public health dilemma. Heteroresistance, the coexistence of drug-resistant and drug-susceptible strains or of multiple drug-resistant strains with discrete haplotypes, may affect accurate diagnosis and the institution of effective treatment. Subculture, or passage of cells onto fresh growth medium, is utilized to preserve\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            cell lines and is universally employed in TB diagnostics. The impact of such passages, typically performed in the absence of drug, on drug-resistant subpopulations is hypothesized to vary according to the competitive costs of genotypic resistance-associated variants. We applied ultradeep next-generation sequencing to 61 phenotypically rifampin-monoresistant (\n            <jats:italic>n<\/jats:italic>\n            = 17) and preextensively (\n            <jats:italic>n<\/jats:italic>\n            = 41) and extensively (\n            <jats:italic>n<\/jats:italic>\n            = 3) drug-resistant isolates with presumptive heteroresistance at two time points in serial subculture. We found significant dynamic loss of minor-variant resistant subpopulations across all analyzed resistance-determining regions, including eight isolates (13%) whose antibiogram data would have transitioned from resistant to susceptible for at least one drug through subculture. Surprisingly, some resistance-associated variants appeared to be selected for in subculture.\n          <\/jats:p>","DOI":"10.1128\/aac.00888-17","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:40:28Z","timestamp":1505176828000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance"],"prefix":"10.1128","volume":"61","author":[{"given":"John Z.","family":"Metcalfe","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Streicher","sequence":"additional","affiliation":[{"name":"DST\/NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Theron","sequence":"additional","affiliation":[{"name":"DST\/NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-2100","authenticated-orcid":false,"given":"Rebecca E.","family":"Colman","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Penaloza","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Allender","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute, Flagstaff, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrin","family":"Lemmer","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute, Flagstaff, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin M.","family":"Warren","sequence":"additional","affiliation":[{"name":"DST\/NRF Centre of Excellence for Biomedical Tuberculosis Research and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Engelthaler","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute, Flagstaff, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(49)91327-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124410"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02741-12"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201703-0556OC"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126626"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05905-11"},{"key":"e_1_3_2_8_2","first-page":"21","article-title":"Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes","volume":"41","author":"Canetti G","year":"1969","unstructured":"Canetti G FoxW KhomenkoA MahlerHT MenonNK MitchisonDA RistN SmelevNA. 1969. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes. Bull World Health Organ41:21\u201343.","journal-title":"Bull World Health Organ"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2016.10.023"},{"key":"e_1_3_2_10_2","unstructured":". 2014. Mycobacteriology laboratory manual. World Health Organization. http:\/\/www.who.int\/tb\/laboratory\/mycobacteriology-laboratory-manual.pdf. Accessed 30 July 2017."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702377104"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.8.1856"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.029199-0"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(00)00340-X"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02775-15"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq102"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2747"},{"key":"e_1_3_2_18_2","unstructured":". World Health Organization Global TB Programme. Updated interim critical concentrations for first-line and second-line DST. http:\/\/www.stoptb.org\/wg\/gli\/assets\/documents\/Updated%20critical%20concentration%20table_1st%20and%202nd%20line%20drugs.pdf. Accessed 1 March 2017."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00888-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00888-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:40:46Z","timestamp":1645476046000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00888-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11]]},"references-count":17,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1128\/AAC.00888-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00888-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11]]},"assertion":[{"value":"2017-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00888-17"}}