{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:32:51Z","timestamp":1790472771759,"version":"4.1.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Mycobacterium tuberculosis<\/jats:italic> drug resistance poses a major threat to tuberculosis control. Current phenotypic tests for drug susceptibility are time-consuming, technically complex, and expensive. Whole genome sequencing is a promising alternative, though the impact of different drug resistance mutations on the minimum inhibitory concentration (MIC) remains to be investigated. We examined the genomes of 72 phenotypically drug-resistant <jats:italic>Mycobacterium tuberculosis<\/jats:italic> isolates from 72 Romanian patients for drug resistance mutations. MICs for first- and second-line drugs were determined using the MycoTB microdilution method. These MICs were compared to macrodilution critical concentration testing by the Mycobacterium Growth Indicator Tube (MGIT) platform and correlated to drug resistance mutations. Sixty-three (87.5%) isolates harboured drug resistance mutations; 48 (66.7%) were genotypically multidrug-resistant. Different drug resistance mutations were associated with different MIC ranges; <jats:italic>katG<\/jats:italic> S315T for isoniazid, and <jats:italic>rpoB<\/jats:italic> S450L for rifampicin were associated with high MICs. However, several mutations such as in <jats:italic>rpoB<\/jats:italic>, <jats:italic>rrs<\/jats:italic> and <jats:italic>rpsL<\/jats:italic>, or <jats:italic>embB<\/jats:italic> were associated with MIC ranges including the critical concentration for rifampicin, aminoglycosides or ethambutol, respectively. Different resistance mutations lead to distinct MICs, some of which may still be overcome by increased dosing. Whole genome sequencing can aid in the timely diagnosis of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> drug resistance and guide clinical decision-making.<\/jats:p>","DOI":"10.1038\/s41598-018-27962-5","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T09:25:24Z","timestamp":1529486724000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Linking minimum inhibitory concentrations to whole genome sequence-predicted drug resistance in Mycobacterium tuberculosis strains from Romania"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3440-1828","authenticated-orcid":false,"given":"Carolien","family":"Ruesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca Lelia","family":"Riza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Florescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidya","family":"Chaidir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Editoiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Aalders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos","family":"Nicolosu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Grecu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Ioana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinout","family":"van Crevel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0581-2003","authenticated-orcid":false,"given":"Jakko","family":"van Ingen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,6,26]]},"reference":[{"key":"27962_CR1","unstructured":"WHO. Global tuberculosis report 2016."},{"key":"27962_CR2","unstructured":"WHO. Multidrug and extensively drug-resistant TB (M\/XDR-TB): 2010 global report on surveillance and response, http:\/\/apps.who.int\/iris\/bitstream\/10665\/44286\/1\/9789241599191_eng.pdf."},{"key":"27962_CR3","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1128\/JCM.02724-12","volume":"51","author":"DJ Horne","year":"2013","unstructured":"Horne, D. J. et al. Diagnostic accuracy and reproducibility of WHO-endorsed phenotypic drug susceptibility testing methods for first-line and second-line antituberculosis drugs. J Clin Microbiol 51, 393\u2013401, https:\/\/doi.org\/10.1128\/JCM.02724-12 (2013).","journal-title":"J Clin Microbiol"},{"key":"27962_CR4","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.cmi.2016.10.022","volume":"23","author":"T Schon","year":"2017","unstructured":"Schon, T. et al. Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives. Clin Microbiol Infect 23, 154\u2013160, https:\/\/doi.org\/10.1016\/j.cmi.2016.10.022 (2017).","journal-title":"Clin Microbiol Infect"},{"key":"27962_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD009593.pub3","author":"KR Steingart","year":"2014","unstructured":"Steingart, K. R. et al. Xpert(R) MTB\/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev, CD009593. https:\/\/doi.org\/10.1002\/14651858.CD009593.pub3 (2014).","journal-title":"Cochrane Database Syst Rev, CD009593"},{"key":"27962_CR6","doi-asserted-by":"publisher","unstructured":"Theron, G. et al. The diagnostic accuracy of the GenoType((R)) MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs. Cochrane Database Syst Rev, CD010705, https:\/\/doi.org\/10.1002\/14651858.CD010705.pub2 (2014).","DOI":"10.1002\/14651858.CD010705.pub2"},{"key":"27962_CR7","unstructured":"WHO. Review of the National Tuberculosis Programme in Romania, 10\u201321 March 2014 (2015)."},{"key":"27962_CR8","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1007\/s10096-011-1382-z","volume":"31","author":"MM Abuali","year":"2012","unstructured":"Abuali, M. M., Katariwala, R. & LaBombardi, V. J. A comparison of the Sensititre(R) MYCOTB panel and the agar proportion method for the susceptibility testing of Mycobacterium tuberculosis. Eur J Clin Microbiol Infect Dis 31, 835\u2013839, https:\/\/doi.org\/10.1007\/s10096-011-1382-z (2012).","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"27962_CR9","doi-asserted-by":"publisher","first-page":"3732","DOI":"10.1128\/JCM.02048-12","volume":"50","author":"L Hall","year":"2012","unstructured":"Hall, L. et al. Evaluation of the Sensititre MycoTB plate for susceptibility testing of the Mycobacterium tuberculosis complex against first- and second-line agents. J Clin Microbiol 50, 3732\u20133734, https:\/\/doi.org\/10.1128\/JCM.02048-12 (2012).","journal-title":"J Clin Microbiol"},{"key":"27962_CR10","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20, 1297\u20131303, https:\/\/doi.org\/10.1101\/gr.107524.110 (2010).","journal-title":"Genome Res"},{"key":"27962_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-015-0164-0","volume":"7","author":"F Coll","year":"2015","unstructured":"Coll, F. et al. Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences. Genome Med 7, 51, https:\/\/doi.org\/10.1186\/s13073-015-0164-0 (2015).","journal-title":"Genome Med"},{"key":"27962_CR12","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.tube.2014.02.005","volume":"94","author":"F Coll","year":"2014","unstructured":"Coll, F. et al. PolyTB: a genomic variation map for Mycobacterium tuberculosis. Tuberculosis (Edinb) 94, 346\u2013354, https:\/\/doi.org\/10.1016\/j.tube.2014.02.005 (2014).","journal-title":"Tuberculosis (Edinb)"},{"key":"27962_CR13","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1128\/JCM.00025-15","volume":"53","author":"S Feuerriegel","year":"2015","unstructured":"Feuerriegel, S. et al. PhyResSE: a Web Tool Delineating Mycobacterium tuberculosis Antibiotic Resistance and Lineage from Whole-Genome Sequencing Data. J Clin Microbiol 53, 1908\u20131914, https:\/\/doi.org\/10.1128\/JCM.00025-15 (2015).","journal-title":"J Clin Microbiol"},{"key":"27962_CR14","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.cmi.2016.09.006","volume":"23","author":"E Andre","year":"2017","unstructured":"Andre, E. et al. Consensus numbering system for the rifampicin resistance-associated rpoB gene mutations in pathogenic mycobacteria. Clin Microbiol Infect 23, 167\u2013172, https:\/\/doi.org\/10.1016\/j.cmi.2016.09.006 (2017).","journal-title":"Clin Microbiol Infect"},{"key":"27962_CR15","doi-asserted-by":"crossref","unstructured":"Barrick, J. E. Identifying structural variation in haploid microbial genomes from short-read resequencing data using breseq. BMC Genomics (2014).","DOI":"10.1186\/1471-2164-15-1039"},{"key":"27962_CR16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1093\/sysbio\/syq010","volume":"59","author":"S Guindon","year":"2010","unstructured":"Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 59, 307\u2013321, https:\/\/doi.org\/10.1093\/sysbio\/syq010 (2010).","journal-title":"Syst Biol"},{"key":"27962_CR17","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1128\/JCM.02378-13","volume":"52","author":"S Banu","year":"2014","unstructured":"Banu, S. et al. Discordance across several methods for drug susceptibility testing of drug-resistant Mycobacterium tuberculosis isolates in a single laboratory. J Clin Microbiol 52, 156\u2013163, https:\/\/doi.org\/10.1128\/JCM.02378-13 (2014).","journal-title":"J Clin Microbiol"},{"key":"27962_CR18","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1128\/AAC.04438-14","volume":"59","author":"AZ Reeves","year":"2015","unstructured":"Reeves, A. Z., Campbell, P. J., Willby, M. J. & Posey, J. E. Disparities in capreomycin resistance levels associated with the rrs A1401G mutation in clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 59, 444\u2013449, https:\/\/doi.org\/10.1128\/AAC.04438-14 (2015).","journal-title":"Antimicrob Agents Chemother"},{"key":"27962_CR19","doi-asserted-by":"publisher","unstructured":"Miotto, P. et al. A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis. Eur Respir J 50, https:\/\/doi.org\/10.1183\/13993003.01354-2017 (2017).","DOI":"10.1183\/13993003.01354-2017"},{"key":"27962_CR20","doi-asserted-by":"publisher","first-page":"78","DOI":"10.4046\/trd.2015.78.2.78","volume":"78","author":"SK Heysell","year":"2015","unstructured":"Heysell, S. K., Moore, J. L., Peloquin, C. A., Ashkin, D. & Houpt, E. R. Outcomes and use of therapeutic drug monitoring in multidrug-resistant tuberculosis patients treated in virginia, 2009\u20132014. Tuberc Respir Dis (Seoul) 78, 78\u201384, https:\/\/doi.org\/10.4046\/trd.2015.78.2.78 (2015).","journal-title":"Tuberc Respir Dis (Seoul)"},{"key":"27962_CR21","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S2213-2600(15)00466-X","volume":"4","author":"LJ Pankhurst","year":"2016","unstructured":"Pankhurst, L. J. et al. Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study. The Lancet Respiratory Medicine 4, 49\u201358, https:\/\/doi.org\/10.1016\/s2213-2600(15)00466-x (2016).","journal-title":"The Lancet Respiratory Medicine"},{"key":"27962_CR22","doi-asserted-by":"publisher","first-page":"7104","DOI":"10.1128\/AAC.01117-15","volume":"59","author":"SK Heysell","year":"2015","unstructured":"Heysell, S. K. et al. Sensititre MycoTB plate compared to Bactec MGIT 960 for first- and second-line antituberculosis drug susceptibility testing in Tanzania: a call to operationalize MICs. Antimicrob Agents Chemother 59, 7104\u20137108, https:\/\/doi.org\/10.1128\/AAC.01117-15 (2015).","journal-title":"Antimicrob Agents Chemother"},{"key":"27962_CR23","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1128\/AAC.01209-13","volume":"58","author":"J Lee","year":"2014","unstructured":"Lee, J. et al. Sensititre MYCOTB MIC plate for testing Mycobacterium tuberculosis susceptibility to first- and second-line drugs. Antimicrob Agents Chemother 58, 11\u201318, https:\/\/doi.org\/10.1128\/AAC.01209-13 (2014).","journal-title":"Antimicrob Agents Chemother"},{"key":"27962_CR24","doi-asserted-by":"publisher","first-page":"329","DOI":"10.5588\/ijtld.15.0573","volume":"20","author":"X Yu","year":"2016","unstructured":"Yu, X. et al. Sensititre(R) MYCOTB MIC plate for drug susceptibility testing of Mycobacterium tuberculosis complex isolates. Int J Tuberc Lung Dis 20, 329\u2013334, https:\/\/doi.org\/10.5588\/ijtld.15.0573 (2016).","journal-title":"Int J Tuberc Lung Dis"},{"key":"27962_CR25","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.5588\/ijtld.15.0896","volume":"20","author":"S Foongladda","year":"2016","unstructured":"Foongladda, S. et al. Comparison of TaqMan((R)) Array Card and MYCOTB(TM) with conventional phenotypic susceptibility testing in MDR-TB. Int J Tuberc Lung Dis 20, 1105\u20131112, https:\/\/doi.org\/10.5588\/ijtld.15.0896 (2016).","journal-title":"Int J Tuberc Lung Dis"},{"key":"27962_CR26","doi-asserted-by":"publisher","first-page":"24","DOI":"10.5588\/ijtld.15.0221","volume":"20","author":"J Dominguez","year":"2016","unstructured":"Dominguez, J. et al. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET\/RESIST-TB consensus statement. Int J Tuberc Lung Dis 20, 24\u201342, https:\/\/doi.org\/10.5588\/ijtld.15.0221 (2016).","journal-title":"Int J Tuberc Lung Dis"},{"issue":"Suppl 3","key":"27962_CR27","doi-asserted-by":"publisher","first-page":"S96","DOI":"10.1093\/infdis\/jiu610","volume":"211","author":"T Gumbo","year":"2015","unstructured":"Gumbo, T., Angulo-Barturen, I. & Ferrer-Bazaga, S. Pharmacokinetic-pharmacodynamic and dose-response relationships of antituberculosis drugs: recommendations and standards for industry and academia. J Infect Dis 211(Suppl 3), S96\u2013S106, https:\/\/doi.org\/10.1093\/infdis\/jiu610 (2015).","journal-title":"J Infect Dis"},{"key":"27962_CR28","doi-asserted-by":"publisher","first-page":"693","DOI":"10.2471\/BLT.11.096644","volume":"90","author":"K Angeby","year":"2012","unstructured":"Angeby, K., Jureen, P., Kahlmeter, G., Hoffner, S. E. & Schon, T. Challenging a dogma: antimicrobial susceptibility testing breakpoints for Mycobacterium tuberculosis. Bull World Health Organ 90, 693\u2013698, https:\/\/doi.org\/10.2471\/BLT.11.096644 (2012).","journal-title":"Bull World Health Organ"},{"key":"27962_CR29","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1093\/jac\/dkv145","volume":"70","author":"G Kahlmeter","year":"2015","unstructured":"Kahlmeter, G. The 2014 Garrod Lecture: EUCAST - are we heading towards international agreement? J Antimicrob Chemother 70, 2427\u20132439, https:\/\/doi.org\/10.1093\/jac\/dkv145 (2015).","journal-title":"J Antimicrob Chemother"},{"key":"27962_CR30","doi-asserted-by":"publisher","unstructured":"Quan, T. P. et al. Evaluation of Whole-Genome Sequencing for Mycobacterial Species Identification and Drug Susceptibility Testing in a Clinical Setting: a Large-Scale Prospective Assessment of Performance against Line Probe Assays and Phenotyping. J Clin Microbiol 56, https:\/\/doi.org\/10.1128\/JCM.01480-17 (2018).","DOI":"10.1128\/JCM.01480-17"},{"key":"27962_CR31","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1128\/JCM.00298-17","volume":"55","author":"J Shea","year":"2017","unstructured":"Shea, J. et al. Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State. J Clin Microbiol 55, 1871\u20131882, https:\/\/doi.org\/10.1128\/JCM.00298-17 (2017).","journal-title":"J Clin Microbiol"},{"key":"27962_CR32","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01550-17","author":"J Heyckendorf","year":"2017","unstructured":"Heyckendorf, J. et al. What is resistance? Impact of phenotypic versus molecular drug resistance testing on multi- and extensively drug-resistant tuberculosis therapy. Antimicrob Agents Chemother. https:\/\/doi.org\/10.1128\/AAC.01550-17 (2017).","journal-title":"Antimicrob Agents Chemother"},{"key":"27962_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10063","volume":"6","author":"P Bradley","year":"2015","unstructured":"Bradley, P. et al. Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. Nat Commun 6, 10063, https:\/\/doi.org\/10.1038\/ncomms10063 (2015).","journal-title":"Nat Commun"},{"key":"27962_CR34","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1128\/AAC.06460-11","volume":"56","author":"L Fenner","year":"2012","unstructured":"Fenner, L. et al. Effect of mutation and genetic background on drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 56, 3047\u20133053, https:\/\/doi.org\/10.1128\/AAC.06460-11 (2012).","journal-title":"Antimicrob Agents Chemother"},{"key":"27962_CR35","doi-asserted-by":"publisher","first-page":"6080","DOI":"10.1128\/AAC.01641-12","volume":"56","author":"CU Koser","year":"2012","unstructured":"Koser, C. U., Feuerriegel, S., Summers, D. K., Archer, J. A. & Niemann, S. Importance of the genetic diversity within the Mycobacterium tuberculosis complex for the development of novel antibiotics and diagnostic tests of drug resistance. Antimicrob Agents Chemother 56, 6080\u20136087, https:\/\/doi.org\/10.1128\/AAC.01641-12 (2012).","journal-title":"Antimicrob Agents Chemother"},{"key":"27962_CR36","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1128\/JCM.00560-14","volume":"52","author":"S Cheng","year":"2014","unstructured":"Cheng, S., Cui, Z., Li, Y. & Hu, Z. Diagnostic accuracy of a molecular drug susceptibility testing method for the antituberculosis drug ethambutol: a systematic review and meta-analysis. J Clin Microbiol 52, 2913\u20132924, https:\/\/doi.org\/10.1128\/JCM.00560-14 (2014).","journal-title":"J Clin Microbiol"},{"key":"27962_CR37","doi-asserted-by":"publisher","first-page":"216","DOI":"10.5588\/ijtld.11.0178","volume":"16","author":"DA Williamson","year":"2012","unstructured":"Williamson, D. A. et al. Clinical failures associated with rpoB mutations in phenotypically occult multidrug-resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis 16, 216\u2013220, https:\/\/doi.org\/10.5588\/ijtld.11.0178 (2012).","journal-title":"Int J Tuberc Lung Dis"},{"key":"27962_CR38","doi-asserted-by":"publisher","first-page":"2915","DOI":"10.1093\/jac\/dkt284","volume":"68","author":"J Ho","year":"2013","unstructured":"Ho, J., Jelfs, P. & Sintchencko, V. Phenotypically occult multidrug-resistant Mycobacterium tuberculosis: dilemmas in diagnosis and treatment. J Antimicrob Chemother 68, 2915\u20132920, https:\/\/doi.org\/10.1093\/jac\/dkt284 (2013).","journal-title":"J Antimicrob Chemother"},{"key":"27962_CR39","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.1128\/AAC.00007-10","volume":"55","author":"C Plinke","year":"2011","unstructured":"Plinke, C., Walter, K., Aly, S., Ehlers, S. & Niemann, S. Mycobacterium tuberculosis embB codon 306 mutations confer moderately increased resistance to ethambutol in vitro and in vivo. Antimicrob Agents Chemother 55, 2891\u20132896, https:\/\/doi.org\/10.1128\/AAC.00007-10 (2011).","journal-title":"Antimicrob Agents Chemother"},{"key":"27962_CR40","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0598-2","volume":"14","author":"AA Witney","year":"2016","unstructured":"Witney, A. A. et al. Clinical use of whole genome sequencing for Mycobacterium tuberculosis. BMC Med 14, 46, https:\/\/doi.org\/10.1186\/s12916-016-0598-2 (2016).","journal-title":"BMC Med"},{"key":"27962_CR41","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1128\/JCM.00691-14","volume":"52","author":"FB Jamieson","year":"2014","unstructured":"Jamieson, F. B. et al. Profiling of rpoB mutations and MICs for rifampin and rifabutin in Mycobacterium tuberculosis. J Clin Microbiol 52, 2157\u20132162, https:\/\/doi.org\/10.1128\/JCM.00691-14 (2014).","journal-title":"J Clin Microbiol"},{"key":"27962_CR42","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s12041-017-0805-8","volume":"96","author":"CC Naidoo","year":"2017","unstructured":"Naidoo, C. C. & Pillay, M. Fitness-compensatory mutations facilitate the spread of drug-resistant F15\/LAM4\/KZN and F28 Mycobacterium tuberculosis strains in KwaZulu-Natal, South Africa. Journal of Genetics 96, 599\u2013612, https:\/\/doi.org\/10.1007\/s12041-017-0805-8 (2017).","journal-title":"Journal of Genetics"},{"key":"27962_CR43","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1093\/jac\/dkt150","volume":"68","author":"T Schon","year":"2013","unstructured":"Schon, T. et al. Rifampicin-resistant and rifabutin-susceptible Mycobacterium tuberculosis strains: a breakpoint artefact? J Antimicrob Chemother 68, 2074\u20132077, https:\/\/doi.org\/10.1093\/jac\/dkt150 (2013).","journal-title":"J Antimicrob Chemother"},{"key":"27962_CR44","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1128\/JCM.02741-12","volume":"51","author":"L Rigouts","year":"2013","unstructured":"Rigouts, L. et al. Rifampin resistance missed in automated liquid culture system for Mycobacterium tuberculosis isolates with specific rpoB mutations. J Clin Microbiol 51, 2641\u20132645, https:\/\/doi.org\/10.1128\/JCM.02741-12 (2013).","journal-title":"J Clin Microbiol"},{"key":"27962_CR45","doi-asserted-by":"crossref","unstructured":"De Beer, J. L. et al. Molecular surveillance of multi- and extensively drug-resistant tuberculosis transmission in the European Union from 2003 to 2011. Euro Surveill 19 (2014).","DOI":"10.2807\/1560-7917.ES2014.19.11.20742"},{"key":"27962_CR46","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1099\/jmm.0.000534","volume":"66","author":"RM Burke","year":"2017","unstructured":"Burke, R. M., Coronel, J. & Moore, D. Minimum inhibitory concentration distributions for first- and second-line antimicrobials against Mycobacterium tuberculosis. J Med Microbiol 66, 1023\u20131026, https:\/\/doi.org\/10.1099\/jmm.0.000534 (2017).","journal-title":"J Med Microbiol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27962-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27962-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27962-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T06:45:35Z","timestamp":1671605135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-27962-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,26]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["27962"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-27962-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,26]]},"assertion":[{"value":"19 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9676"}}