{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:32:43Z","timestamp":1761514363629,"version":"3.37.3"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST104-2325-B-404-001","MOST105-2325-B-404-001","MOST104-2325-B-404-001","MOST104-2325-B-404-001","MOST105-2325-B-404-001"],"award-info":[{"award-number":["MOST104-2325-B-404-001","MOST105-2325-B-404-001","MOST104-2325-B-404-001","MOST104-2325-B-404-001","MOST105-2325-B-404-001"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare, Taiwan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug-resistant tuberculosis (TB) is a global crisis and a threat to health security. Since conventional drug susceptibility testing (DST) takes several weeks, we herein described a molecular assay to rapidly identify multidrug-resistant (MDR) and extensively drug-resistant (XDR) and reveal transmission associated-mutations of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> complex (MTBC) isolates in 6 to 7\u2009hours. An array was designed with 12 pairs of primers and 60 single nucleotide polymorphisms of 9 genes: <jats:italic>rpoB<\/jats:italic>, <jats:italic>katG<\/jats:italic>, <jats:italic>inhA<\/jats:italic>, <jats:italic>ahpC<\/jats:italic>, <jats:italic>embB<\/jats:italic>, <jats:italic>rpsL<\/jats:italic>, <jats:italic>gyrA<\/jats:italic>, <jats:italic>rrs<\/jats:italic> and <jats:italic>eis<\/jats:italic>. We assessed the performance of the array using 176 clinical MTBC isolates. The results of culture-based DST were used as the gold standard, the GenoType MTBDR<jats:italic>plus<\/jats:italic> and MTBDR<jats:italic>sl<\/jats:italic> tests were used for parallel comparison, and gene sequencing was performed to resolve the discordance. The sensitivities and specificities of the array are comparable to those of the MTBDR<jats:italic>plus<\/jats:italic> test for resistance to isoniazid (INH) (100.0%, 96.7%) and rifampicin (RIF) (99.4%, 96.7%) and of the MTBDR<jats:italic>sl<\/jats:italic> test for resistance to fluoroquinolones (FQs) (100%, 100%) and second-line injectable drugs (SLIDs) (98.3%, 100%). The sensitivities of the array for detecting resistance to ethambutol and streptomycin were 79.3% and 64.9%, respectively. The array has potential as a powerful tool for clinical diagnosis and epidemiological investigations.<\/jats:p>","DOI":"10.1038\/s41598-019-39339-3","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T12:06:06Z","timestamp":1552565166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis"],"prefix":"10.1038","volume":"9","author":[{"given":"Ching-Yu","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jui-Yun","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Hui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Chun","family":"Yen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Han","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung Chain","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruwen","family":"Jou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"39339_CR1","unstructured":"World Health Organization. Global tuberculosis report 2018. World Health Organization, Geneva, Switzerland. WHO\/HTM\/TB\/2018 (2018)."},{"key":"39339_CR2","unstructured":"World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis (Update 2016). World Health Organization, Geneva, Switherland. WHO\/HTM\/TB\/2016.04 (2016)."},{"key":"39339_CR3","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1128\/JCM.02499-08","volume":"47","author":"W-L Huang","year":"2009","unstructured":"Huang, W.-L., Chen, H.-Y., Kuo, Y.-M. & Jou, R. Performance assessment of the GenoType MTBDRplus test and DNA sequencing in detection of multidrug-resistant Mycobacterium tuberculosis. J. Clin. Microbiol. 47, 2520\u20132524 (2009).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR4","doi-asserted-by":"publisher","unstructured":"Theron, G. et al. The diagnostic accuracy of the GenoType\u00ae MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs. Cochrane Database Syst. Rev. 4\u2013123, https:\/\/doi.org\/10.1002\/14651858.CD010705.pub2 (2014).","DOI":"10.1002\/14651858.CD010705.pub2"},{"key":"39339_CR5","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.1128\/JCM.01257-15","volume":"53","author":"E Tagliani","year":"2015","unstructured":"Tagliani, E. et al. Diagnostic performance of the new version (v2.0) of GenoType MTBDRsl assay for detection of resistance to fluoroquinolones and second-line injectable drugs: a multicenter study. J. Clin. Microbiol. 53, 2961\u20132969 (2015).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR6","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1128\/JCM.00051-16","volume":"54","author":"F Brossier","year":"2016","unstructured":"Brossier, F. et al. Performance of the new version (v2.0) of the GenoType MTBDRsl test for detection of resistance to second-line drugs in multidrug-resistant Mycobacterium tuberculosis complex strains. J. Clin. Microbiol. 54, 1573\u20131580 (2016).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR7","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.tube.2016.09.006","volume":"101","author":"J Kostera","year":"2016","unstructured":"Kostera, J. et al. Analytical and clinical performance characteristics of the Abbott RealTime MTB RIF\/INH Resistance, an assay for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis in pulmonary specimens. Tuberculosis 101, 137\u2013143 (2016).","journal-title":"Tuberculosis"},{"key":"39339_CR8","doi-asserted-by":"publisher","first-page":"115","DOI":"10.5145\/ACM.2014.17.4.115","volume":"17","author":"JH Lee","year":"2014","unstructured":"Lee, J. H., Kim, B. H. & Lee, M.-K. Performance evaluation of anyplex plus MTB\/NTM and MDR-TB detection kit for detection of Mycobacteria and for anti-tuberculosis drug susceptibility test. Ann. Clin. Microbiol. 17, 115\u2013122 (2014).","journal-title":"Ann. Clin. Microbiol."},{"key":"39339_CR9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.tube.2004.01.002","volume":"84","author":"PD Butcher","year":"2004","unstructured":"Butcher, P. D. Microarrays for Mycobacterium tuberculosis. Tuberculosis 84, 131\u2013137 (2004).","journal-title":"Tuberculosis"},{"key":"39339_CR10","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.diagmicrobio.2013.01.009","volume":"75","author":"P-L Lu","year":"2013","unstructured":"Lu, P.-L. et al. Evaluation of a membrane array for detection of Mycobacterium tuberculosis complex and nontuberculous mycobacteria in positive liquid cultures. Diagn. Microbiol. Infect. Dis. 75, 337\u2013341 (2013).","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"39339_CR11","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1128\/JCM.01862-12","volume":"50","author":"M-R Lee","year":"2012","unstructured":"Lee, M.-R. et al. Performance assessment of the DR. TBDR\/NTM IVD kit for direct detection of Mycobacterium tuberculosis isolates, including fifampin-resistant isolates, and nontuberculous mycobacteria. J. Clin. Microbiol. 50, 3398\u20133401 (2012).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR12","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1093\/jac\/dkl058","volume":"57","author":"LM Arag\u00f3n","year":"2006","unstructured":"Arag\u00f3n, L. M. et al. Rapid detection of specific gene mutations associated with isoniazid or rifampicin resistance in Mycobacterium tuberculosis clinical isolates using non-fluorescent low-density DNA microarrays. J. Antimicrob. Chemother. 57, 825\u2013831 (2006).","journal-title":"J. Antimicrob. Chemother."},{"key":"39339_CR13","doi-asserted-by":"publisher","first-page":"2378","DOI":"10.1128\/JCM.00439-06","volume":"44","author":"JC Caoili","year":"2006","unstructured":"Caoili, J. C. et al. Evaluation of the TB-biochip oligonucleotide microarray system for rapid detection of rifampin resistance in Mycobacterium tuberculosis. J. Clin. Microbiol. 44, 2378\u20132381 (2006).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR14","doi-asserted-by":"publisher","first-page":"4850","DOI":"10.1128\/JCM.42.10.4850-4852.2004","volume":"42","author":"J-Y Deng","year":"2004","unstructured":"Deng, J.-Y. et al. Multiplex detection of mutations in clinical isolates of rifampin-resistant Mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. J. Clin. Microbiol. 42, 4850\u20134852 (2004).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR15","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1099\/jmm.0.46129-0","volume":"54","author":"S Denkin","year":"2005","unstructured":"Denkin, S., Volokhov, D., Chizhikov, V. & Zhang, Y. Microarray-based pncA genotyping of pyrazinamide-resistant strains of Mycobacterium tuberculosis. J. Med. Microbiol. 54, 1127\u20131131 (2005).","journal-title":"J. Med. Microbiol."},{"key":"39339_CR16","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/j.1469-0691.2005.01183.x","volume":"11","author":"D Gryadunov","year":"2005","unstructured":"Gryadunov, D. et al. Evaluation of hybridisation on oligonucleotide microarrays for analysis of drug-resistant Mycobacterium tuberculosis. Clin. Microbiol. Infect. 11, 531\u2013539 (2005).","journal-title":"Clin. Microbiol. Infect."},{"key":"39339_CR17","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3164\/jcbn.2008033","volume":"42","author":"Y Shimizu","year":"2008","unstructured":"Shimizu, Y. et al. Five-antituberculosis drug-resistance genes detection using array system. J. Clin. Biochem. Nutr. 42, 228\u2013234 (2008).","journal-title":"J. Clin. Biochem. Nutr."},{"key":"39339_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-13-240","volume":"13","author":"DV Zimenkov","year":"2013","unstructured":"Zimenkov, D. V. et al. Detection of second-line drug resistance in Mycobacterium tuberculosis using oligonucleotide microarrays. BMC Infect. Dis. 13, 240 (2013).","journal-title":"BMC Infect. Dis."},{"key":"39339_CR19","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.diagmicrobio.2005.09.014","volume":"54","author":"S-Y Kim","year":"2006","unstructured":"Kim, S.-Y. et al. Evaluation of the CombiChip MycobacteriaTM Drug-Resistance detection DNA chip for identifying mutations associated with resistance to isoniazid and rifampin in Mycobacterium tuberculosis. Diagn. Microbiol. Infect. Dis. 54, 203\u2013210 (2006).","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"39339_CR20","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.diagmicrobio.2004.01.001","volume":"49","author":"MM Wade","year":"2004","unstructured":"Wade, M. M., Volokhov, D., Peredelchuk, M., Chizhikov, V. & Zhang, Y. Accurate mapping of mutations of pyrazinamide-resistant Mycobacterium tuberculosis strains with a scanning-frame oligonucleotide microarray. Diagn. Microbiol. Infect. Dis. 49, 89\u201397 (2004).","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"39339_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-12-303","volume":"12","author":"Z Zhang","year":"2012","unstructured":"Zhang, Z. et al. Rapid and accurate detection of RMP- and INH- resistant Mycobacterium tuberculosis in spinal tuberculosis specimens by CapitalBioTM DNA microarray: A prospective validation study. BMC Infect. Dis. 12, 303 (2012).","journal-title":"BMC Infect. Dis."},{"key":"39339_CR22","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s10096-012-1798-0","volume":"32","author":"EV Kurbatova","year":"2013","unstructured":"Kurbatova, E. V. et al. Performance of Cepheid\u00ae Xpert MTB\/RIF\u00ae and TB Biochip\u00ae MDR in two regions of Russia with a high prevalence of drug-resistant tuberculosis. Eur. J. Clin. Microbiol. Infect. Dis. 32, 735\u2013743 (2013).","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"39339_CR23","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1093\/jac\/dkt448","volume":"69","author":"R Moure","year":"2014","unstructured":"Moure, R. et al. Characterization of the embB gene in Mycobacterium tuberculosis isolates from Barcelona and rapid detection of main mutations related to ethambutol resistance using a low-density DNA array. J. Antimicrob. Chemother. 69, 947\u2013954 (2014).","journal-title":"J. Antimicrob. Chemother."},{"key":"39339_CR24","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1093\/jac\/dkw015","volume":"71","author":"DV Zimenkov","year":"2016","unstructured":"Zimenkov, D. V., Kulagina, E. V., Antonova, O. V., Zhuravlev, V. Y. & Gryadunov, D. A. Simultaneous drug resistance detection and genotyping of Mycobacterium tuberculosis using a low-density hydrogel microarray. J. Antimicrob. Chemother. 71, 1520\u20131531 (2016).","journal-title":"J. Antimicrob. Chemother."},{"key":"39339_CR25","doi-asserted-by":"publisher","first-page":"O542","DOI":"10.1111\/1469-0691.12517","volume":"20","author":"W-L Huang","year":"2014","unstructured":"Huang, W.-L., Hsu, Z.-J., Chang, T. C. & Jou, R. Rapid and accurate detection of rifampin and isoniazid-resistant Mycobacterium tuberculosis using an oligonucleotide array. Clin. Microbiol. Infect. 20, O542\u2013O549 (2014).","journal-title":"Clin. Microbiol. Infect."},{"key":"39339_CR26","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1128\/JCM.00251-16","volume":"54","author":"RR Nathavitharana","year":"2016","unstructured":"Nathavitharana, R. R. et al. Multicenter noninferiority evaluation of Hain GenoType MTBDRplus version 2 and Nipro NTM\u2009+\u2009MDRTB line probe assays for detection of rifampin and isoniazid resistance. J. Clin. Microbiol. 54, 1624\u20131630 (2016).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR27","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.jinf.2014.09.010","volume":"70","author":"B Molina-Moya","year":"2015","unstructured":"Molina-Moya, B. et al. AID TB resistance line probe assay for rapid detection of resistant Mycobacterium tuberculosis in clinical samples. J. Infect. 70, 400\u2013408 (2015).","journal-title":"J. Infect."},{"key":"39339_CR28","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1128\/JCM.00521-07","volume":"45","author":"D Hillemann","year":"2007","unstructured":"Hillemann, D., R\u00fcsch-Gerdes, S. & Richter, E. Evaluation of the GenoType MTBDRplus assay for rifampin and isoniazid susceptibility testing of Mycobacterium tuberculosis strains and clinical specimens. J. Clin. Microbiol. 45, 2635\u20132640 (2007).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR29","doi-asserted-by":"publisher","first-page":"e00812","DOI":"10.1128\/mBio.00812-17","volume":"8","author":"S Chakravorty","year":"2017","unstructured":"Chakravorty, S. et al. The new Xpert MTB\/RIF Ultra: improving detection of Mycobacterium tuberculosis and resistance to rifampin in an assay suitable for point-of-care testing. MBio. 8, e00812\u201300817 (2017).","journal-title":"MBio."},{"key":"39339_CR30","doi-asserted-by":"publisher","first-page":"4435","DOI":"10.1128\/JCM.40.12.4435-4438.2002","volume":"40","author":"C Cavusoglu","year":"2002","unstructured":"Cavusoglu, C., Hilmioglu, S., Guneri, S. & Bilgic, A. Characterization of rpoB mutations in rifampin-resistant clinical isolates of Mycobacterium tuberculosis from Turkey by DNA sequencing and line probe assay. J. Clin. Microbiol. 40, 4435\u20134438 (2002).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR31","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1128\/JCM.39.1.107-110.2001","volume":"39","author":"M Heep","year":"2001","unstructured":"Heep, M. et al. Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. J. Clin. Microbiol. 39, 107\u2013110 (2001).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR32","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/j.1574-6968.1996.tb08515.x","volume":"144","author":"H Taniguchi","year":"1996","unstructured":"Taniguchi, H. et al. Rifampicin resistance and mutation of the rpoB gene in Mycobacterium tuberculosis. FEMS Microbiol. Lett. 144, 103\u2013108 (1996).","journal-title":"FEMS Microbiol. Lett."},{"key":"39339_CR33","doi-asserted-by":"publisher","first-page":"3409","DOI":"10.1128\/JCM.00515-06","volume":"44","author":"X Ma","year":"2006","unstructured":"Ma, X. et al. rpoB Gene Mutations and molecular characterization of rifampin-resistant Mycobacterium tuberculosis isolates from Shandong province, China. J. Clin. Microbiol. 44, 3409\u20133412 (2006).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR34","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 (2014).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR35","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1093\/jac\/dkt090","volume":"68","author":"D Machado","year":"2013","unstructured":"Machado, D. et al. High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations. J. Antimicrob. Chemother. 68, 1728\u20131732 (2013).","journal-title":"J. Antimicrob. Chemother."},{"key":"39339_CR36","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1128\/AAC.01288-09","volume":"54","author":"H Safi","year":"2010","unstructured":"Safi, H. et al. Allelic Exchange and mutant selection demonstrate that common clinical embCAB gene mutations only modestly increase resistance to ethambutol in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 54, 103\u2013108 (2010).","journal-title":"Antimicrob. Agents Chemother."},{"key":"39339_CR37","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/1471-2180-12-90","volume":"12","author":"S Feuerriegel","year":"2012","unstructured":"Feuerriegel, S. et al. Sequence analysis for detection of first-line drug resistance in Mycobacterium tuberculosis strains from a high-incidence setting. BMC Microbiol. 12, 90 (2012).","journal-title":"BMC Microbiol."},{"key":"39339_CR38","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.tube.2013.07.001","volume":"93","author":"R Moure","year":"2013","unstructured":"Moure, R. et al. Detection of streptomycin and quinolone resistance in Mycobacterium tuberculosis by a low-density DNA array. Tuberculosis 93, 508\u2013514 (2013).","journal-title":"Tuberculosis"},{"key":"39339_CR39","doi-asserted-by":"crossref","unstructured":"Lee, A. S. G., Ong, D. C. T., Wong, J. C. L., Siu, G. K. H. & Yam, W.-C. High-resolution melting analysis for the rapid detection of fluoroquinolone and streptomycin resistance in Mycobacterium tuberculosis. Plos One 7 (2012).","DOI":"10.1371\/journal.pone.0031934"},{"key":"39339_CR40","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1054\/tuld.1998.0002","volume":"79","author":"S Ramaswamy","year":"1998","unstructured":"Ramaswamy, S. & Musser, J. M. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber. Lung Dis. Off. J. Int. Union Tuberc. Lung Dis. 79, 3\u201329 (1998).","journal-title":"Tuber. Lung Dis. Off. J. Int. Union Tuberc. Lung Dis."},{"key":"39339_CR41","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1128\/AAC.01814-10","volume":"55","author":"SY Wong","year":"2011","unstructured":"Wong, S. Y. et al. Mutations in gidB Confer low-level streptomycin resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 55, 2515\u20132522 (2011).","journal-title":"Antimicrob. Agents Chemother."},{"key":"39339_CR42","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1111\/j.1365-2958.2006.05585.x","volume":"63","author":"S Okamoto","year":"2007","unstructured":"Okamoto, S. et al. Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria. Mol. Microbiol. 63, 1096\u20131106 (2007).","journal-title":"Mol. Microbiol."},{"key":"39339_CR43","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1093\/jac\/dks033","volume":"67","author":"FA Sirgel","year":"2012","unstructured":"Sirgel, F. A. et al. gyrA mutations and phenotypic susceptibility levels to ofloxacin and moxifloxacin in clinical isolates of Mycobacterium tuberculosis. J. Antimicrob. Chemother. 67, 1088\u20131093 (2012).","journal-title":"J. Antimicrob. Chemother."},{"key":"39339_CR44","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1128\/AAC.49.2.571-577.2005","volume":"49","author":"CE Maus","year":"2005","unstructured":"Maus, C. E., Plikaytis, B. B. & Shinnick, T. M. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 49, 571\u2013577 (2005).","journal-title":"Antimicrob. Agents Chemother."},{"key":"39339_CR45","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1111\/j.1365-2958.2010.07218.x","volume":"77","author":"D Shcherbakov","year":"2010","unstructured":"Shcherbakov, D. et al. Directed mutagenesis of Mycobacterium smegmatis 16S rRNA to reconstruct the in vivo evolution of aminoglycoside resistance in Mycobacterium tuberculosis. Mol. Microbiol. 77, 830\u2013840 (2010).","journal-title":"Mol. Microbiol."},{"key":"39339_CR46","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1089\/mdr.2011.0063","volume":"18","author":"FA Sirgel","year":"2011","unstructured":"Sirgel, F. A. et al. Mutations in the rrs A1401G gene and phenotypic resistance to amikacin and capreomycin in Mycobacterium tuberculosis. Microb. Drug Resist. 18, 193\u2013197 (2011).","journal-title":"Microb. Drug Resist."},{"key":"39339_CR47","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1128\/AAC.42.5.1295","volume":"42","author":"GJ Alangaden","year":"1998","unstructured":"Alangaden, G. J. et al. Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 42, 1295\u20131297 (1998).","journal-title":"Antimicrob. Agents Chemother."},{"key":"39339_CR48","doi-asserted-by":"publisher","first-page":"5064","DOI":"10.1128\/AAC.00851-09","volume":"53","author":"L Jugheli","year":"2009","unstructured":"Jugheli, L. et al. High level of cross-resistance between kanamycin, amikacin, and capreomycin among Mycobacterium tuberculosis isolates from Georgia and a close relation with mutations in the rrs gene. Antimicrob. Agents Chemother. 53, 5064\u20135068 (2009).","journal-title":"Antimicrob. Agents Chemother."},{"key":"39339_CR49","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1093\/jac\/dks178","volume":"67","author":"MB Gikalo","year":"2012","unstructured":"Gikalo, M. B., Nosova, E. Y., Krylova, L. Y. & Moroz, A. M. The role of eis mutations in the development of kanamycin resistance in Mycobacterium tuberculosis isolates from the Moscow region. J. Antimicrob. Chemother. 67, 2107\u20132109 (2012).","journal-title":"J. Antimicrob. Chemother."},{"key":"39339_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijmyco.2015.09.001","volume":"5","author":"P Kambli","year":"2016","unstructured":"Kambli, P. et al. Correlating rrs and eis promoter mutations in clinical isolates of Mycobacterium tuberculosis with phenotypic susceptibility levels to the second line injectables. Int. J. Mycobacteriology 5, 1\u20136 (2016).","journal-title":"Int. J. Mycobacteriology"},{"key":"39339_CR51","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1164\/rccm.201103-0536OC","volume":"184","author":"R Blakemore","year":"2011","unstructured":"Blakemore, R. et al. A multisite assessment of the quantitative capabilities of the Xpert MTB\/RIF assay. Am. J. Respir. Crit. Care Med. 184, 1076\u20131084 (2011).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"39339_CR52","doi-asserted-by":"publisher","first-page":"8950","DOI":"10.1002\/anie.201004475","volume":"49","author":"J Grimes","year":"2010","unstructured":"Grimes, J., Gerasimova, Y. V. & Kolpashchikov, D. M. Real-time SNP analysis in secondary structure-folded nucleic acids. Angew. Chem. Int. Ed Engl. 49, 8950\u20138953 (2010).","journal-title":"Angew. Chem. Int. Ed Engl."},{"key":"39339_CR53","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1128\/JCM.01144-16","volume":"54","author":"S Hofmann-Thiel","year":"2016","unstructured":"Hofmann-Thiel, S., Molodtsov, N., Antonenka, U. & Hoffmann, H. Evaluation of the Abbott RealTime MTB and RealTime MTB INH\/RIF assays for direct detection of Mycobacterium tuberculosis complex and resistance markers in respiratory and extrapulmonary specimens. J. Clin. Microbiol. 54, 3022\u20133027 (2016).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR54","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1128\/JCM.01904-15","volume":"54","author":"M Sali","year":"2016","unstructured":"Sali, M. et al. Multicenter evaluation of Anyplex Plus MTB\/NTM MDR-TB assay for rapid detection of Mycobacterium tuberculosis complex and multidrug-resistant isolates in pulmonary and extrapulmonary specimens. J. Clin. Microbiol. 54, 59\u201363 (2016).","journal-title":"J. Clin. Microbiol."},{"key":"39339_CR55","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.5588\/ijtld.13.0095","volume":"17","author":"HW Choi","year":"2013","unstructured":"Choi, H. W., Miele, K., Dowdy, D. & Shah, M. Cost-effectiveness of Xpert\u00ae MTB\/RIF for diagnosing pulmonary tuberculosis in the United States. Int. J. Tuberc. Lung Dis. Off. J. Int. Union Tuberc. Lung Dis. 17, 1328\u20131335 (2013).","journal-title":"Int. J. Tuberc. Lung Dis. Off. J. Int. Union Tuberc. Lung Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-39339-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-39339-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-39339-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T07:36:13Z","timestamp":1671262573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-39339-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,14]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["39339"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-39339-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2019,3,14]]},"assertion":[{"value":"25 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2019","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":"4425"}}