{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:46:20Z","timestamp":1787870780289,"version":"build-2784847793"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology, Government of India","award":["MDR-TB\/2017\/11"],"award-info":[{"award-number":["MDR-TB\/2017\/11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Uncontrolled transmission of Mycobacterium tuberculosis (M. tuberculosis, MTB) drug resistant strains is a challenge to control efforts of the global tuberculosis program. Due to increasing multi-drug resistant (MDR) cases in Arunachal Pradesh, a northeastern state of India, the tracking and tracing of these resistant MTB strains is crucial for infection control and spread of drug resistance. This study aims to correlate the phenotypic DST, genomic DST (gDST) and phylogenetic analysis of MDR-MTB strains in the region. Of the total 200 samples 22 (11%) patients suspected of MDR-TB and 160 (80%) previously treated MDR-TB cases, 125 (62.5%) were identified as MTB. MGIT-960 SIRE DST detected 71\/125 (56.8%) isolates as MDR\/RR-MTB of which 22 (30.9%) were detected resistant to second-line drugs. Whole-genome sequencing of 65 isolates and their gDST found Ser315Thr mutation in katG (35\/45; 77.8%) and Ser531Leu mutation in rpoB (21\/41; 51.2%) associated with drug resistance. SNP barcoding categorized the dataset with Lineage2 (41; 63.1%) being predominant followed by Lineage3 (10; 15.4%), Lineage1 (8; 12.3%) and Lineage4 (6; 9.2%) respectively. Phylogenetic assignment by cgMLST gave insights of two Beijing sub-lineages viz; 2.2.1 (SNP difference &lt; 19) and 2.2.1.2 (SNP difference &lt; 9) associated with recent ongoing transmission in Arunachal Pradesh. This study provides insights in identifying two virulent Beijing sub-lineages (sub-lineage 2.2.1 and 2.2.1.2) with ongoing transmission of TB drug resistance in Arunachal Pradesh.<\/jats:p>","DOI":"10.3390\/genes13020263","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T01:41:59Z","timestamp":1643420519000},"page":"263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China"],"prefix":"10.3390","volume":"13","author":[{"given":"Shiv kumar Rashmi","family":"Mudliar","sequence":"first","affiliation":[{"name":"Department of Microbiology, All India Institute of Medical Sciences, Bhopal 462020, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umay","family":"Kulsum","sequence":"additional","affiliation":[{"name":"Department of Microbiology, All India Institute of Medical Sciences, Bhopal 462020, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4928-2355","authenticated-orcid":false,"given":"Syed Beenish","family":"Rufai","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada"},{"name":"McGill International TB Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9198-6965","authenticated-orcid":false,"given":"Mika","family":"Umpo","sequence":"additional","affiliation":[{"name":"Tomo Riba Institute of Health & Medical Sciences, Naharlagun 791110, Arunachal Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moi","family":"Nyori","sequence":"additional","affiliation":[{"name":"State TB Cell, Naharlagun 791110, Arunachal Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-9647","authenticated-orcid":false,"given":"Sarman","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, All India Institute of Medical Sciences, Bhopal 462020, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020). Global Tuberculosis Report 2020, World Health Organization."},{"key":"ref_2","unstructured":"National Tuberculosis Elimination Programme (2020). India TB Report 2020, National Tuberculosis Elimination Programme."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S0140-6736(19)31882-3","article-title":"Management of drug-resistant tuberculosis","volume":"394","author":"Lange","year":"2019","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2021022","DOI":"10.4178\/epih.e2021022","article-title":"Controlling the drug-resistant tuberculosis epidemic in India: Challenges and impli-cations","volume":"43","author":"Husain","year":"2021","journal-title":"Epidemiol. Health"},{"key":"ref_5","first-page":"477","article-title":"Early detection of multi-drug resistant tuberculosis in India using GenoType MTBDRplus assay & profile of resistance mutations in Mycobacterium tuberculosis","volume":"140","author":"Singh","year":"2014","journal-title":"Indian J. Med Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1099\/mic.0.27539-0","article-title":"Gene expression diversity among Mycobacterium tuber-culosis clinical isolates","volume":"151","author":"Gao","year":"2005","journal-title":"Microbiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3201\/eid0603.000312","article-title":"Mycobacterium tuberculosis Beijing genotype emerging in Vietnam","volume":"6","author":"Anh","year":"2000","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1172\/JCI11426","article-title":"The nature and consequence of genetic variability within Mycobacterium tuberculosis","volume":"107","author":"Bifani","year":"2001","journal-title":"J. Clin. Invest."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mekonnen, A., Merker, M., Collins, J., Addise, D., Aseffa, A., Petros, B., Ameni, G., and Niemann, S. (2018). Molecular epidemiology and drug resistance patterns of Mycobacterium tuberculosis complex isolates from university students and the local community in Eastern Ethiopia. PLoS ONE, 13.","DOI":"10.1101\/322958"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.tube.2011.11.003","article-title":"Mycobacterium tuberculosis\u2014Heterogeneity revealed through whole genome sequencing","volume":"92","author":"Ford","year":"2012","journal-title":"Tuberculosis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13073-019-0660-8","article-title":"Deciphering drug resistance in Mycobacterium tuberculosis using whole-genome sequencing: Progress, promise, and challenges","volume":"11","author":"Cohen","year":"2019","journal-title":"Genome Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1073\/pnas.0511240103","article-title":"Variable host-pathogen compatibility in Mycobacterium tuberculosis","volume":"103","author":"Gagneux","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1128\/JCM.00567-14","article-title":"Whole-genome-based My-cobacterium tuberculosis surveillance: A standardized, portable, and expandable approach","volume":"5","author":"Kohl","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/JCM.02025-18","article-title":"Phylogenetic Analysis of Mycobacterium tuberculosis Strains in Wales by Use of Core Genome Multilocus Sequence Typing to Analyze Whole-Genome Sequencing Data","volume":"57","author":"Jones","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1128\/JCM.02182-15","article-title":"Performance of Xpert MTB\/RIF Assay in Diagnosis of Pleural Tuberculosis by Use of Pleural Fluid Samples","volume":"53","author":"Rufai","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1365-2672.2009.04218.x","article-title":"Multiplex PCR assay for simultaneous detection and differentiation of Mycobacterium tuberculosis, Mycobacterium avium complexes and other Mycobacterial species directly from clinical specimens","volume":"107","author":"Gopinath","year":"2009","journal-title":"J. Appl. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3389\/fmicb.2019.00309","article-title":"Whole Genome Sequencing of Mycobacterium tuberculosis Clinical Isolates from India Reveals Genetic Heterogeneity and Region-Specific Variations That Might Affect Drug Susceptibility","volume":"10","author":"Advani","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1128\/JCM.05188-11","article-title":"Direct drug susceptibility testing of Mycobacterium tuberculosis for rapid detection of multidrug re-sistance using the Bactec MGIT 960 system: A multicenter study","volume":"50","author":"Siddiqi","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-27299-z","article-title":"Association of gyrA and rrs gene mutations detected by MTBDRsl V1 on Mycobacterium tuberculosis strains of diverse genetic background from India","volume":"8","author":"Rufai","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","unstructured":"World Health Organization (2020). Technical Manual for Drug Susceptibility Testing of Medicines Used in the Treatment of Tuberculosis, World Health Organization."},{"key":"ref_21","first-page":"1","article-title":"Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis","volume":"2013","author":"Kim","year":"2013","journal-title":"Tuberc. Res. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1128\/JCM.43.6.2996-2997.2005","article-title":"Extraction of Mycobacterium tuberculosis DNA: A Question of Containment","volume":"43","author":"Somerville","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Black, P.A., de Vos, M., Louw, G.E., van der Merwe, R.G., Dippenaar, A., Streicher, E.M., Abdallah, A.M., Sampson, S.L., Victor, T.C., and Dolby, T. (2013). Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates. BMC Genom., 16.","DOI":"10.1186\/s12864-015-2067-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6614","DOI":"10.1093\/nar\/gkw569","article-title":"NCBI prokaryotic genome annotation pipeline","volume":"44","author":"Tatusova","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows\u2013Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fgene.2012.00035","article-title":"Using Drosophila melanogaster as a Model for Genotoxic Chemical Mutational Studies with a New Program, SnpSift","volume":"3","author":"Cingolani","year":"2012","journal-title":"Front. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9869","DOI":"10.1073\/pnas.94.18.9869","article-title":"Restricted structural gene polymorphism in the Mycobacterium tuberculosis complex indicates evolutionarily recent global dissemination","volume":"94","author":"Sreevatsan","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"W256","DOI":"10.1093\/nar\/gkz239","article-title":"Interactive Tree of Life (iTOL) v4: Recent updates and new developments","volume":"47","author":"Letunic","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_33","first-page":"e000166","article-title":"chewBBACA: A complete suite for gene-by-gene schema creation and strain identification","volume":"4","author":"Silva","year":"2018","journal-title":"Microb. Genom."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Francisco, A.P., Vaz, C., Monteiro, P.T., Melo-Cristino, J., Ramirez, M., and Carri\u00e7o, J.A. (2012). PHYLOViZ: Phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-87"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e000971","DOI":"10.1136\/bmjgh-2018-000971","article-title":"Drug-resistant tuberculosis: Is India ready for the challenge?","volume":"3","author":"Chatterjee","year":"2018","journal-title":"BMJ Glob. Health"},{"key":"ref_36","first-page":"501","article-title":"Detection of multi-drug resistance & characterization of mutations in Mycobacterium tuberculosis isolates from North- Eastern States of India using GenoType MTBDRplus assay","volume":"140","author":"Singhal","year":"2014","journal-title":"Indian J. Med. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Roetzer, A., Diel, R., Kohl, T.A., R\u00fcckert, C., N\u00fcbel, U., Blom, J., Wirth, T., Jaenicke, S., Schuback, S., and R\u00fcsch-Gerdes, S. (2013). Whole Genome Sequencing versus Traditional Genotyping for Investigation of a Mycobacterium tuberculosis Outbreak: A Longitudinal Molecular Epidemiological Study. PLoS Med., 10.","DOI":"10.1371\/journal.pmed.1001387"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ijid.2021.10.044","article-title":"Genetic Diversity and Transmission of Multidrug-Resistant Mycobacterium tuberculosis strains in Lusaka, Zambia","volume":"114","author":"Chizimu","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4812","DOI":"10.1038\/ncomms5812","article-title":"A robust SNP barcode for typing Mycobacterium tuberculosis complex strains","volume":"5","author":"Coll","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ebiom.2018.07.030","article-title":"Harmonized Genome Wide Typing of Tubercle Bacilli Using a Web-Based Gene-By-Gene Nomenclature System","volume":"34","author":"Kohl","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bergval, I., Sengstake, S., Brankova, N., Levterova, V., Abad\u00eda, E., Tadumaze, N., Bablishvili, N., Akhalaia, M., Tuin, K., and Schuitema, A. (2012). Combined species identification, genotyping, and drug resistance detection of Mycobacterium tuberculosis cultures by MLPA on a bead-based array. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043240"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nieto Ramirez, L.M., Ferro, B.E., Diaz, G., Anthony, R.M., de Beer, J., and van Soolingen, D. (2020). Genetic profiling of Mycobacterium tuberculosis revealed \u201cmodern\u201d Beijing strains linked to MDR-TB from Southwestern Colombia. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0224908"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S197","DOI":"10.1016\/j.ijmyco.2016.07.005","article-title":"Predominance of Beijing lineage among pre-extensively drug-resistant and ex-tensively drug-resistant strains of Mycobacterium tuberculosis: A tertiary care center experience","volume":"5","author":"Rufai","year":"2016","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12879-020-05479-5","article-title":"Detection of Beijing strains of MDR M. tuberculosis and their association with drug resistance mutations in katG, rpoB, and embB genes","volume":"20","author":"Gupta","year":"2020","journal-title":"BMC Infect. Dis."},{"key":"ref_45","first-page":"1","article-title":"The study on the association between Beijing genotype family and drug susceptibility phenotypes of Mycobacterium tuberculosis in Beijing","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijid.2018.06.009","article-title":"Insight into multidrug-resistant Beijing genotype Mycobacterium tuberculosis isolates in Myanmar","volume":"76","author":"San","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/s41588-018-0117-9","article-title":"Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam","volume":"50","author":"Holt","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13718","DOI":"10.1038\/s41598-019-50078-3","article-title":"A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages","volume":"9","author":"Ajawatanawong","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.tube.2011.07.005","article-title":"Mycobacterium tuberculosis Beijing genotype: A template for success","volume":"91","author":"Hanekom","year":"2011","journal-title":"Tuberculosis"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Devi, K.R., Bhutia, R., Bhowmick, S., Mukherjee, K., Mahanta, J., and Narain, K. (2015). Genetic Diversity of Mycobacterium tuberculosis Isolates from Assam, India: Dominance of Beijing Family and Discovery of Two New Clades Related to CAS1_Delhi and EAI Family Based on Spoligotyping and MIRU-VNTR Typing. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145860"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/263\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:10:34Z","timestamp":1760134234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,29]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["genes13020263"],"URL":"https:\/\/doi.org\/10.3390\/genes13020263","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202112.0283.v1","asserted-by":"object"}]},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,29]]}}}