{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:04:42Z","timestamp":1789607082571,"version":"build-2803163510"},"reference-count":70,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI152110"],"award-info":[{"award-number":["R01AI152110"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Tropical Med Int Health"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tuberculosis remains a major public health threat globally, with drug\u2010resistant strains undermining treatment efficacy. We analyzed 126\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    <\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>M. tuberculosis<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) isolates with diverse drug resistance spectra and selected 35 for whole genome sequencing (WGS) using Illumina NextSeq, SMRT PacBio Onso and SMRT PacBio Revio sequencing platforms. The study aimed to characterize drug resistance profiles, compare short\u2010 and long\u2010read sequencing performance, identify lineages among South African isolates, detect known drug resistance mutations and their lineage\u2010specific patterns, and utilize long\u2010read SMRT platforms for epigenetic profiling. Multiple drug resistance mutations were identified, some lineage\u2010specific, and notably, East\u2010African\u2010Indian (EAI) Lineage 1 isolates often considered less pathogenic, showed significant potential for multidrug\u2010resistance development, including higher fluoroquinolone resistance as compared to other lineages. Three DNA motifs with methylated adenines, namely CACGCaG, CtCCaG and GaTNNNNRtAC, were detected, with methylation patterns varying by lineage and strain due to mutations in the corresponding methyltransferases (MTases). A particularly notable finding was the stable maintenance of a genetic heterogeneity in the\n                    <jats:italic>mamB<\/jats:italic>\n                    MTase, performing methylation at CACGC\n                    <jats:italic>a<\/jats:italic>\n                    G motifs. These results highlight the combined role of genetic and epigenetic variation in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>M. tuberculosis<\/jats:italic>\n                    <\/jats:styled-content>\n                    adaptive evolution and underscore the value of integrating long\u2010read sequencing into TB surveillance and research.\n                  <\/jats:p>","DOI":"10.1111\/tmi.70228","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:31:42Z","timestamp":1789605102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patterns of Drug Resistance, Drug Resistance Conferring Mutations and Genomic\n                    <scp>DNA<\/scp>\n                    Methylation Revealed in\n                    <scp>\n                      <i>Mycobacterium tuberculosis<\/i>\n                    <\/scp>\n                    From South Africa"],"prefix":"10.1111","author":[{"given":"Unarine","family":"Matodzi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Genetics and Microbiology Centre for Bioinformatics and Computational Biology, University of Pretoria  Pretoria South Africa"},{"name":"South African Medical Research Council\u2010Office of AIDS and TB  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0369-5728","authenticated-orcid":false,"given":"Awelani","family":"Mutshembele","sequence":"additional","affiliation":[{"name":"South African Medical Research Council\u2010Office of AIDS and TB  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Mensah","sequence":"additional","affiliation":[{"name":"Department of Microbiological Pathology, Tuberculosis Research Unit Sefako Makgatho Health Sciences University  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dillon","family":"Muzondiwa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Genetics and Microbiology Centre for Bioinformatics and Computational Biology, University of Pretoria  Pretoria South Africa"},{"name":"Department of Microbiology, Faculty of Science Stellenbosch University  Stellenbosch South Africa"},{"name":"The School for Data Science and Computational Thinking, Stellenbosch University  Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ndivhuho A.","family":"Makhado","sequence":"additional","affiliation":[{"name":"Department of Microbiological Pathology, Tuberculosis Research Unit Sefako Makgatho Health Sciences University  Pretoria South Africa"},{"name":"Basic and Translational Sciences, Africa Health Research Institute  Durban South Africa"},{"name":"Department of Medical Microbiology National Health Laboratory Service, Dr George Mukhari Tertiary Laboratory  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg N.","family":"Reva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Genetics and Microbiology Centre for Bioinformatics and Computational Biology, University of Pretoria  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2018.00417","article-title":"Virulence of \n                     Mycobacterium tuberculosis\n                   Clinical Isolates Is Associated With Sputum Pre\u2010Treatment Bacterial Load, Lineage, Survival in Macrophages, and Cytokine Response","volume":"8","author":"Tram T. 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B.","year":"2018","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"issue":"4","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.3390\/antibiotics10040423","article-title":"Bibliometric Analysis on Tuberculosis and Tuberculosis\u2010Related Research Trends in Africa: A Decade\u2010Long Study","volume":"10","author":"Igwaran A.","year":"2021","journal-title":"Antibiotics"},{"key":"e_1_2_10_4_1","unstructured":"World Health Organization \u201cGlobal Tuberculosis Report 2024 \u201d(Geneva: 2024) https:\/\/www.who.int\/teams\/global\u2010programme\u2010on\u2010tuberculosis\u2010and\u2010lung\u2010health\/tb\u2010reports\/global\u2010tuberculosis\u2010report\u20102024."},{"issue":"4","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1010893","article-title":"Back\u2010To\u2010Africa Introductions of \n                     Mycobacterium tuberculosis\n                   as the Main Cause of Tuberculosis in Dar Es Salaam, Tanzania","volume":"19","author":"Zwyer M.","year":"2023","journal-title":"PLoS Pathogens"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","unstructured":"M.Zwyer Z. 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L.","year":"2025","journal-title":"PLOS Global Public Health"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13073-021-00953-4","article-title":"GenTB: A User\u2010Friendly Genome\u2010Based Predictor for Tuberculosis Resistance Powered by Machine Learning","volume":"13","author":"Gr\u00f6schel M. I.","year":"2021","journal-title":"Genome Medicine"},{"key":"e_1_2_10_18_1","first-page":"79","article-title":"Clade\u2010Specific Distribution of Antibiotic Resistance Mutations in the Population of \n                     Mycobacterium tuberculosis\n                  . 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