[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-457022-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-457022-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","whole-genome-sequencing-based-detection-of-extensively-drug-resistant-tuberculosis-from-ethiopia","Whole genome sequencing-based detection of extensively drug-resistant tuberculosis from Ethiopia","","Rapid and accurate identification of extensively drug-resistant tuberculosis is essential for effective intervention, yet early detection remains difficult with existing molecular assays and phenotypic testing. This study uses whole-genome sequencing to detect drug-resistance mutations in pre-XDR-TB and XDR-TB isolates from Ethiopia. It evaluates lineage structure and resistance prediction, reports key resistance and cross-resistance mutations, and compares genomic results with phenotypic drug-susceptibility testing to assess concordance.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/whole-genome-sequencing-based-detection-of-extensively-drug-resistant-tuberculosis-from-ethiopia/457022/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/whole-genome-sequencing-based-detection-of-extensively-drug-resistant-tuberculosis-from-ethiopia/457022.png","ImageObject",300,407,{"name":42,"@type":43},"Rhys","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is rapid detection of extensively drug-resistant tuberculosis critical?","Question",{"text":63,"@type":64},"Rapid and accurate detection enables early treatment initiation and helps reduce transmission. The study frames drug-resistant TB as a major public health challenge requiring timely intervention.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the study identify drug resistance mutations and lineages?",{"text":68,"@type":64},"Whole-genome sequencing generated genomic data, with resistance prediction performed using Tuberculosis Profiler and phylogenetic analysis conducted using IQ-tree. The approach targeted mutations linked to resistance in pre-XDR and XDR strains.",{"name":70,"@type":61,"acceptedAnswer":71},"What resistance mutations and cross-resistance were reported?",{"text":72,"@type":64},"The results highlight fluoroquinolone resistance mutations in gyrA and bedaquiline resistance mutations in atpE and Rv0678. Cross-resistance was observed between bedaquiline and clofazimine, and between delamanid and pretomanid.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},457022,1791095686,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":55,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":117,"preview_page_count":4},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","A Nature Portfolio journal  \n[https://doi.org/10.1038/s43856-025-01271-1](https://doi.org/10.1038/s43856-025-01271-1)  \n\n| Whole genome sequencing-based detection of extensively drug-resistant tuberculosis from Ethiopia\u003Cbr> Check for updates |  |\n| --- | --- |\n| Getu Diriba 1,4 , Hilina Mollalign 1,4 , Abyot Meaza 1, Melak Getu 1, Betselot Zerihun 1, Ayinalem Alemu 1, Biniyam Dagne 1, Yeshiwork Abebaw 1,\u003Cbr>Atsbaha Gebreegziabxier Weldemariam1, Chala Bashea 1, Abraham Ali1, Getachew Seid 1, Muluwork Getahun 1, Michael Hailu1, Amanuel Wondimu1, Tsegaye Getachew 1,\u003Cbr>Andargachew Kumsa2, Taye Letta2, Atlabachew Liaulseged2, NeggaAsamene Abera 1, Zelalem Abate3, Ephrem Alemu1, Feyissa Challa 1, Gemechu Tadesse1, Saro Abdella1, Getachew Tollera1 &\u003Cbr>Mesay Hailu Dangisso1 |  |\n| Abstract | Plain language summary |\n| Background Rapid and accurate detection of extensively drug-resistant tuberculosis is crucial for effective intervention. Next-generation sequencing technologies have been recommended to rapidly and accurately detect resistance to second-line anti-TB drugs. We deployed whole-genome sequencingto detect mutations associated with drug resistance in pre-extensively drug-resistant tuberculosis and extensively drug-resistant tuberculosis strains in Ethiopia.\u003Cbr>Methods This report is part of the routine laboratory-based drug-resistance surveillance in Ethiopia. Among 15 pre-extensively drug-resistant tuberculosis and extensively drugresistant tuberculosis isolates identified during the study period, eleven isolates were retrieved by Whole-genome sequencing. Illumina NextSeq 550 instruments were used to generate genomic data. Lineage and drug-resistance prediction were performed with Tuberculosis Profiler, while phylogeny was conducted by IQ-tree.\u003Cbr>Results Of the genotyped isolates, whole-genome sequencing identifies five extensively drug-resistant tuberculosis and four pre-extensively drug-resistant tuberculosis strains. It detects fluoroquinolone resistance mutations gyrA (Ala90Val, Asp94Tyr, Asp94Gly) . Bedaquiline resistance mutations are found in atpE (Glu61Asp) and Rv0678 (139dupG, 141 and 142dupTC) . Cross-resistance is identified between bedaquiline and clofazimine (n = 4) and delamanid and pretomanid(n = 1). Concordance result is observed between phenotypic drug-susceptibility testing and whole-genome sequencing for eight cases, while three cases are discordant (fluoroquinolones, delamanid, and pretomanid) . Phylogenetic analysis reveals three major lineages: Lineage 4 (Euro-American, n = 6 isolates), Lineage 3 (East African-Indian, n = 3 isolates), and Lineage 1 (Indo-Oceanic, n = 2 isolates) .\u003Cbr>Conclusions Whole-genome sequencing identifies dominant mutations in genes such as gyrA, atpE, and Rv067 that are associated with resistance to second-line anti-tuberculosis drugs. Significant cross-resistance is observed between key second-line drugs, bedaquiline and clofazimine, as well as delamanid and pretomanid. This finding highlights the need for routine genomic surveillance to detect drug resistance early, improve treatment outcomes, and prevent transmission. | Drug-resistant tuberculosis (TB) is becoming harder to treat and cure. Genetic testing is being recommended for finding drug resistance in Mycobacterium, a bacterium that causes TB. Here, we isolated bacteria from patients presenting with TB in Ethiopia and foundthat genetic changes madethe bacteria more resistant to new TB drugs, such as bedaquiline, pretomanid, and linezolid. Some of these genetic changes made the bacteria resistant to more than a single drug. Importantly, some highly drug-resistant TB strains were found in people who had been diagnosed for the first time, suggesting that the drug resistance is being passed from person to person. Our findings highlight the urgent need for genetic monitoring of TB in Ethiopia, which could help detect resistance, improve treatment, and prevent the spread of untreatable TB. |\n\nA full list of affiliations appears at the e","cbCaiaHIv6lGVwPV","https://ap.wps.com/l/cbCaiaHIv6lGVwPV","pdf",881729,"English","# Background\n## Rapid detection of DR-TB and current limitations\n# Methods\n## Whole-genome sequencing workflow and analysis tools\n# Results\n## Identified XDR/pre-XDR strains, resistance mutations, cross-resistance, and concordance\n## Phylogenetic lineage findings\n# Conclusions\n## Value of genomic surveillance for early resistance detection","[{\"question\":\"Why is rapid detection of extensively drug-resistant tuberculosis critical?\",\"answer\":\"Rapid and accurate detection enables early treatment initiation and helps reduce transmission. The study frames drug-resistant TB as a major public health challenge requiring timely intervention.\"},{\"question\":\"How did the study identify drug resistance mutations and lineages?\",\"answer\":\"Whole-genome sequencing generated genomic data, with resistance prediction performed using Tuberculosis Profiler and phylogenetic analysis conducted using IQ-tree. The approach targeted mutations linked to resistance in pre-XDR and XDR strains.\"},{\"question\":\"What resistance mutations and cross-resistance were reported?\",\"answer\":\"The results highlight fluoroquinolone resistance mutations in gyrA and bedaquiline resistance mutations in atpE and Rv0678. Cross-resistance was observed between bedaquiline and clofazimine, and between delamanid and pretomanid.\"}]","Whole genome sequencing-based detection of extensively drug-resistant tuberculosis from Ethiopia | PDF",1790748034]