Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana
BackgroundThe emergence of drug-resistant Mycobacterium tuberculosis (M. tb) strains remains a threat to tuberculosis (TB) prevention and care. Understanding the drug resistance profiles of circulating strains is crucial for effective TB control. This study aimed to describe the genetic diversity of...
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2025-02-01
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| author | Tuelo Mogashoa Tuelo Mogashoa Johannes Loubser Ontlametse T. Choga Ontlametse T. Choga Justice Tresor Ngom Wonderful T. Choga Wonderful T. Choga Mpaphi B. Mbulawa Tuduetso Molefi One Stephen Topo Makhondo Kedumetse Seru Patience Motshosi Boitumelo Zuze Joseph Makhema Rosemary M. Musonda Dimpho Otukile Chawangwa Modongo Botshelo T. Kgwaadira Keabetswe Fane Simani Gaseitsiwe Rob M. Warren Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Anzaan Dippenaar Elizabeth M. Streicher |
| author_facet | Tuelo Mogashoa Tuelo Mogashoa Johannes Loubser Ontlametse T. Choga Ontlametse T. Choga Justice Tresor Ngom Wonderful T. Choga Wonderful T. Choga Mpaphi B. Mbulawa Tuduetso Molefi One Stephen Topo Makhondo Kedumetse Seru Patience Motshosi Boitumelo Zuze Joseph Makhema Rosemary M. Musonda Dimpho Otukile Chawangwa Modongo Botshelo T. Kgwaadira Keabetswe Fane Simani Gaseitsiwe Rob M. Warren Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Anzaan Dippenaar Elizabeth M. Streicher |
| author_sort | Tuelo Mogashoa |
| collection | DOAJ |
| description | BackgroundThe emergence of drug-resistant Mycobacterium tuberculosis (M. tb) strains remains a threat to tuberculosis (TB) prevention and care. Understanding the drug resistance profiles of circulating strains is crucial for effective TB control. This study aimed to describe the genetic diversity of rifampicin-resistant M. tb strains circulating in Botswana using whole genome sequencing (WGS).MethodsThis study included 202 stored M. tb isolates from people diagnosed with rifampicin-resistant TB (RR-TB) between January 2016 and June 2023. Genomic DNA was extracted using the cetyltrimethylammonium bromide (CTAB) method. Library preparation was performed using the Illumina DNA prep kit following the manufacturer's instructions. Sequencing was done on Illumina NextSeq2000. TBProfiler software was used to identify known M. tb lineages and drug resistance profiles. Statistical analyses were performed on STATA version 18.ResultsWGS analysis revealed multidrug resistance (57.9%: 95% CI; 50.7–64.8), Pre-XDR (16.8%, 95% CI: 11.9–22.7), RR-TB (20.2%: 95% CI: 14.98–26.5), and HR-TB (0.5%, 95% CI; 0.01–2.7). We identified a high genetic diversity with three predominant lineages: lineage 4 (60.9%, 95% CI; 53.8–67.7), lineage 1 (22.8%: 95% CI; 17.2–29.2), and lineage 2 (13.9%, 95% CI: 9.4–19.4). The most frequently observed drug resistance mutations for rifampicin, isoniazid, ethambutol, streptomycin, pyrazinamide, and fluoroquinolones were rpoB S450L (28.6%), katG S315T (60.5%), embA_c.-29_-28delCT, embB Q497R (31.7%), rrs_n.517C>T (47.1%), pncA_c.375_389delCGATGAGGTCGATGT (36.0%) and gyrA A90V (79.4%), respectively. No bedaquiline and delamanid resistance-associated mutations were detected.ConclusionsThis study highlights the high genetic diversity of M. tb strains, with a predominance of lineage 4 among people with RR-TB in Botswana. It provides valuable insights into the genetic diversity of rifampicin-resistant M. tb strains circulating in Botswana. |
| format | Article |
| id | doaj-art-7c5570f005f84e198815e44d6ba0a4fc |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj-art-7c5570f005f84e198815e44d6ba0a4fc2025-02-11T18:51:01ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-02-011610.3389/fmicb.2025.15351601535160Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in BotswanaTuelo Mogashoa0Tuelo Mogashoa1Johannes Loubser2Ontlametse T. Choga3Ontlametse T. Choga4Justice Tresor Ngom5Wonderful T. Choga6Wonderful T. Choga7Mpaphi B. Mbulawa8Tuduetso Molefi9One Stephen10Topo Makhondo11Kedumetse Seru12Patience Motshosi13Boitumelo Zuze14Joseph Makhema15Rosemary M. Musonda16Dimpho Otukile17Chawangwa Modongo18Botshelo T. Kgwaadira19Keabetswe Fane20Simani Gaseitsiwe21Rob M. Warren22Sikhulile Moyo23Sikhulile Moyo24Sikhulile Moyo25Sikhulile Moyo26Anzaan Dippenaar27Elizabeth M. Streicher28Botswana Harvard Health Partnership, Gaborone, BotswanaSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaBotswana Harvard Health Partnership, Gaborone, BotswanaDepartment of Medical Sciences, University of Botswana, Gaborone, BotswanaSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaBotswana Harvard Health Partnership, Gaborone, BotswanaDepartment of Medical Sciences, University of Botswana, Gaborone, BotswanaBotswana National Tuberculosis Reference Laboratory, Gaborone, BotswanaBotswana National Tuberculosis Program, Ministry of Health, Gaborone, BotswanaBotswana National Tuberculosis Reference Laboratory, Gaborone, BotswanaBotswana National Tuberculosis Program, Ministry of Health, Gaborone, BotswanaBotswana Harvard Health Partnership, Gaborone, BotswanaBotswana Harvard Health Partnership, Gaborone, BotswanaBotswana Harvard Health Partnership, Gaborone, BotswanaBotswana Harvard Health Partnership, Gaborone, BotswanaBotswana Harvard Health Partnership, Gaborone, BotswanaVictus Global Botswana Organization, Gaborone, BotswanaVictus Global Botswana Organization, Gaborone, BotswanaTB/HIV Program, Botswana-University of Maryland School of Medicine, Health Initiative (BUMMHI), Gaborone, BotswanaTB/HIV Program, Botswana-University of Maryland School of Medicine, Health Initiative (BUMMHI), Gaborone, BotswanaBotswana Harvard Health Partnership, Gaborone, BotswanaSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaBotswana Harvard Health Partnership, Gaborone, BotswanaDepartment of Pathology, Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaSchool of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa0Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States1Family Medicine and Population Health, University of Antwerp, Antwerp, BelgiumSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaBackgroundThe emergence of drug-resistant Mycobacterium tuberculosis (M. tb) strains remains a threat to tuberculosis (TB) prevention and care. Understanding the drug resistance profiles of circulating strains is crucial for effective TB control. This study aimed to describe the genetic diversity of rifampicin-resistant M. tb strains circulating in Botswana using whole genome sequencing (WGS).MethodsThis study included 202 stored M. tb isolates from people diagnosed with rifampicin-resistant TB (RR-TB) between January 2016 and June 2023. Genomic DNA was extracted using the cetyltrimethylammonium bromide (CTAB) method. Library preparation was performed using the Illumina DNA prep kit following the manufacturer's instructions. Sequencing was done on Illumina NextSeq2000. TBProfiler software was used to identify known M. tb lineages and drug resistance profiles. Statistical analyses were performed on STATA version 18.ResultsWGS analysis revealed multidrug resistance (57.9%: 95% CI; 50.7–64.8), Pre-XDR (16.8%, 95% CI: 11.9–22.7), RR-TB (20.2%: 95% CI: 14.98–26.5), and HR-TB (0.5%, 95% CI; 0.01–2.7). We identified a high genetic diversity with three predominant lineages: lineage 4 (60.9%, 95% CI; 53.8–67.7), lineage 1 (22.8%: 95% CI; 17.2–29.2), and lineage 2 (13.9%, 95% CI: 9.4–19.4). The most frequently observed drug resistance mutations for rifampicin, isoniazid, ethambutol, streptomycin, pyrazinamide, and fluoroquinolones were rpoB S450L (28.6%), katG S315T (60.5%), embA_c.-29_-28delCT, embB Q497R (31.7%), rrs_n.517C>T (47.1%), pncA_c.375_389delCGATGAGGTCGATGT (36.0%) and gyrA A90V (79.4%), respectively. No bedaquiline and delamanid resistance-associated mutations were detected.ConclusionsThis study highlights the high genetic diversity of M. tb strains, with a predominance of lineage 4 among people with RR-TB in Botswana. It provides valuable insights into the genetic diversity of rifampicin-resistant M. tb strains circulating in Botswana.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1535160/fulltuberculosisBotswanagenetic diversityrifampicin resistancewhole genome sequencing |
| spellingShingle | Tuelo Mogashoa Tuelo Mogashoa Johannes Loubser Ontlametse T. Choga Ontlametse T. Choga Justice Tresor Ngom Wonderful T. Choga Wonderful T. Choga Mpaphi B. Mbulawa Tuduetso Molefi One Stephen Topo Makhondo Kedumetse Seru Patience Motshosi Boitumelo Zuze Joseph Makhema Rosemary M. Musonda Dimpho Otukile Chawangwa Modongo Botshelo T. Kgwaadira Keabetswe Fane Simani Gaseitsiwe Rob M. Warren Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Sikhulile Moyo Anzaan Dippenaar Elizabeth M. Streicher Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana Frontiers in Microbiology tuberculosis Botswana genetic diversity rifampicin resistance whole genome sequencing |
| title | Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana |
| title_full | Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana |
| title_fullStr | Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana |
| title_full_unstemmed | Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana |
| title_short | Whole genomic analysis uncovers high genetic diversity of rifampicin-resistant Mycobacterium tuberculosis strains in Botswana |
| title_sort | whole genomic analysis uncovers high genetic diversity of rifampicin resistant mycobacterium tuberculosis strains in botswana |
| topic | tuberculosis Botswana genetic diversity rifampicin resistance whole genome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1535160/full |
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