Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan
Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-93501-4 |
| _version_ | 1818346979173859328 |
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| author | Anwar Sheed Khan Jody E. Phelan Muhammad Tahir Khan Sajid Ali Muhammad Qasim Gary Napier Susana Campino Sajjad Ahmad Otavio Marques Cabral Shulin Zhang Hazir Rahman Dong-Qing Wei Taane G. Clark Taj Ali Khan |
| author_facet | Anwar Sheed Khan Jody E. Phelan Muhammad Tahir Khan Sajid Ali Muhammad Qasim Gary Napier Susana Campino Sajjad Ahmad Otavio Marques Cabral Shulin Zhang Hazir Rahman Dong-Qing Wei Taane G. Clark Taj Ali Khan |
| author_sort | Anwar Sheed Khan |
| collection | DOAJ |
| description | Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may also be involved. To characterise underlying rifampicin resistance mutations in the TB endemic province of Khyber Pakhtunkhwa, we sequenced 51 M. tuberculosis isolates collected between 2016 and 2019; predominantly, MDR-TB (n = 44; 86.3%) and lineage 3 (n = 30, 58.8%) strains. We found that known mutations in rpoB (e.g. S405L), katG (e.g. S315T), or inhA promoter loci explain the MDR-TB. There were 24 unique mutations in rpoA, rpoB, and rpoC genes, including four previously unreported. Five instances of within-host resistance diversity were observed, where two were a mixture of MDR-TB strains containing mutations in rpoB, katG, and the inhA promoter region, as well as compensatory mutations in rpoC. Heteroresistance was observed in two isolates with a single lineage. Such complexity may reflect the high transmission nature of the Khyber Pakhtunkhwa setting. Our study reinforces the need to apply sequencing approaches to capture the full-extent of MDR-TB genetic diversity, to understand transmission, and to inform TB control activities in the highly endemic setting of Pakistan. |
| first_indexed | 2024-12-13T17:26:52Z |
| format | Article |
| id | doaj.art-641c2d4cd264462fbb84db67d61c18c5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T17:26:52Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-641c2d4cd264462fbb84db67d61c18c52022-12-21T23:37:10ZengNature PortfolioScientific Reports2045-23222021-07-0111111010.1038/s41598-021-93501-4Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, PakistanAnwar Sheed Khan0Jody E. Phelan1Muhammad Tahir Khan2Sajid Ali3Muhammad Qasim4Gary Napier5Susana Campino6Sajjad Ahmad7Otavio Marques Cabral8Shulin Zhang9Hazir Rahman10Dong-Qing Wei11Taane G. Clark12Taj Ali Khan13Department of Microbiology, Kohat University of Science and TechnologyFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineInstitute of Molecular Biology and Biotechnology (IMBB), The University of Lahore. KMProvincial Tuberculosis Reference, Laboratory Hayatabad Medical ComplexDepartment of Microbiology, Kohat University of Science and TechnologyFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineInstitute of Basic Medical Science, Khyber Medical UniversityDepartment of Immunology, Institute of Biomedical Sciences, University of Sao PauloDepartment of Microbiology and Immunology, Shanghai Jiao Tong University School of MedicineDepartment of Microbiology, Abdul Wali Khan UniversityState Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, and Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education, Shanghai Jiao Tong UniversityFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical MedicineInstitute of Basic Medical Science, Khyber Medical UniversityAbstract Tuberculosis (TB), caused by Mycobacterium tuberculosis, is endemic in Pakistan. Resistance to both firstline rifampicin and isoniazid drugs (multidrug-resistant TB; MDR-TB) is hampering disease control. Rifampicin resistance is attributed to rpoB gene mutations, but rpoA and rpoC loci may also be involved. To characterise underlying rifampicin resistance mutations in the TB endemic province of Khyber Pakhtunkhwa, we sequenced 51 M. tuberculosis isolates collected between 2016 and 2019; predominantly, MDR-TB (n = 44; 86.3%) and lineage 3 (n = 30, 58.8%) strains. We found that known mutations in rpoB (e.g. S405L), katG (e.g. S315T), or inhA promoter loci explain the MDR-TB. There were 24 unique mutations in rpoA, rpoB, and rpoC genes, including four previously unreported. Five instances of within-host resistance diversity were observed, where two were a mixture of MDR-TB strains containing mutations in rpoB, katG, and the inhA promoter region, as well as compensatory mutations in rpoC. Heteroresistance was observed in two isolates with a single lineage. Such complexity may reflect the high transmission nature of the Khyber Pakhtunkhwa setting. Our study reinforces the need to apply sequencing approaches to capture the full-extent of MDR-TB genetic diversity, to understand transmission, and to inform TB control activities in the highly endemic setting of Pakistan.https://doi.org/10.1038/s41598-021-93501-4 |
| spellingShingle | Anwar Sheed Khan Jody E. Phelan Muhammad Tahir Khan Sajid Ali Muhammad Qasim Gary Napier Susana Campino Sajjad Ahmad Otavio Marques Cabral Shulin Zhang Hazir Rahman Dong-Qing Wei Taane G. Clark Taj Ali Khan Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan Scientific Reports |
| title | Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan |
| title_full | Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan |
| title_fullStr | Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan |
| title_full_unstemmed | Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan |
| title_short | Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan |
| title_sort | characterization of rifampicin resistant mycobacterium tuberculosis in khyber pakhtunkhwa pakistan |
| url | https://doi.org/10.1038/s41598-021-93501-4 |
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