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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/641c2d4cd264462fbb84db67d61c18c5
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spelling	oai:doaj.org-article:641c2d4cd264462fbb84db67d61c18c52021-12-02T15:39:50ZCharacterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan10.1038/s41598-021-93501-42045-2322https://doaj.org/article/641c2d4cd264462fbb84db67d61c18c52021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93501-4https://doaj.org/toc/2045-2322Abstract 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.Anwar Sheed KhanJody E. PhelanMuhammad Tahir KhanSajid AliMuhammad QasimGary NapierSusana CampinoSajjad AhmadOtavio Marques CabralShulin ZhangHazir RahmanDong-Qing WeiTaane G. ClarkTaj Ali KhanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan
title_short	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_sort	characterization of rifampicin-resistant mycobacterium tuberculosis in khyber pakhtunkhwa, pakistan
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/641c2d4cd264462fbb84db67d61c18c5
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Characterization of rifampicin-resistant Mycobacterium tuberculosis in Khyber Pakhtunkhwa, Pakistan

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