Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, Indonesia

Tuberculosis (TB) is caused by Mycobacterium tuberculosis infection. Indonesia is ranked second in the world for TB cases. New anti-TB drugs from groups A and B, such as bedaquiline, clofazimine, and linezolid, have been shown to be effective in curing drug resistance in TB patients, and Indonesia i...

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Main Authors: Andriansjah Rukmana, Cynthia Gozali, Linda Erlina
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:International Journal of Microbiology
Online Access:http://dx.doi.org/10.1155/2024/2037961
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author Andriansjah Rukmana
Cynthia Gozali
Linda Erlina
author_facet Andriansjah Rukmana
Cynthia Gozali
Linda Erlina
author_sort Andriansjah Rukmana
collection DOAJ
description Tuberculosis (TB) is caused by Mycobacterium tuberculosis infection. Indonesia is ranked second in the world for TB cases. New anti-TB drugs from groups A and B, such as bedaquiline, clofazimine, and linezolid, have been shown to be effective in curing drug resistance in TB patients, and Indonesia is already using these drugs to treat patients. However, studies comparing the TB strain types with anti-TB resistance profiles are still relevant to understanding the prevalent strains in the country and their phenotypic characteristics. This study aimed to determine the association between the TB lineage distribution using whole-genome sequencing and bedaquiline, clofazimine, and linezolid phenotypic profile resistance among M. tuberculosisrifampicin-resistant isolates from West Java. M. tuberculosis isolates stock of the Department of Microbiology, Faculty of Medicine, Universitas Indonesia, was tested against bedaquiline, clofazimine, and linezolid using a mycobacteria growth indicator tube liquid culture. All isolates were tested for M. tuberculosis and rifampicin resistance using Xpert MTB/RIF. The DNA genome of M. tuberculosis was freshly extracted from a Löwenstein–Jensen medium culture and then sequenced. The isolates showed phenotypically resistance to bedaquiline, clofazimine, and linezolid at 5%, 0%, and 0%, respectively. We identified gene mutations on phenotypically bedaquiline-resistant strains (2/3), and other mutations also found in phenotypically drug-sensitive strains. Mykrobe analysis showed that most (88.33%) of the isolates could be classified as rifampicin-resistant TB. Using Mykrobe and TB-Profiler to determine the lineage distribution, the isolates were found to belong to lineage 4 (Euro-American; 48.33%), lineage 2 (East Asian/Beijing; 46.67%), and lineage 1 (Indo-Oceanic; 5%). This work underlines the requirement to increase the representation of genotype-phenotype TB data while also highlighting the importance and efficacy of WGS in predicting medication resistance and inferring disease transmission.
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spelling doaj-art-8c801204462a42058bae5f477fe6bfba2025-02-03T01:31:53ZengWileyInternational Journal of Microbiology1687-91982024-01-01202410.1155/2024/2037961Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, IndonesiaAndriansjah Rukmana0Cynthia Gozali1Linda Erlina2Department of MicrobiologyMaster Programme of Biomedical SciencesDepartment of Medical ChemistryTuberculosis (TB) is caused by Mycobacterium tuberculosis infection. Indonesia is ranked second in the world for TB cases. New anti-TB drugs from groups A and B, such as bedaquiline, clofazimine, and linezolid, have been shown to be effective in curing drug resistance in TB patients, and Indonesia is already using these drugs to treat patients. However, studies comparing the TB strain types with anti-TB resistance profiles are still relevant to understanding the prevalent strains in the country and their phenotypic characteristics. This study aimed to determine the association between the TB lineage distribution using whole-genome sequencing and bedaquiline, clofazimine, and linezolid phenotypic profile resistance among M. tuberculosisrifampicin-resistant isolates from West Java. M. tuberculosis isolates stock of the Department of Microbiology, Faculty of Medicine, Universitas Indonesia, was tested against bedaquiline, clofazimine, and linezolid using a mycobacteria growth indicator tube liquid culture. All isolates were tested for M. tuberculosis and rifampicin resistance using Xpert MTB/RIF. The DNA genome of M. tuberculosis was freshly extracted from a Löwenstein–Jensen medium culture and then sequenced. The isolates showed phenotypically resistance to bedaquiline, clofazimine, and linezolid at 5%, 0%, and 0%, respectively. We identified gene mutations on phenotypically bedaquiline-resistant strains (2/3), and other mutations also found in phenotypically drug-sensitive strains. Mykrobe analysis showed that most (88.33%) of the isolates could be classified as rifampicin-resistant TB. Using Mykrobe and TB-Profiler to determine the lineage distribution, the isolates were found to belong to lineage 4 (Euro-American; 48.33%), lineage 2 (East Asian/Beijing; 46.67%), and lineage 1 (Indo-Oceanic; 5%). This work underlines the requirement to increase the representation of genotype-phenotype TB data while also highlighting the importance and efficacy of WGS in predicting medication resistance and inferring disease transmission.http://dx.doi.org/10.1155/2024/2037961
spellingShingle Andriansjah Rukmana
Cynthia Gozali
Linda Erlina
Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, Indonesia
International Journal of Microbiology
title Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, Indonesia
title_full Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, Indonesia
title_fullStr Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, Indonesia
title_full_unstemmed Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, Indonesia
title_short Mycobacterium tuberculosis Lineage Distribution Using Whole-Genome Sequencing and Bedaquiline, Clofazimine, and Linezolid Phenotypic Profiles among Rifampicin-Resistant Isolates from West Java, Indonesia
title_sort mycobacterium tuberculosis lineage distribution using whole genome sequencing and bedaquiline clofazimine and linezolid phenotypic profiles among rifampicin resistant isolates from west java indonesia
url http://dx.doi.org/10.1155/2024/2037961
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