Whole genome sequencing reveals novel resistance-conferring mutations and large genome deletions in drug-resistant Mycobacterium tuberculosis isolates from Indonesia

•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia.•Large genome deletions conferring isoniazid resistance were also identified.•Pre-existing mutations resistant to new and repurposed oral drugs were not detected. This study evaluated drug resistance profiles of...

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Published in:Journal of Global Antimicrobial Resistance Vol. 44; pp. 314 - 318
Main Authors: Aung, Htin Lin, Chaidir, Lidya, Pitaloka, Dian Ayu Eka, Miyahara, Yugen, Kumar, Narender, Soeroto, Arto Yuwono, Cook, Greg M, van Crevel, Reinout, Alisjahbana, Bachti, Peacock, Sharon J., Hill, Philip C
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01.09.2025
Elsevier
Subjects:
Antitubercular Agents - pharmacology
Bacterial Proteins - genetics
Catalase - genetics
Drug Resistance, Multiple, Bacterial - genetics
GeneXpert
Genome, Bacterial
Humans
Indonesia
Infectious Disease
Isoniazid - pharmacology
MDR-TB
Microbial Sensitivity Tests
Mutation
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - isolation & purification
Novel mutations
Rifampin - pharmacology
Sequence Deletion
Tuberculosis
Tuberculosis, Multidrug-Resistant - microbiology
WGS
Whole Genome Sequencing
Indonesia
WGS
Tuberculosis
Whole genome sequencing
Novel mutations
MDR-TB
GeneXpert
Indonesia
ISSN:2213-7165, 2213-7173, 2213-7165, 2213-7173
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Summary:•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia.•Large genome deletions conferring isoniazid resistance were also identified.•Pre-existing mutations resistant to new and repurposed oral drugs were not detected. This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches. We performed phenotypic drug-susceptibility testing (DST), coupled with whole-genome sequencing (WGS) of 142 Mtb isolates identified as RIF-R (Rifampicin resistant) using the Xpert MTB/RIF platform. We found 107/142 (75%) isolates had high-level isoniazid resistance (INH-R) and rifampicin resistance (RIF-R). Of 107 isolates, we found two had novel katG mutations and three had large genome deletions encompassing the katG gene conferring INH-R. We also did not detect pre-existing mutations resistant to new and repurposed oral drugs bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD). Known drug-resistance conferring mutations reported in this study can be detected by the newly launched Xpert MTB/XDR together with Xpert MTB/RIF, providing clinicians with an expanded drug-susceptibility report without the need for culturing and WGS. On the other hand,the novel mutations and deletions found in this study are escaping routine diagnostics and could drive outbreaks of MDR-TB in Indonesia. The mass rollout of new and repurposed drugs for the treatment of drug-resistant TB in Indonesia is reassured by the absence of pre-existing mutations in this study. However, tools for rapid detection of resistance to these new drugs are urgently required to circumvent treatment-emergent resistance.
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ISSN:2213-7165
2213-7173
2213-7165
2213-7173
DOI:10.1016/j.jgar.2025.07.017