Comparative whole genome analysis of Mycobacterium tuberculosis isolated from BPaLM and individualized regimen treated patients at Dr. Soetomo Hospital, Indonesia
Abstract
Background: The World Health Organization (WHO) recommends whole genome sequencing (WGS) to support the detection of drug-resistant tuberculosis and the use of the new regimen BPaLM (Bedaquiline-Pretomanid-Linezolid-Moxifloxacin) to treat drug-resistant tuberculosis (TB). Genomic profiles of Mycobacterium tuberculosis (MTB) are needed to understand the regimen's future impact comprehensively.
Methods: In this study, we performed WGS to Mycobacterium tuberculosis isolates from rifampicin resistant tuberculosis patients at Dr. Soetomo Hospital. A total of 15 samples consisting of 14 clinical isolate samples (8 BPaLM and 6 Individualized treated patients) and one laboratory H37Rv reference strain were sequenced using the Illumina MiSeq platform and analyzed using Galaxy, TBProfiler, Mykrobe, and ResFinder.
Results: Lineage analysis revealed that L2.2 was the predominant strain (48%), followed by L4, L4.3, L2.1, and L1.2. Most rifampicin-resistant and multidrug-resistant strains were associated with the East Asian Beijing lineage, with a smaller proportion linked to Euro-American lineages. The TBProfiler and Mykrobe demonstrated higher sensitivity than ResFinder (86% versus 79%), while all tools showed high specificity. Resistance associated mutations were primarily identified in rpoB, katG, embB, and pncA, with single nucleotide variants being the most common. This study has a limited number of representative clinical isolates, thus representing further study with a greater…
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