Comparative whole genome analysis of Mycobacterium tuberculosis isolated from BPaLM and individualized regimen treated patients at Dr. Soetomo Hospital, Indonesia.

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 number of population sample of both groups.

CONCLUSIONS

Beijing lineage strains predominated and were associated with increased drug resistance. Variants in efflux regulatory genes may contribute to the emergence of multidrug-resistant strains. The Mann-Whitney U test revealed no statistically significant difference between the two groups, with a p-value of 0.4136 (p > 0.05). Furthermore, genomic analysis revealed that the BPALM group exhibited a lower burden of single nucleotide polymorphisms (SNPs) and fewer unique cumulative genetic variants than the Individualized treatment group.