Pan-genomic analysis of the multi-drug resistant strains of Mycobacterium tuberculosis

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains one of the most critical infectious diseases worldwide. The emergence of multi-drug resistant tuberculosis (MDR-TB) continues to pose a significant challenge to effective treatment and disease control. This study aims to perform a pan-genome analysis of MDR-TB isolates from three eastern Indian states namely Arunachal Pradesh, Odisha and Sikkim to analyze the regional genomic diversity, identify the antibiotic resistance genes prevalent within these populations and functionally characterize the accessory genes present.Whole-genome sequencing (WGS) datasets retrieved from public repositories were processed and analyzed using a bioinformatics pipeline comprising FastQC, Trimmomatic, Unicycler, Prokka, Roary, PanGP, RAxML, Phandango, TB-Profiler and eggNOG mapper. The analysis classified genes into core and accessory genomes and evaluated the openness of the pan-genome isolates from the three regions using Heaps' and power law model. The results indicated that MDR-TB pan-genome remains open across all three states suggesting ongoing gene diversity. The investigation of resistance genes enabled the identification of prevalent resistance patterns among the eastern Indian isolates. Functional annotation and KEGG pathway mapping of accessory genes and hypothetical proteins were carried out to understand their biological roles and identify potential targets for drug development.