Global whole-genome–based genomic insights into Mycobacterium tuberculosis: Clonal dominance, sequence-type structure, and antimicrobial resistance-virulence landscapes

BACKGROUND: Tuberculosis (TB) remains a major global public health burden, exacerbated by the continued emergence and spread of drug-resistant Mycobacterium tuberculosis. Despite the rapid expansion of publicly available whole-genome sequencing data, gaps remain in the consistent characterization of global population structure, dominant sequence-type (ST) distributions, accessory genome variability, and antimicrobial resistance (AMR) gene profiles, largely due to fragmented and uneven sampling across regions and time periods. This study aimed to conduct a large-scale in silico analysis of publicly available M. tuberculosis whole-genome sequences to descriptively characterize global ST structure, accessory genome diversity, AMR gene landscapes, and their geographic and temporal distributions, while integrating available phenotypic susceptibility data. METHODS: We conducted the largest genomic analysis of M. tuberculosis to date, examining 7890 high-quality genomes from 82 countries (1900-2024) retrieved from NCBI GenBank. Rigorous quality filtering using CheckM ensured retention of genomes with >90% completeness and 99.6% of isolates carried only three core genes (erm(37), blaC, and aac(2')-Ic), whereas all other resistance genes occurred in