Diversity and disease pathogenesis in Mycobacterium tuberculosis

The increasing availability of whole-genome sequence (WGS) data for Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), suggests that circulating genotypes have been molded by three dominant evolutionary forces: long-term persistence within the human population, which requires a core programme of infection, disease, and transmission; selective pressure on specific genomic loci, which provides evidence of lineage-specific adaptation to host populations; and drug exposure, which has driven the rapid emergence of resistant isolates following the global implementation of anti-TB chemotherapy. Here, we provide an overview of these factors in considering the implications of genotypic diversity for disease pathogenesis, vaccine efficacy, and drug treatment.