title: Diversity and disease pathogenesis in Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa. Electronic address: Digby.warner@uct.ac.za.
authors.forename: Digby F
authors.initials: DF
authors.lastname: Warner
authors.affiliation: MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Koch
authors.affiliation: MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, Institute of Infectious Disease and Molecular Medicine and Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa. Electronic address: valerie.mizrahi@uct.ac.za.
authors.forename: Valerie
authors.initials: V
authors.lastname: Mizrahi
mesh_terms: D056726:Genetic Association Studies; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity*; D049490:Systems Biology; D014376:Tuberculosis / Q000175:diagnosis / Q000382:microbiology
keywords: Mycobacterium tuberculosis; drugs; epistasis; evolution; genomics; mutagenesis; vaccine