title: Consequences of genomic diversity in Mycobacterium tuberculosis.
abstract: The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically widespread Lineage 2 (includes Beijing) and Lineage 4 (also known as Euro-American) are more virulent than other lineages that are more geographically restricted. This increased virulence is associated with delayed or reduced pro-inflammatory host immune responses, greater severity of disease, and enhanced transmission. Future work should focus on the interaction between MTBC and human genetic diversity, as well as on the environmental factors that modulate these interactions.
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland.
authors.forename: Mireia
authors.initials: M
authors.lastname: Coscolla
authors.affiliation: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, Basel 4003, Switzerland. Electronic address: Sebastien.Gagneux@unibas.ch.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
mesh_terms: D014644:Genetic Variation; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D010641:Phenotype; D010802:Phylogeny; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000473:pathology* / Q000635:transmission; D014774:Virulence
keywords: Diversity; Genome; Lineage; SNP; Transmission; Virulence