Human adaptation and transmissibility of Mycobacterium tuberculosis genetic lineages. A genomic epidemiology study to guide TB control

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The main causative agent of tuberculosis (TB), Mycobacterium tuberculosis (Mtb), is responsible for more deaths annually than any other single infectious agent. Mtb bacteria are separated into eight genetic lineages and preliminary data supports differences in virulence and transmissibility among them. Globally, Mtb lineages show distinct geographical patterns that parallel that of human subpopulations suggesting co-adaption between host and pathogen. It is unknown if this geographic pattern will continue to be observed in cosmopolitan societies where different human subpopulations live in close proximity, and Mtb lineages have the opportunity to infect ‘naive’ hosts without co-adaptation. Assessing if and why Mtb lineages have variable transmissibility and if they are indeed adapted to different human subpopulations can help guide disease control and improve our understanding of biological host pathogen relationships. Using epidemiological and whole genome sequencing data from an international consortium, this project aims to investigate the relationship between Mtb lineage and disease transmissibility across and within human subpopulations. A genome wide association approach will be employed to fine map specific Mtb genetic loci associated with the transmissibility phenotype. Investigating adaptation between Mtb and its human host will define combinations of Mtb lineage and host ancestry most prone to progression and transmission. This can ultimately help refine disease containment strategies such as latent TB chemoprophylaxis and targeted contact tracing to achieve WHO End TB goals of eliminating TB by 2035.