The Global Population Structure of the MTBC

MTBC Lineages

The MTBC is composed of obligate pathogens adapted to different mammalian hosts. In addition to the ten human-adapted lineages, the MTBC also includes several lineages adapted to different wild and domestic animal species. 

We previously discovered a novel MTBC variant in a wild chimpanzee from Cote d’Ivoire as well as an extinct MTBC variant in pre-Columbian human skeletons from Peru.

Recently we’ve proposed a nomenclature for livestock associated MTBC members to aid in understanding the epidemiology of these strains that threaten agricultural resources.

Generalists and Specialists in the MTBC

In the past we showed that the human-adapted MTBC lineages can be further divided into sub-lineages, which differ in their epidemiological characteristics. For example, among the 10 sub-lineages identified in Lineage(L) 4, some behave as specialists and are limited to specific geographical areas, while others are generalists occurring on all continents. On a broader scale, some lineages such as L2 and L4 are globally distributed, whereas others like L5-L10 are exclusive to Africa.

Conserved Human T Cell Epitopes

Our previous work showed that, in contrast to most other human pathogens which evade host immune responses by accumulating antigenic variation, human T cell antigens in the MTBC are highly conserved. This suggests that some of the host immune responses in TB benefit the bacteria, e.g. by promoting lung damage in the patient, leading to increased transmission. These findings have important implications for the development of new TB diagnostics and vaccines. 

Ongoing Research

Our ongoing work explores structural variation in the MTBC using long read DNA sequencing technology. We are also exploring the co-evolution between the MTBC and different human and livestock populations to see how MTBC diversity interacts with host genetic variation, and how this interaction reflects in experimental, clinical and epidemiological phenotypes.