Evolution of transmissibility

Mtb has infected human host for at least 6000 years but still remains the leading cause of human death due to a single infectious agent, with more than 10.6 million new cases and 1.6 million deaths each year. Mtb is an obligate human pathogen that is outstandingly successful in airborne transmission. Little is known regarding how Mtb diverged from its cousin species and adapted to this distinctive ecological niche. Mtb population is clonal because its common ancestor somehow lost the ability of horizontal gene transfer (HGT). And because of that, the entire Mtb population was once considered to be a single bacterial strain until it was recently appreciated that Mtb comprises 9 lineages that differ by hundreds to thousands of mutations.


The recognition of Mtb lineages is significant, as the ongoing transmission of TB is mainly driven by strains of lineages that recently evolved and are highly transmissible. For example, our previous work demonstrated that more than 80% of TB cases in China were caused by a locally evolved sublineage. However, little is known about the underlying mechanisms of how certain strains evolved to be so successful. In this lab, we leverage population genomics approaches to identify bacterial variants that are underlying the evolution of transmissibility and further utilize cutting-edge experimental microbiology tools to dissect the underlying mechanisms. Understanding the mechanisms of Mtb transmission will facilitate the development of new vaccines and new anti-tuberculosis drugs to target the ones that are actually causing the epidemic, and thus contribute to the ultimate eradication of TB.