Understanding the evolution of Mycobacterium tuberculosis lineages using an integrated genomics and metabolomics approach

Abstract

Despite being the number one cause of death from an infectious disease, little is known of the 7 phylogenetic lineages of Mycobacterium tuberculosis (Mtb). These lineages are thought to have adapted differently to their human hosts, as they are geographically localised. As a result, they show variation at the phenotype level, such as virulence and the ability to develop antibiotic resistance, and at a genomic level, such as in single nucleotide polymorphisms (SNPs). We have linked the differences in SNPs between lineages to differences in metabolites (i.e. what is ultimately produced by a cell). Through multi-omic integration of these datasets we have discovered lineage-specific metabolomic changes, potentially as a result of genomic adaptation. The differences between lineages will provide insight into new biological pathways to target and manipulate in future research.