Lineage-specific differences in lipid metabolism and its impact on clinical strains of Mycobacterium tuberculosis

Mycobacterium tuberculosis (M. tb) is the causative agent of TB and its incidences has been on the rise since 1993. Lipid metabolism is an imperative metabolic process, which grants M. tb the ability to utilize host-derived lipids as a secondary source of nutrition during infection. In addition to degrading host lipids, M. tb is proficient at using lipids, such as cholesterol, to facilitate its entry into macrophages. Mycolic acids, constituents of the mycobacterial cell wall, offer protection and aid in persistence of the bacterium. These are effectively synthesized using a complex fatty acid synthase system. Many pathogenesis studies have reported differences in lipid-metabolism of clinical strains of M. tb that belongs to diverse lineages of the Mycobacterium tuberculosis complex (MTBC). East-Asian and Euro-American lineages possess "unique" cell wall-associated lipids compared to the less transmissible Ethiopian lineage, which may offer these lineages a competitive advantage. Therefore, it is crucial to comprehend the complexities among the MTBC lineages with lipid metabolism and their impact on virulence, transmissibility and pathogenesis. Thus, this review provides an insight into lipid metabolism in various lineages of the MTBC and their impact on virulence and persistence during infection, as this may provide critical insight into developing novel therapeutics to combat TB.