Lipidomics and genomics of M. tuberculosis

Mycolic acids (MAs) are a-alkyl, ß-hydroxy long chain fatty acids found in abundance in the cell envelope of the Mycobacterium tuberculosis complex (MTBC). MAs form an efficient permeability barrier, modulate host innate immune responses, and are the targets of several anti-tuberculosis drugs. Using mass spectrometry, we measured the relative abundance of 80 MA species across 36 clinical isolates of MTBC covering four major phylogenetic lineages, and found significant variations in the MA patterns between different MTBC strains and lineages. Combining lipidomics and whole genome sequence data we showed that the MTBC strain genetic background influences mycolic acid metabolism and therefore emphasize the need to consider MTBC diversity in the emergence of drug resistance and the development of new antibiotics.