“…In this regard, the role of the cell envelope lipids in the transition of environmental mycobacteria becoming highly transmissible, pathogenic and host-dependent is pointed out (102). The possibility that ancient M. tuberculosis complex strains such as M. canettii, mainly isolated in the horn of Africa (172,173), have evolved has been explored, that is, changing their metabolism and increasing their cell envelope hydrophobicity as they evolved to the modern M. tuberculosis complex strains, e.g., changing their cell envelope's outmost exposed lipid polarity and thus evolving into a more hydrophobic organism. This was achieved by stopping the production of polar lipids such as LOSs or PGLs (which currently are just described in a subset of M. tuberculosis complex modern strains, Beijing clinical isolates), reducing their polarity (e.g., by losing sugars or adding acyl chains in their cell envelope glycolipids, e.g., DAT, TAT, PAT, SLs, TDM, TMM), and increasing the presence of apolar lipids in their cell envelopes [e.g., dimycocerosates of the phthiocerol family (PDIMs)] (102).…”