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The  Mycobacterium tuberculosis  cell envelope has been evolving over time to make the bacterium transmissible and adaptable to the human host. In this context, the  M. tuberculosis  cell envelope contains a peripheral barrier full of lipids, some of them unique, which confer  M. tuberculosis  with a unique shield against the different host environments that the bacterium will encounter at the different stages of infection. This lipid barrier is mainly composed of glycolipids that can be characterized by three different subsets: trehalose-containing, mannose-containing, and 6-deoxy-pyranose-containing glycolipids. In this review, we explore the roles of these cell envelope glycolipids in  M. tuberculosis  virulence and pathogenesis, drug resistance, and further, how these glycolipids may dictate the  M. tuberculosis  cell envelope evolution from ancient to modern strains. Finally, we address how these  M. tuberculosis  cell envelope glycolipids are impacted by the host lung alveolar environment, their role in vaccination and masking host immunity, and subsequently the impact of these glycolipids in shaping how  M. tuberculosis  interacts with host cells, manipulating their immune response to favor the establishment of an infection.

Underestimated Manipulative Roles of Mycobacterium tuberculosis Cell Envelope Glycolipids During Infection