Discovery of new immunomodulatory lipids of Mycobacterium tuberculosis – TB-ModuLip

As potent immunomodulatory molecules, Mycobacterium tuberculosis (Mtb) (glyco)lipids are key players in host-pathogen interactions. This repertoire has been essentially characterized by studying the composition of the envelope of the bacillus grown in broth culture and with the use of conventional biochemistry methods. Evidences strongly support that our knowledge of this repertoire and its immunomodulatoryproperties is incomplete: i) several lipid biosynthesis genes remain uncharacterised, ii) Mtb lipidome is very likely remodelled during infection, iii) yet poorly characterised, Mtb lipids are released from the bacillus and shuttled within host extracellular infections, which might have strong impact on the regulation of the host immune responses.
By taking advantage of the high sensitivity of last generation lipidomic approach, I performed global and unbiased analysis of the mycobacterial (glyco)lipid repertoire produced by different strains and present within the extracellular vesicles released by infected cells. I highlighted several uncharacterized lipids that are likely key mycobacterial immunomodulatory lipids because they are produced by virulent strains or during infection. The TB-ModuLip project aims characterizing the structure, the immunomodulatory properties and contribution to virulence of such lipids. It success would automatically lead to new concepts for the development of anti-TB tools.