Deciphering the Genetic Bases of the Structural Diversity of Phenolic Glycolipids in Strains of theMycobacterium tuberculosisComplex

摘要: Phenolic glycolipids (PGL) play a major role in the virulence of mycobacteria, notably strains Mycobacterium tuberculosis complex and leprae. The structure carbohydrate domain these compounds is highly variable, genetic bases for variations remain unknown. We demonstrated that monoglycosylated PGL formed by bovis differs from triglycosylated synthesized M. (PGL-tb) because following two defects: frameshift mutation within gene Rv2958c, encoding glycosyltransferase involved transfer second rhamnosyl residue PGL-tb, deletion region encompasses genes, which encode GDP-d-mannose 4,6-dehydratase GDP-4-keto-6-deoxy-d-mannose-3,5-epimerase/reductase, required formation activated l-fucose. Expression three genes BCG allowed synthesis PGL-tb this recombinant strain. Additionally, we showed all bovis, microti, pinnipedii, some africanum harbor same their Rv2958c orthologs. Consistently, PGLs purified (harboring mutation) pinnipedii revealed are PGL. These findings explain specificity production have important implications our understanding evolution complex.