Structural analysis of an unusual bioactive N-acylated lipo-oligosaccharide LOS-IV in Mycobacterium marinum |
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Authors: | Rombouts Yoann Elass Elisabeth Biot Christophe Maes Emmanuel Coddeville Bernadette Burguière Adeline Tokarski Caroline Buisine Eric Trivelli Xavier Kremer Laurent Guérardel Yann |
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Affiliation: | Universite? de Lille 1, Unite? de Glycobiologie Structurale et Fonctionnelle, UGSF, F-59650 Villeneuve d'Ascq, France. |
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Abstract: | Although lipo-oligosaccharides (LOSs) are recognized as major parietal components in many mycobacterial species, their involvement in the host-pathogen interactions have been scarcely documented. In particular, the biological implications arising from the high degree of structural species-specificity of these glycolipids remain largely unknown. Growing recognition of the Mycobacterium marinum-Danio rerio as a specific host-pathogen model devoted to the study of the physiopathology of mycobacterial infections prompted us to elucidate the structure-to-function relationships of the elusive end-product, LOS-IV, of the LOS biosynthetic pathway in M. marinum. Combination of physicochemical and molecular modeling methods established that LOS-IV resulted from the differential transfer on the caryophyllose-containing LOS-III of a family of very unusual N-acylated monosaccharides, naturally present as different diastereoisomers. In agreement with the partial loss of pathogenecity previously reported in a LOS-IV-deficient M. marinum mutant, we demonstrated that this terminal monosaccharide conferred to LOS-IV important biological functions, including macrophage activating properties. |
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