Structural analysis of an unusual bioactive N-acylated lipo-oligosaccharide LOS-IV in Mycobacterium marinum.
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.
Université de Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, UGSF, F-59650 Villeneuve d'Ascq, France.
Yoann
Y
Rombouts
Elisabeth
E
Elass
Christophe
C
Biot
Emmanuel
E
Maes
Bernadette
B
Coddeville
Adeline
A
Burguière
Caroline
C
Tokarski
Eric
E
Buisine
Xavier
X
Trivelli
Laurent
L
Kremer
Yann
Y
Guérardel
D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology*; D008262:Macrophage Activation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019910:Mycobacterium marinum / Q000276:immunology*; D019906:Nuclear Magnetic Resonance, Biomolecular
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides