title: Structural study of lipomannan and lipoarabinomannan from Mycobacterium chelonae. Presence of unusual components with alpha 1,3-mannopyranose side chains.
abstract: Lipomannan (LM) and lipoarabinomannan (LAM) are major glycolipids present in the mycobacterial cell wall that are able to modulate the host immune response. In this study, we have undertaken the structural determination of these important modulins in Mycobacterium chelonae, a fast growing pathogenic mycobacterial species. One-dimensional and two-dimensional NMR spectra were used to demonstrate that LM and LAM from M. chelonae, designated CheLM and CheLAM, respectively, possess structures that differ from the ones reported earlier in other mycobacterial species. Analysis by gas chromatography/mass spectrometry of the phosphatidyl-myo-inositol anchor, which is thought to play a role in the biological functions of these lipoglycans, pointed to a high degree of heterogeneity based on numerous combinations of acyl groups on the C-1 and C-2 positions of the glycerol moiety. Characterization of the mannan core of CheLM and CheLAM revealed the presence of novel alpha1,3-mannopyranosyl side chains. This motif, which reacted specifically with the lectin from Galanthus nivalis, was found to be unique among a panel of nine mycobacterial species. Then, CheLM and CheLAM were found to be devoid of both the mannooligosaccharide cap present in Mycobacterium tuberculosis and the inositol phosphate cap present in Mycobacterium smegmatis and other fast growing species. Tumor necrosis factor-alpha and interleukin-8 production were assessed from human macrophages with LAM preparations from different species. Our results suggest that the inositol phosphate capping may represent the major cytokine-inducing component of LAMs. This work not only underlines the diversity of LAM structures among various mycobacterial species but also provides new structures that could be useful to dissect the structure-function relationships of these complex molecules.
authors.affiliation: Laboratoire de Glycobiologie Structurale et Fonctionnelle, CNRS UMR8576, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Guerardel
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Maes
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Elass
authors.forename: Yves
authors.initials: Y
authors.lastname: Leroy
authors.forename: Philippe
authors.initials: P
authors.lastname: Timmerman
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Gérard
authors.initials: G
authors.lastname: Strecker
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
mesh_terms: D018949:Antigens, CD1 / Q000502:physiology; D002460:Cell Line; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D016926:Mycobacterium chelonae / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D016209:Interleukin-8; D037102:Lectins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C050016:lipoarabinomannan; C064351:lipomannan