Highly ordered supra-molecular organization of the mycobacterial lipoarabinomannans in solution. Evidence of a relationship between supra-molecular organization and biological activity.
The complex mycobacterial mannosylated lipoarabinomannans (ManLAMs) are currently considered to be the major virulence factors of the pathogenic Mycobacterium tuberculosis. The recognition and the interaction of ManLAMs with immune system receptors have been shown to promote M.tuberculosis phagocytosis but also to down-regulate the bactericidal immune response of the host in favor of the survival of the pathogenic bacilli. To date these original biological activities were mainly associated to the presence of mannose residues capping the non-reducing ends of the ramified polysaccharide moiety of these complex lipoglycans. However, we demonstrated recently that the molecular recognition of ManLAM terminal mannose units by human pulmonary surfactant protein A (hSP-A) carbohydrate recognition domains depends on the presence of the lipid moiety of the ManLAMs as proposed by Sidobre et al. in 2002. Thus, we investigated the putative role of the ManLAM aglycon moiety. The data presented here, indicate that the hydrophobic aglycon part of ManLAM is associated to a characteristic concentration-dependent supra-molecular organization of these complex molecules. Furthermore, we observed that the deacylated ManLAMs or the lipid-free mannosylated arabinomannans, which do not exhibit characteristic ManLAM activities, do not display this supra-molecular organization. These observations strongly suggest that the ManLAMs immunomodulatory activities might be associated to their particular organization. Finally, the determination of the critical micellar concentration of ManLAMs obviously supports the notion that this supra-molecular organization may be responsible for the specific biological activities of these complex molecules.
Rivière
Michel
M
Institut de Pharmacologie et de Biologie Structurale du CNRS, 205 route de Narbonne, 31077, Toulouse Cedex 4, France. michel.riviere@ipbs.fr
Moisand
André
A
Lopez
André
A
Puzo
Germain
G
D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D046911:Macromolecular Substances; D008823:Micelles; D008958:Models, Molecular; D015394:Molecular Structure; D009161:Mycobacterium / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020349:Surface Plasmon Resonance
D000942:Antigens, Bacterial; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D008823:Micelles; C050016:lipoarabinomannan