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Identification of a novel mannose-capped lipoarabinomannan from Amycolatopsis sulphurea

Lookup NU author(s): Kevin Gibson, Dr Jerome Nigou, Professor Del Besra

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Abstract

The genus Amycolatopsis is a member of the phylogenetic group nocardioform actinomycetes, which also includes the genus Mycobacterium. Members of this group have a characteristic cell envelope structure, dominated by various complex lipids and polysaccharides. Amongst these, lipoglycans are of particular interest since mycobacterial lipoarabinomannans are important immunomodulatory molecules. In this study we report the isolation and structural characterization of Amycolatopsis sulphurea lipoarabinomannan, designated AsuLAM. SDS/PAGE analysis revealed that AsuLAM was of an intermediate size between Mycobacterium tuberculosis lipoarabinomannan and lipomannan, confirmed by matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry that predicted an average molecular mass of 10 kDa. Using a range of chemical degradations, NMR experiments and capillary electrophoresis analysis, AsuLAM was revealed as an original structure. The mannosyl-phosphatidyl-myo-inositol anchor exhibits a single acyl-form, characterized by a diacylated glycerol moiety, and contains, as one of the main fatty acids, 14-methylpentadecanoate, a characteristic fatty acid of the Amycolatopsis genus. AsuLAM also contains a short mannan domain; and is dominated by a multi-branched arabinan domain, composed of an (α1 → 3 5)-Araf (arabinofuranose) chain substituted, predominately at the O-2 position, by a single β-Araf. The arabinan domain is further elaborated by manno-oligosaccharide caps, with around one per molecule. This is the first description of manno-oligosaccharide caps found in a non-mycobacterial LAM. AsuLAM was unable to induce the production of the pro-inflammatory cytokine tumour necrosis factor a when tested with human or murine macrophage cell lines, reinforcing the paradigm that mannose-capped LAM are poor inducers of pro-inflammatory cytokines.


Publication metadata

Author(s): Gibson KJC, Gilleron M, Constant P, Puzo G, Nigou J, Besra GS

Publication type: Article

Publication status: Published

Journal: Biochemical Journal

Year: 2003

Volume: 372

Issue: 3

Pages: 821-829

ISSN (print): 0264-6021

ISSN (electronic): 1470-8728

Publisher: Portland Press

URL: http://dx.doi.org/10.1042/BJ20030197

DOI: 10.1042/BJ20030197

PubMed id: 12620092


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