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Structural and functional features of Rhodococcus ruber lipoarabinomannan

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

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Abstract

The genus Rhodococcus is part of the phylogenetic group nocardioform actinomycetes, which also includes the genus Mycobacterium. Members of this phylogenetic group have a characteristic cell envelope structure, which is dominated by various complex lipids. Among these, lipoglycans are of particular interest since mycobacterial lipoarabinomannans are important immunomodulatory molecules that are likely to be involved in the subsequent fate of mycobacterial bacilli once inside phagocytic cells. Rhodococcus ruber is a species closely related to an established opportunistic human pathogen, Rhodococcus equi. This paper reports the isolation and characterization of R. ruber lipoarabinomannan, designated as RruLAM. SDS-PAGE and gas chromatography analyses revealed that RruLAM was of an intermediate size between Mycobacterium tuberculosis lipoarabinomannan and lipomannan. Using a combination of chemical degradation and 1H, 13C-NMR experiments, the carbohydrate structure of RruLAM was unambiguously shown to be composed of a linear (α1→6)-Manp backbone substituted at some O-2 positions by a single t-α-Araf sugar unit. Integration of the anomeric proton signals provided an indication of the degree of branching as approximately 45%. The RruLAM structure is much simpler than that established for M. tuberculosis lipoarabinomannan but is also different from that determined for the closely related species and opportunistic human pathogen, R. equi. RruLAM was unable to induce the production of TNF-α by either human or murine macrophage cell lines, suggesting that more sophisticated structures, such as phosphoinositol capping motifs, are required for such activity.


Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Microbiology

Year: 2003

Volume: 149

Issue: 6

Pages: 1437-1445

ISSN (print): 1350-0872

ISSN (electronic): 1465-2080

Publisher: Society for General Microbiology

URL: http://dx.doi.org/10.1099/mic.0.26161-0

DOI: 10.1099/mic.0.26161-0

PubMed id: 12777484


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