Structure and antigenicity of lipoarabinomannan from Mycobacterium bovis BCG

Abstract

Lipoarabinomannan (LAM), a major lipoglycan of the mycobacterial cell envelope, was previously recognized as existing in two major forms: LAM with arabinofuranosyl (Araf)-containing termini (AraLAM) and a mannose-capped version (ManLAM) in which the majority of these termini are modified by additional mannose residues. Since ManLAM was first recognized in the virulent (Erdman) strain of Mycobacterium tuberculosis and the noncapped version in a rapidly growing, attenuated, H37Ra strain, it was thought that mannose capping may be a key factor in virulence. In the present study, LAM from M. bovis BCG was isolated and the non-reducing termini sequenced through differential O-alkylation, partial depolymerization and gas chromatography-mass spectrometric analyses of fragments. LAM from M. bovis BCG contains a short mannan backbone, highly branched arabinofuranosyl-containing side chains and several mannosyl residues capping the non-reducing termini of these side chains. Thus, LAM from M. bovis BCG is of the ManLAM type, showing no major structural differences at the non-reducing ends from the M. tuberculosis Erdman product. This observation led us to examine the earlier strain and to conclude that it showed little resemblance to conventional strains of M. tuberculosis. Thus, the absence of mannose caps may be more a feature of rapid growth than of avirulence. These results demonstrate that the relationship between mannose capping and disease induction is not a simple one. However, use of a panel of LAM-specific monoclonal antibodies showed antigenic differences between the BCG and the Erdman products, suggesting the presence of features specific to the different strains and pointing to LAM as a molecule within which further species and strain variations reside.