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 non-capped 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.
BarnesP. F.,
FongS.-J.,
BrennanP. J.,
TwomeyP. E.,
MazumderA.,
ModlinR. L.1990; Local production of tumor necrosis factor and INF-γ in tuberculous pleuritis. Journal of Immunology 145:149–154
ChanJ.,
FanX.,
HunterS. W.,
BrennanP. J.,
BloomB. R.1991; Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages. Infection and Immunity 59:1755–1761
ChatterjeeD.,
BozicC. M.,
McneilM.,
BrennanP. J.1991; Structural features of the arabinan component of the lipoarabinomannan of Mycobacterium tuberculosis. Journal of Biological Chemistry 266:9652–9660
ChatterjeeD.,
HunterS. W.,
McneilM.,
BrennanP. J.1992a; Lipoarabinomannan. Multiglycosylated form of the mycobacterial mannosylphosphatidylinositols. Journal of Biological Chemistry 267:6228–6233
ChatterjeeD.,
LowellK.,
RivoireB.,
McneilM.,
BrennanP. J.1992b; Lipoarabinomannan of Mycobacterium tuberculosis,Capping with mannosyl residues in some strains. Journal of Biological Chemistry 267:6234–6239
ChatterjeeD.,
RobertsA. D.,
LowellK.,
BrennanP. J.,
OrmeI.1992c; Structural basis of lipoarabinomannan to induce secretion of tumor necrosis factor. Infection and Immunity 60:1249–1253
ChujorC. S. N.,
KuhnB.,
SchwererB.,
BernheimerH.,
LevisW. R.,
BevecD.1992; Specific inhibition of mRNA accumulation for lymphokines in human T cell line Jurkat by mycobacterial lipoarabinomannan antigen. Clinical and Experimental Immunology 87:398–403
DafféM.,
BrennanP. J.,
McneillM.1990; Predominant structural features of the cell wall arabinogalactan of Mycobacterium tuberculosis as revealed through characterization of oligoglycosyl alditol fragments by gas chromatography/mass spectrometry and by 1H and 13C NMR analyses. Journal of Biological Chemistry 265:6734–6743
DuboisM.,
GillesK. A.,
HamiltonJ. K.,
RebersP. A.,
SmithF.1966; Colorimetric method for determination of sugars and related substances. Analytical Chemistry 28:350–356
GerwigG. J.,
KamerlingJ. P.,
VliegenthartJ. F. G.1978; Determination of the d and l natural configuration of monosaccharides by high-resolution capillary g.l.c. Carbohydrate Research 62:349–357
HunterS. W.,
BrennanP. J.1990; Evidence for the presence of a phosphatidylinositol anchor on the lipoarabinomannan and lipomannan of Mycobacterium tuberculosis. Journal of Biological Chemistry 265:9272–9279
HunterS. W.,
GaylordH.,
BrennanP. J.1986; Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli. Journal of Biological Chemistry 261:12345–12351
KaplanG.,
GandhiR. R.,
WeinsteinD. E.,
LevisW. R.,
PatarroyoM. E.,
BrennanP. J.,
CohnZ. A.1987; Mycobacterium leprae antigen-induced suppression of T cell proliferation in vitro. Journal of Immunology 138:3028–3034
LevisW. R.,
MeekerH. C.,
Schuller-LevisG.,
SersenE.,
BrennanP. J.,
FriedP.1987; Mycobacterial carbohydrate antigens for serological testing of patients with leprosy. Journal of Infectious Diseases 156:763–769
LipkindG. M.,
ShashkovA. S.,
KnirelY. A.,
VinogradovE. V.,
KochetkovN. K.1988; A computer-assisted structural analysis of regular polysaccharides on the basis of 13C-N.M.R. data. Carbohydrate Research 175:59–75
MinnikinD. E.,
AlshamaonyL.,
GoodfellowM.1975; Differentiation of Mycobacterium, Nocardia and related taxa by thin layer chromatographic analysis of whole cell methanolysates. Journal of General Microbiology 88:200–204
MisakiA.,
AzumaI.,
YamamuraY.1977; Structural and immunochemical studies on d-arabino-d-mannans and d-mannans of Mycobacterium tuberculosis and other Mycobacterium species. Journal of Biochemistry 82:1759–1770
MolloyA.,
GaudernackG.,
LevisW. R.,
CohnZ. A.,
KaplanG.1990; Suppression of T-cell proliferation by Mycobacterium leprae and its products: the role of lipopolysaccharide. Proceedings of the National Academy of Sciences of the United States of America 87:973–977
MorenoC.,
MehlertA.,
LambJ.1988; The inhibitory effects of mycobacterial lipoarabinomannan and polysaccharides upon polyclonal and monoclonal human T cell proliferation. Clinical and Experimental Immunology 74:206–210
MorenoC.,
TaverneJ.,
MehlertA.,
BateC. A. W.,
BrealeyR. J.,
MeagerA.,
RookG. A. W.,
PlayfairJ. H. L.1989; Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumor necrosis factor from human and murine macrophages. Clinical and Experimental Immunology 76:240–245
SibleyL. D.,
HunterS. W.,
BrennanP. J.,
KrahenbuhlJ. L.1988; Mycobacterial lipoarabinomannan inhibits gamma interferon-mediated activation of macrophages. Infection and Immunity 56:1232–1236
SibleyL. D.,
AdamsL. B.,
KrahenbuhlJ. L.1990; Inhibition of interferon-gamma-mediated activation in mouse macrophages treated with lipoarabinomannan. Clinical and Experimental Immunology 80:141–148
SugdenE. A.,
SamaghB. S.,
BundleD. R.,
DuncanJ. R.1987; Lipoarabinomannan and lipid-free arabinomannan antigens of Mycobacterium paratuberculosis. Infection and Immunity 55:762–770