The recent availability (Hunter, S.W., Gaylord, H., and Brennan, P.J. (1986) J. Biol. Chem. 261, 12345-12351) of the well known
arabinomannan of Mycobacterium leprae and Mycobacterium tuberculosis as the pure native
lipoarabinomannan has resulted in its implication in key aspects of the immunopathogenesis of
leprosy and
tuberculosis. We had indicated that the
lipid moiety of
lipoarabinomannan is probably based on a
diacylglycerol unit in that
glycerol and the two
fatty acids, hexadecanoate and 10-methyloctadecanoate, were identified. In addition,
lipoarabinomannan was also shown to contain myo-
inositol 1-phosphate. Evidence is now presented, based on selective radiolabeling and analysis of various cleavage fragments, that the
inositol phosphate exists as both an alkalilable phosphodiester and as part of a
phosphatidylinositol "membrane anchor." The
mannan of M.
tuberculosis was also isolated as the native
lipomannan. It also apparently contains a
phosphatidylinositol unit but is devoid of the
alkali-labile
inositol phosphate residues. These
lipopolysaccharides are apparently multiglycosylated versions of the well known myocobacterial mannosyl
phosphatidylinositols and are prokaryotic versions of the growing list of
phosphatidylinositol-anchored macromolecules. Immunogold labeling demonstrates that
lipoarabinomannan is a true antigenic capsular or extracellular product of M.
tuberculosis. The presence of a
phosphatidylinositol residue on
lipoarabinomannan may explain its interaction with macrophage membranes and role in mycobacterial pathogenesis.