02504nas a2200313 4500000000100000008004100001260001600042653002400058653003000082653002600112653001800138653001800156653003100174653002500205653002400230653002400254653002500278653002800303653003100331653002600362653002000388100001500408700001600423245013400439300001100573490000800584520158400592022001402176 1990 d c1990 Jun 0510aAntigens, Bacterial10aCarbohydrate Conformation10aCarbohydrate Sequence10aCell Membrane10aGlycosylation10aHydrogen-Ion Concentration10aImmunohistochemistry10aInositol Phosphates10aLipopolysaccharides10aMicroscopy, Electron10aMolecular Sequence Data10aMycobacterium tuberculosis10aPhosphatidylinositols10aPhosphorylation1 aHunter S W1 aBrennan P J00aEvidence for the presence of a phosphatidylinositol anchor on the lipoarabinomannan and lipomannan of Mycobacterium tuberculosis. a9272-90 v2653 a
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.
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