ANALYSIS AND SYNTHESIS OF CARBOHYDRATE ANTIGENS OF MYCOBACTERIUM TUBERCULOSIS

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Mycobacterium tuberculosis, the causative organism of tuberculosis is responsible for approximately three million death cases annually and the mortality rate of infections caused by multiple drug-resistant strains of this bacterium exceeds 80%. M. tuberculosis is coated by a number of polysaccharides of unusual structure. A unique component termed polysaccharide II is said to be composed of alpha 1,2-linked D-glucose residues. Schemes were designed to isolate this polysaccharide from polysaccharide-containing extracts of M. tuberculosis. In search for this putative antigen we chemically synthesized oligosaccharides correponding to polysaccharide II and developed methods for their covalent attachment to proteins to render them immunogenic, in a controlled manner. We demonstrated that the major monosaccharide components in soluble polysaccharide fractions from Mycobacteria are glucose, arabinose, mannose and galactose. A number of polysaccharide fractions were analyzed and some were found to contain mainly or exclusively d-glucose. Nuclear magnetic resonance spectra indicate that the glucose-containing polysaccharide fractions have the same overall structure as the glycogen-like polysaccharide isolated from M. tuberculosis many years ago by Siebert. None of the polysaccharide fractions appeared to be identical to the putative polysaccharide II.