INOSITOL PHOSPHATE CAPPING OF THE NONREDUCING TERMINI OF LIPOARABINOMANNAN FROM RAPIDLY GROWING STRAINS OF MYCOBACTERIUM

Previous studies have demonstrated that the nonreducing termini of the lipoarabinomannan (LAM) from Mycobacterium tuberculosis are extensive ly capped with mannose residues, whereas those from a fast growing Myc obacterium sp., once thought to be an attenuated strain of M. tubercul osis, are not. The noncapped LAM, termed AraLAM, is known to be more p otent than the mannose capped LAM (ManLAM) in inducing functions assoc iated with macrophage activation. Using a combination of chemical and enzymatic approaches coupled with fast atom bombardment-mass spectrome try analysis, we demonstrated that LAMs from all M. tuberculosis strai ns examined (Erdman, H37Ra, and H37Rv), as well as the attenuated Myco bacterium bovis BCG strain, are mannose-capped with the extent of capp ing varying between 40 and 70%. The nonreducing termini of LAM from My cobacterium leprae were also found to be capped with mannoses but at a significantly lower level. A novel inositol phosphate capping motif w as identified on a minor portion of the otherwise uncapped arabinan te rmini of LAMs from the fast growing Mycobacterium sp. and Mycobacteriu m smegmatis ATCC 14468 and mc(2)155. In addition, an inositol phosphat e tetra-arabinoside was isolated from among endoarabinase digestion pr oducts of AraLAM and was shown to induce tumor necrosis factor-a produ ction. Accordingly, we concluded that AraLAM is characteristic of some rapidly growing Mycobacterium spp. It is distinct from ManLAMs of M. tuberculosis, M. bovis BCG, and Mycobacterium leprae not only in the a bsence of mannose-capping but also in containing some terminal inosito l phosphate substituents which may account for its particular potency in inducing macrophage activation.