MYCOBACTERIAL CELL WALL AND DRUG DISCOVERY

Colorado State University, Fort Collins CO

Investigators

Linked publications & trials

Abstract

The centerpiece of this proposal is the new found, extraordinary[unreadable] lipooligosaccharide antigens, ubiquitous among atypical (nontuberculous)[unreadable] mycobacteria and perhaps present in Mycobacterium tuberculosis and[unreadable] Mycobacterium leprae. Those from Mycobacterium kansasii are characterized[unreadable] by a glycosidic trehalose-containing "core", modulated by species-specific[unreadable] sugars and acyl substituents. State-of-the-art chemical analysis (e.g. 360[unreadable] MHz 1H- and 13C-NMR; gas liquid chromatography/mass spectrometry; fast atom[unreadable] bombardment/mass spectrometry) will be applied, probing the variety of[unreadable] trehalose-containing "cores" and the relationship of species-specific[unreadable] sugars and acyl functions to the "cores". Analysis of the pyruvic[unreadable] acid-containing "C-mycoside" glycopeptidolipid (GPL) antigens of the[unreadable] Mycobacterium avium/Mycobacterium intracellulare/Mycobacterium scrofulaceum[unreadable] complex will continue in concert with a probing of their biosynthesis,[unreadable] based on observations that they originate in water-soluble glycopeptides[unreadable] and are susceptible to D cycloserine. The role of lysogenic conversion in[unreadable] the multiplicity of glycopeptidolipid-containing serotypes in nature will[unreadable] be explored. In addition, the clinical application of the species-specific[unreadable] glycolipids, incorporated into enzyme linked immunosorbent assays, in[unreadable] identification of pathogens and direct serodiagnosis of disease will[unreadable] continue. The physiological function and role in pathogenesis/persistence[unreadable] of the species-specific lipooligosaccharides/glycopeptidolipids will be[unreadable] explored with emphasis on the theorm of an inert lipoidal capsule.[unreadable] [unreadable]