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

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI018357-27
Application #
7176916
Study Section
Special Emphasis Panel (NSS)
Program Officer
Jacobs, Gail G
Project Start
1981-01-01
Project End
2009-07-31
Budget Start
2007-02-01
Budget End
2009-07-31
Support Year
27
Fiscal Year
2007
Total Cost
$343,715
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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Ishizaki, Yoshimasa; Hayashi, Chigusa; Inoue, Kunio et al. (2013) Inhibition of the first step in synthesis of the mycobacterial cell wall core, catalyzed by the GlcNAc-1-phosphate transferase WecA, by the novel caprazamycin derivative CPZEN-45. J Biol Chem 288:30309-19
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Skovierová, Henrieta; Larrouy-Maumus, Gérald; Pham, Ha et al. (2010) Biosynthetic origin of the galactosamine substituent of Arabinogalactan in Mycobacterium tuberculosis. J Biol Chem 285:41348-55
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Scherman, Hataichanok; Kaur, Devinder; Pham, Ha et al. (2009) Identification of a polyprenylphosphomannosyl synthase involved in the synthesis of mycobacterial mannosides. J Bacteriol 191:6769-72
Skovierová, Henrieta; Larrouy-Maumus, Gérald; Zhang, Jian et al. (2009) AftD, a novel essential arabinofuranosyltransferase from mycobacteria. Glycobiology 19:1235-47
Eoh, Hyungjin; Brennan, Patrick J; Crick, Dean C (2009) The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target. Tuberculosis (Edinb) 89:1-11

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