Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI018357-06
Application #
3444559
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1981-01-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Colorado State University-Fort Collins
Department
Type
Schools of Veterinary Medicine
DUNS #
112617480
City
Fort Collins
State
CO
Country
United States
Zip Code
80523

  Publications

Larrouy-Maumus, Gérald; Gilleron, Martine; Skovierová, Henrieta et al. (2015) A glycomic approach reveals a new mycobacterial polysaccharide. Glycobiology 25:1163-71
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
Bhamidi, Suresh; Scherman, Michael S; Jones, Victoria et al. (2011) Detailed structural and quantitative analysis reveals the spatial organization of the cell walls of in vivo grown Mycobacterium leprae and in vitro grown Mycobacterium tuberculosis. J Biol Chem 286:23168-77
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
Amin, Anita G; Angala, Shiva K; Chatterjee, Delphi et al. (2009) Rapid screening of inhibitors of Mycobacterium tuberculosis growth using tetrazolium salts. Methods Mol Biol 465:187-201
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
Kaur, Devinder; Guerin, Marcelo E; Skovierová, Henrieta et al. (2009) Chapter 2: Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis. Adv Appl Microbiol 69:23-78
Mahapatra, Sebabrata; Crick, Dean C; McNeil, Michael R et al. (2008) Unique structural features of the peptidoglycan of Mycobacterium leprae. J Bacteriol 190:655-61

Showing the most recent 10 out of 134 publications