Core - Screening of New Antitubercular Compounds

Orme, Ian M.

Abstract

Core B presents an in vitro/murine bone marrow macrophage """"""""screen"""""""" to test compounds arising from projects 1 and 3 for evidence of specific activity in inhibiting the in vitro growth of a panel of clinical isolates and laboratory strains of M. tuberculosis. Because it is unlikely that significant numbers of new compounds will become available in the first year, work will begin in the second year. Moreover, formal; arrangements with the industrial partner (SmithKline Beecham; Project 3) have yet to be made. Subsequent testing of promising leads in our whole animals will come under Contract NIH, NIAID N01 AI-45239 (""""""""Animal Model Testing of Anti-TB Drugs""""""""; I.M. Orme, PI).

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Program--Cooperative Agreements (U19)
• Project #: 1U19AI038087-01
• Application #: 3727838
• Support Year: 1
• Fiscal Year: 1995

Institution

• Name: Colorado State University-Fort Collins
• DUNS #: 112617480
• City: Fort Collins
• State: CO
• Country: United States
• Zip Code: 80523

Publications

Phetsuksiri, Benjawan; Jackson, Mary; Scherman, Hataichanok et al. (2003) Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis. J Biol Chem 278:53123-30

Gibson, Kevin J C; Gilleron, Martine; Constant, Patricia et al. (2003) Structural and functional features of Rhodococcus ruber lipoarabinomannan. Microbiology 149:1437-45

Kremer, Laurent; Gurcha, Sudagar S; Bifani, Pablo et al. (2002) Characterization of a putative alpha-mannosyltransferase involved in phosphatidylinositol trimannoside biosynthesis in Mycobacterium tuberculosis. Biochem J 363:437-47

Nigou, Jerome; Besra, Gurdyal S (2002) Characterization and regulation of inositol monophosphatase activity in Mycobacterium smegmatis. Biochem J 361:385-90

Cooper, Howard N; Gurcha, Sudagar S; Nigou, Jerome et al. (2002) Characterization of mycobacterial protein glycosyltransferase activity using synthetic peptide acceptors in a cell-free assay. Glycobiology 12:427-34

Kremer, Laurent; Dover, Lynn G; Carrere, Severine et al. (2002) Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis. Biochem J 364:423-30

Gurcha, Sudagar S; Baulard, Alain R; Kremer, Laurent et al. (2002) Ppm1, a novel polyprenol monophosphomannose synthase from Mycobacterium tuberculosis. Biochem J 365:441-50

Nigou, Jerome; Besra, Gurdyal S (2002) Cytidine diphosphate-diacylglycerol synthesis in Mycobacterium smegmatis. Biochem J 367:157-62

Larsen, Michelle H; Vilcheze, Catherine; Kremer, Laurent et al. (2002) Overexpression of inhA, but not kasA, confers resistance to isoniazid and ethionamide in Mycobacterium smegmatis, M. bovis BCG and M. tuberculosis. Mol Microbiol 46:453-66

Hancock, Ian C; Carman, Stephen; Besra, Gurdyal S et al. (2002) Ligation of arabinogalactan to peptidoglycan in the cell wall of Mycobacterium smegmatis requires concomitant synthesis of the two wall polymers. Microbiology 148:3059-67