Abstract

This application represents a biological approach to the development of new forms of treatment of opportunistic infections in the acquired immune deficiency syndrome (AIDS). The approach involves five projects which focus on metabolic and biochemical studies of opportunistic fungi and protozoa which will provide important information about their nutrient requirements and lead to the development of new therapeutic targets. Project 1 deals with the development of an axenic culture system for Pneumocystis carinii. Project 2 focuses on the analysis of the transport and metabolism of the lipids of P. carinii. Project 3 involves studies of purine metabolism of Toxoplasma gondii and P. carinii. Project 4 is concerned with D-mannitol metabolism in Cryptococcus neoformans. Project 5 deals with studies of the cytochrome P450 lanosterol 14-alpha-demethylase and NADPH-cytochrome P450 reductase genes of C. neoformans. The application emphasizes close collaboration and communication among investigators so that knowledge gained about one organism can be applied to other opportunistic pathogens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI031702-02
Application #
3547869
Study Section
Special Emphasis Panel (SRC (60))
Project Start
1991-09-01
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221

  Publications

Dohn, M N; White, M L; Vigdorth, E M et al. (2000) Geographic clustering of Pneumocystis carinii pneumonia in patients with HIV infection. Am J Respir Crit Care Med 162:1617-21
Javaid, Z Z; el Kouni, M H; Iltzsch, M H (1999) Pyrimidine nucleobase ligands of orotate phosphoribosyltransferase from Toxoplasma gondii. Biochem Pharmacol 58:1457-65
De Stefano, J A; Myers, J D; Du Pont, D et al. (1998) Cell wall antigens of Pneumocystis carinii trophozoites and cysts: purification and carbohydrate analysis of these glycoproteins. J Eukaryot Microbiol 45:334-43
Flynn, T M; Niehaus, W G (1997) Improved method for isolation of DNA from slow-growing basidiomycetes such as Armillaria mellea. Biotechniques 22:47, 50-2
Beach, D H; Chen, F; Cushion, M T et al. (1997) Effects of steroidal allenic phosphonic acid derivatives on the parasitic protists Leishmania donovani, Leishmania mexicana mexicana, and Pneumocystis carinii carinii. Antimicrob Agents Chemother 41:162-8
Theus, S A; Andrews, R P; Linke, M J et al. (1997) Characterization of rat CD4 T cell clones specific for the major surface glycoprotein of Pneumocystis carinii. J Eukaryot Microbiol 44:96-100
Chaturvedi, V; Flynn, T; Niehaus, W G et al. (1996) Stress tolerance and pathogenic potential of a mannitol mutant of Cryptococcus neoformans. Microbiology 142 ( Pt 4):937-43
Niehaus, W G; Richardson, S B; Wolz, R L (1996) Slow-binding inhibition of 6-phosphogluconate dehydrogenase by zinc ion. Arch Biochem Biophys 333:333-7
Chaturvedi, V; Wong, B; Newman, S L (1996) Oxidative killing of Cryptococcus neoformans by human neutrophils. Evidence that fungal mannitol protects by scavenging reactive oxygen intermediates. J Immunol 156:3836-40
Ellis, J E; Wyder, M A; Zhou, L et al. (1996) Composition of Pneumocystis carinii neutral lipids and identification of coenzyme Q10 as the major ubiquinone homolog. J Eukaryot Microbiol 43:165-70

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