The overall objective of this contract is to facilitate discovery and development of therapies with potential for treatment and prophylaxis of Pneumocystis carinii pneumonia in people with AIDS. The expected performance of this contract is to quantitatively evaluate therapeutic agents for efficacy against Pneumocystis carinii pneumonia in a standardized, validated mouse model test system, to include evaluation of therapies in combination in the primary mouse model, drug evaluations in prophylaxis protocols in the primary mouse model, and evaluation of treatment therapies in a rat model. Therapeutic agents will be evaluated for activity in a standardized, reproducible and validated in vitro (culture) test system which employs intact organisms.

Project Start
1997-09-01
Project End
2002-08-31
Budget Start
1997-09-16
Budget End
1999-08-31
Support Year
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Cushion, Melanie T; Linke, Michael J; Ashbaugh, Alan et al. (2010) Echinocandin treatment of pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infection. PLoS One 5:e8524
Joffrion, Tiffany M; Collins, Margaret S; Sesterhenn, Thomas et al. (2010) Functional characterization and localization of Pneumocystis carinii lanosterol synthase. Eukaryot Cell 9:107-15
Vale, Nuno; Collins, Margaret S; Gut, Jiri et al. (2008) Anti-Pneumocystis carinii and antiplasmodial activities of primaquine-derived imidazolidin-4-ones. Bioorg Med Chem Lett 18:485-8
Sesterhenn, Thomas M; Cushion, Melanie T; Slaven, Bradley E et al. (2006) Sequence of the mitochondrial genome of Pneumocystis carinii: implications for biological function and identification of potential drug targets. J Eukaryot Microbiol 53 Suppl 1:S154-5
Joffrion, Tiffany M; Collins, Margaret S; Cushion, Melanie T (2006) Microaerophilic conditions increase viability and affect responses of Pneumocystis carinii to drugs in vitro. J Eukaryot Microbiol 53 Suppl 1:S117-8
Cushion, Melanie T; Walzer, Peter D; Collins, Margaret S et al. (2004) Highly active anti-Pneumocystis carinii compounds in a library of novel piperazine-linked bisbenzamidines and related compounds. Antimicrob Agents Chemother 48:4209-16
Vanden Eynde, Jean Jacques; Mayence, Annie; Huang, Tien L et al. (2004) Novel bisbenzamidines as potential drug candidates for the treatment of Pneumocystis carinii pneumonia. Bioorg Med Chem Lett 14:4545-8
Collins, M S; Cushion, M T (2001) Standardization of an in vitro drug screening assay by use of cryopreserved and characterized Pneumocystis carinii populations. J Eukaryot Microbiol Suppl:178S-179S
Cushion, M T; Collins, M; Hazra, B et al. (2000) Effects of atovaquone and diospyrin-based drugs on the cellular ATP of Pneumocystis carinii f. sp. carinii. Antimicrob Agents Chemother 44:713-9
Cushion, M T; Linke, M J; Collins, M et al. (1999) The minimum number of Pneumocystis carinii f. sp. carinii organisms required to establish infections is very low. J Eukaryot Microbiol 46:111S

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