Abstract

Current regimens for treating cryptococcal disease rely on drugs which, because of their narrow therapeutic index, can be extremely toxic. Lipid-based delivery systems provide an alternative mode of treatment which has proven to be promising for the administration of gentamicin (for mycobacterium infection), doxorubicin, and amphotericin B. In this last case, toxicity of amphotericin is dramatically attenuated, while the antifungal efficacy is maintained. Investigators at the Liposome Company, Inc. (TLC) will develop lipid- based formulations of antifungal peptides to be evaluated in Project 1 and 2. TLC scientists will also work with Project 3 investigators to develop carriers for growth-arresting pheromones.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AI031696-01
Application #
3804167
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of California Irvine
Department
Type
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Dong, H; Courchesne, W (1998) A novel quantitative mating assay for the fungal pathogen Cryptococcus neoformans provides insight into signalling pathways responding to nutrients and temperature. Microbiology 144 ( Pt 6):1691-7
Hristova, K; White, S H (1998) Determination of the hydrocarbon core structure of fluid dioleoylphosphocholine (DOPC) bilayers by x-ray diffraction using specific bromination of the double-bonds: effect of hydration. Biophys J 74:2419-33
Wimley, W C; Hristova, K; Ladokhin, A S et al. (1998) Folding of beta-sheet membrane proteins: a hydrophobic hexapeptide model. J Mol Biol 277:1091-110
Belay, T; Cherniak, R; Kozel, T R et al. (1997) Reactivity patterns and epitope specificities of anti-Cryptococcus neoformans monoclonal antibodies by enzyme-linked immunosorbent assay and dot enzyme assay. Infect Immun 65:718-28
Hristova, K; Selsted, M E; White, S H (1997) Critical role of lipid composition in membrane permeabilization by rabbit neutrophil defensins. J Biol Chem 272:24224-33
Savoy, A C; Lupan, D M; Manalo, P B et al. (1997) Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis. Infect Immun 65:1800-7
Selsted, M E (1997) HPLC methods for purification of antimicrobial peptides. Methods Mol Biol 78:17-33
Belay, T; Cherniak, R; O'Neill, E B et al. (1996) Serotyping of Cryptococcus neoformans by dot enzyme assay. J Clin Microbiol 34:466-70
Hristova, K; Selsted, M E; White, S H (1996) Interactions of monomeric rabbit neutrophil defensins with bilayers: comparison with dimeric human defensin HNP-2. Biochemistry 35:11888-94
Kozel, T R (1996) Activation of the complement system by pathogenic fungi. Clin Microbiol Rev 9:34-46

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