The occurrence of fungal infections has escalated significantly in recent years and is expected to continue to increase for the foreseeable future. Unfortunately, only a limited number of antifungal drugs are currently available for use, due in part to a dearth of suitable targets. In this context, the ultimate aim of the proposed investigation is to test the premise that the elongation-like factor protein (Elf1p) will be a useful chemotherapeutic target. Elf1p is attractive for this purpose because there is no known homologue in mammalian cells. Further, in preliminary work, using Candida albicans as a model organism, strains that were disrupted in the ELF1 locus exhibited obvious growth defects in vitro. The aim of the proposed research is to extend the earlier work to: 1) validate Elf1p as an antifungal target in the murine model of systemic candidiasis; 2) develop high throughput assays for Elf1p activity; and 3) begin screening natural product libraries for novel inhibitors against Elf1p. PROPOSED COMMERCIAL APPLICATION: Successful identification of new chemotherapeutic agents for the treatment of deep-seated fungal infections would have a major impact on the physician's ability to effectively care for patients suffering from systemic mycosis.
Thesaurus Terms: Candida albicans, antifungal agent, biological product, candidiasis, drug design /synthesis /production, drug discovery /isolation, transcription factor genetic strain, virulence laboratory mouse, molecular cloning, spectrometry
