Research Project
2073188
Fungal pathogens are responsible for a variety of diseases ranging from innocuous dermal mycoses to life-threatening systemic infections. In recent years the number of serious fungal infections has increased markedly as a result of the growing number of immunosuppressed and immunocompromised individuals, such as AIDS patients, transplant recipients, and chemotherapy or radiotherapy patients. Efficacious and non-toxic antifungal therapeutics are difficult to identify, in part due to the fact that both humans and fungi are eukaryotes and share many potential molecular targets in common. Most antifungals currently used act against a limited number of targets found primarily on the fungal cell surface. An urgent need exists for more antifungal agents, especially those acting against additional targets. Translation-targeted therapeutics are particularly desirable because of their proven value in treating bacterial infections. This proposal describes a novel high- throughput screen for identifying new antifungal agents specifically targeted against protein translation. The assay identifies translational inhibitors by their ability to stimulate the growth of a specially- designed test fungus on an indicator medium. Secondary assays are used to verify specificity for fungal translation and to determine toxicity to human cells. Preliminary results with purified compounds of known activity support the proposal.
