Topoisomerases as Target for Antifungal Drug Development

The study's objectives are to establish means to discover agents effective against fungal topoisomeLong-term objectives are to implement a cell-based target-oriented search for inhibitors of topoisomfungi with complementary enzyme-based assays. Towards this effort we will devote our natural productprimarily on natural products from fungi. The test organisms to be used in these assays are the targthe drugs are intended, such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformanspathogens will be manipulated by molecular genetic means to disrupt specific genes so that they becotopoisomerase inhibitors. This study focuses on the C. albicans topoisomerase I. Preliminary studiestopoisomerase I, support the concept that species- specific inhibitors can be detected and that inhiby a DNA-enzyme complex is sufficient in C. albicans to cause cell death. Furthermore, these studiesselective for C. albicans topoisomerase I that does not affect mammalian topoisomerase I can be deteof a broad-scale search using the genetically engineered target-organisms provides an opportunity toan area that is in dire need of new drugs.