. During the last three decades there has been a dramatic increase in the frequency of fungal infections in immunodeficient hosts. Mycoses in compromised hosts are mainly the result of opportunistic infections; species of Cryptococcus, Candida, Aspergillus and Pneumocystis carinii are important causative agents. Current treatments for fungal infections are limited by few therapeutic options. Available drugs include amphotericin B and a variety of azoles. Unfortunately, amphotericin B is toxic to humans and clinical resistance to azoles is increasing. These observations underscore the clear need for new antifungals. Permatins are a family of small proteins found in seeds of plants. Zeamatin, the type family member isolated from corn, causes fungal membrane permeability changes and has potent in vitro fungicidal activity, killing a wide number of human pathogenic fungi. In this Phase I SBIR the PI proposes to test the feasibility of zeamatin as an antifungal therapeutic. First, one gram of zeamatin will be purified to apparent homogeneity. Second, the effect of zeamatin on Pneumocysits carinii in an in vivo infection model will be determined. Third, zeamatin will be tested against the dermatophyte, Trichophyton mentagrophytes var granulare in an in vivo topical infection model.
