Determining Antifungal Target Sites in the Sterol Pathway of the Yeast Candida and Saccharomyces

摘要

Resistance to antifungal drugs is a major reason for the increase in fungal infections. Coupled with medical advances which allow access to pathogens and chemotherapies and diseases which reduce the efficacy of the immune system, the have future scenario predicts that prospects will worsen unless we are able to replenish our arsenal of effective antifungal compounds. This problem is important in both life-threatening, systemic infections as well as in topical infections which lead to significant losses in work-place productivity. The work reported here seeks to identify new target sites in the sterol biosynthetic pathway against which new antifungal compounds might be developed. The ERG6 gene has been disrupted in Candida albicans, a human pathogen, and sensitivity of the disrupted strain to a variety of antifungals and cellular inhibitors has indicated that ERG6p inhibitors would be effective antifungals especially in combination with other compounds. The ERG25 gene from C. albicans has been sequenced and a disruption system has been devised to characterize this gene as a potential site. The ERG26 gene from C. albicans has been cloned and the final gene, the presumptive ERG27, has been cloned in Saccharomyces cerevisiae as a prelude to characterization in C. albicans.