Genomic and Genetic Approaches for the Identification of Antifungal Drug Targets

A.   K.   Agarwal; T.      Xu; M.   R.   Jacob; Q.      Feng; X.   C.   Li; L.   A.   Walker; A.   M.   Clark

Abstract

Understanding how novel antifungal compounds work in target cells is useful not only in facilitating the discovery of new drugs but also new tools that can be used for further exploration of the targeted biological pathways and their regulation. Various genomic and genetic technologies have been developed in the model yeast Saccharomyces cerevisiae, and have been successfully used to identify drug target pathways. This review discusses the methods developed for some of these technologies, and how they have been used to evaluate the cellular pathways affected by a variety of therapeutic drugs and inhibitors. The advantages and disadvantages of each method are considered, and new advances are highlighted where applicable. The investigation of the mechanism of action of new antifungal compounds will undoubtedly lead to the development of new antifungal therapies targeting new fungal pathways that are more specific and less toxic than currently available antifungal drugs.

Keywords: Transciptional profiling, chemical-genetic interaction, synthetic-genetic interaction, overexpression screen