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Genomics Strategies for Antifungal Drug Discovery - From Gene Discovery to Compound Screening

[ Vol. 8 , Issue. 13 ]

Author(s):

Debra Aker Willins, Marco Kessler, Scott S. Walker, Gregory R. Reyes and Guillaume Cottarel   Pages 1137 - 1154 ( 18 )

Abstract:


The use of genomics tools to discover new genes, to decipher pathways or to assign a function to a gene is just beginning to have an impact. Genomics approaches have been applied to both antibacterial and antifungal target discovery in order to identify a new generation of antibiotics. This review discusses genomics approaches for antifungal drug discovery, focusing on the areas of gene discovery, target validation, and compound screening. A variety of methods to identify fungal genes of interest are discussed, as well as methods for obtaining full-length sequences of these genes. One approach is well-suited to organisms having few introns (Candida albicans), and another for organisms with many introns (Aspergillus fumigatus). To validate broad spectrum fungal targets, the yeast Saccharomyces cerevisiae was used as a model system to rapidly identify genes essential for growth and viability of the organism. Validated targets were then exploited for high-throughput compound screening.

Keywords:

antifungal,antibacterial,target validation,fungal genes,bacterial genes

Affiliation:

, , , , Genome Therapeutics Corp.,100 Beaver Street, Waltham, MA 02453, USA



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