Genomics strategies for antifungal drug discovery--from gene discovery to compound screening.
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.
Willins
Debra Aker
DA
Genome Therapeutics Corp, 100 Beaver Street, Waltham, MA 02453, USA.
Kessler
Marco
M
Walker
Scott S
SS
Reyes
Gregory R
GR
Cottarel
Guillaume
G
D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000235:genetics; D002176:Candida albicans / Q000235:genetics; D015195:Drug Design; D015723:Gene Library; D016681:Genome, Fungal; D023281:Genomics; D012441:Saccharomyces cerevisiae / Q000235:genetics
D000935:Antifungal Agents