Antifungal compounds exert their activity through a variety of mechanisms, some of which are poorly understood. Novel approaches to characterize the mechanism of action of antifungal agents will be of great use in the antifungal drug development process. The aim of the present study was to investigate the changes in the gene expression profile of @entity375 following exposure to representatives of the four currently available classes of antifungal agents used in the management of systemic @entity364 . Microarray analysis indicated differential expression of 0.8, 4.1, 3.0, and 2.6% of the genes represented on the Affymetrix S98 @entity375 gene array in response to @entity3102 , @entity2379 , @entity11794 , and @entity4895 ( @entity10498 ), respectively. Quantitative real time reverse transcriptase-PCR was used to confirm the microarray analyses. Genes responsive to @entity3102 , @entity11794 , and 5-FC were indicative of the drug-specific effects. @entity3102 exposure primarily affected genes involved in @entity12364 biosynthesis and @entity5068 uptake; @entity11794 exposure affected genes involved in cell wall integrity; and 5-FC affected genes involved in DNA and protein synthesis, DNA damage repair, and cell cycle control. In contrast, @entity2379 elicited changes in gene expression reflecting cell stress, membrane reconstruction, transport, @entity1391 uptake, and cell wall integrity. Genes with the greatest specificity for a particular drug were grouped together as drug-specific genes, whereas genes with a lack of drug specificity were also identified. Taken together, these data shed new light on the mechanisms of action of these classes of antifungal agents and demonstrate the potential utility of gene expression profiling in antifungal drug development.

Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in XXXX .

@entity12364 :: ('MESH:D004875', 'Chemical') :: ['ergosterol'] @entity2379 :: ('MESH:D000666', 'Chemical') :: ['amphotericin B'] @entity10498 :: ('CHEBI:5100', 'Chemical') :: ['5-FC'] @entity3102 :: ('MESH:D007654', 'Chemical') :: ['ketoconazole', 'Ketoconazole'] @entity4895 :: ('MESH:D005437', 'Chemical') :: ['5-fluorocytosine'] @entity364 :: ('MESH:D009181', 'Disease') :: ['fungal infections'] @entity1391 :: ('CHEBI:26020', 'Chemical') :: ['phosphate'] @entity5068 :: ('CHEBI:15889', 'Chemical') :: ['sterol'] @entity375 :: ('4932', 'Species') :: ['yeast', 'Saccharomyces cerevisiae'] @entity11794 :: ('MESH:C105417', 'Chemical') :: ['caspofungin']
@entity375 :: (4932,Species) :: ['Saccharomyces cerevisiae']
