Genomic profiling of the response of Candida albicans to itraconazole treatment using a DNA microarray

The application of genome-wide expression profiling to determine how drugs achieve their therapeutic effect has provided the pharmaceutical industry w ith an exciting new tool for drug mode-of-action studies. We used DNA chip technology to study cellular responses to perturbations of ergosterol biosy nthesis caused by the broad-spectrum antifungal agent itraconazole. Simulta neous examination of over 6,600 Candida albicans gene transcript levels, re presenting the entire genome, upon treatment of cells with 10 muM itraconaz ole revealed that 296 genes were responsive, For 116 genes transcript level s were decreased at least 2.5-fold, while for 180 transcript levels were si milarly increased. A global upregulation of ERG genes in response to azole treatment was observed. ERG11 and ERGS were found to be upregulated approxi mately 12-fold, In addition, a significant upregulation was observed for ER G6, ERG1, ERG3, ERG4, ERG10, ERG9, ERG26, ERG25, ERC2, IDII, HMGS, NCP1, an d FEN2, all of which are genes known to be involved in ergosterol biosynthe sis, The effects of itraconazole on a wide variety of known metabolic proce sses are discussed, As over 140 proteins with unknown function were respons ive to itraconazole, our analysis might provide-in combination with phenoty pic data-first hints of their potential function. The present report is the first to describe the application of DNA chip technology to study the resp onse of a major human fungal pathogen to drug treatment.