Candida albicans UPC2 is transcriptionally induced in response to antifungal drugs and anaerobicity through Upc2p-dependent and -independent mechanisms

Many genes in the Candida albicans ergosterol biosynthetic pathway are controlled by the transcriptional activator Upc2p, which is upregulated in the presence of azole drugs and has been suggested to regulate its own transcription by an autoregulatory mechanism. The UPC2 promoter was cloned upstream of a luciferase reporter gene (RLUC). UPC2-RLUC activity was induced in response to ergosterol biosynthesis inhibitors and in response to anaerobicity. Under both conditions, induction correlates with the magnitude of sterol depletion. Azole inducibility in the parental strain was approximately 100-fold, and in a UPC2 homozygous deletion strain was 17-fold, suggesting that, in addition to autoregulation, UPC2 transcription is controlled by a novel, Upc2p-independent mechanism(s). Curiously, basal UPC2-RLUC activity was fivefold higher in the deletion strain, which may be an indirect consequence of the lower sterol level in this strain, or a direct consequence of repression by an autoregulatory mechanism. These results suggest that transcriptional regulation of UPC2 expression is important in the response to antifungal drugs, and that this regulation occurs through Upc2p-dependent as well as novel Upc2p-independent mechanisms.