Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor.

Calcineurin is a phosphoprotein phosphatase devoted to the transduction of Ca(2+)-signals in eukaryotes. In the human pathogen Candida albicans, calcineurin function is required for cell morphogenesis, azole tolerance, membrane stress responses, survival in serum and virulence in mice. Molecular mechanisms as well as targets downstream C. albicans calcineurin involved in all these processes are still uncharacterized. Here we report the characterization of a C. albicans Crz1 calcineurin-regulated transcription factor using a Saccharomyces cerevisiae crz1Delta defective strain as heterologous host. CaCrz1p fulfils the function of its S. cerevisiae homolog protein to control the expression of several Ca(2+)/calcineurin-responsive genes acting on the CDRE sequence in promoters. In the model yeast, CaCrz1p activity and localization are regulated by calcineurin. Deletion of CRZ1 gene renders C. albicans hypersensitive to alkaline cations and membrane stress conditions, including that elicited by SDS and antifungal azoles. Our findings indicate that CaCrz1p is member of a calcium-regulated pathway required for the maintenance of membrane integrity.