GOF mutations in ZCFs conferring new phenotypes.

The yeast Candida albicans is usually a harmless member of the normal microbiota in healthy persons but is also a major fungal pathogen that can colonize and infect almost every human tissue. A successful adaptation to environmental changes encountered in different host niches requires an appropriate regulation of gene expression. The zinc cluster transcription factors are the largest family of transcriptional regulators in C. albicans and are involved in the control of virtually all aspects of its biology. Under certain circumstances, mutations in these transcription factors that alter their activity and the expression of their target genes confer a selective advantage, which results in the emergence of phenotypically altered variants that are better adapted to new environmental challenges. This review describes how gain-of-function mutations in different zinc cluster transcription factors enable C. albicans to overcome antifungal therapy and to successfully establish itself in specific host niches.