Candida albicans Zn Cluster Transcription Factors Tac1 and Znc1 Are Activated by Farnesol To Upregulate a Transcriptional Program Including the Multidrug Efflux Pump .

Farnesol, a quorum-sensing molecule, inhibits hyphal formation, affects its biofilm formation and dispersal, and impacts its stress response. Several aspects of farnesol's mechanism of action remain incompletely uncharacterized. Among these are a thorough accounting of the cellular receptors and transporters for farnesol. This work suggests these processes are linked through the Zn cluster transcription factors Tac1 and Znc1 and their induction of the multidrug efflux pump Cdr1. Specifically, we have demonstrated that Tac1 and Znc1 are functionally activated by farnesol through a mechanism that mimics other means of hyperactivation of Zn cluster transcription factors. This is consistent with our observation that many genes acutely induced by farnesol are dependent on , , or both. A related molecule, 1-dodecanol, invokes a similar response, while several other proposed quorum-sensing molecules do not. Tac1 and Znc1 both bind to and upregulate the promoter in response to farnesol. Differences in inducer and DNA binding specificity lead to Tac1 and Znc1 having overlapping, but nonidentical, regulons. Induction of genes by farnesol via Tac1 and Znc1 was inversely related to the level of present in the cell, suggesting a model in which induction of by Tac1 and Znc1 leads to an increase in farnesol efflux. Consistent with this premise, our results show that expression, and its regulation by and , facilitates growth in the presence of high farnesol concentrations in and in certain strains of its close relative, .