Efg1 and Cas5 Orchestrate Cell Wall Damage Response to Caspofungin in Candida albicans.

Echinocandins are recommended as the first-line drugs for the treatment of systemic candidiasis. Cas5 is a key transcription factor involved in the response to cell wall damage induced by echinocandins. In this study, through a genetic screen, we identified a second transcription factor, Efg1, that is also crucial for proper transcriptional responses to echinocandins. Like , deletion of confers hypersensitivity to caspofungin. Efg1 is required for the induction of in response to caspofungin. However, ectopically expressed cannot rescue the growth defect of mutant in caspofungin-containing medium. Deleting in the mutant exacerbates the cell wall stress upon caspofungin addition and renders caspofungin-resistant responsive to treatment. Genome-wide transcription profiling of and using transcriptome sequencing (RNA-Seq) indicates that Efg1 and Cas5 coregulate caspofungin-responsive gene expression, but they also independently control induction of some genes. We further show that Efg1 interacts with Cas5 by yeast two-hybrid and immunoprecipitation in the presence or absence of caspofungin. Importantly, Efg1 and Cas5 bind to some caspofungin-responsive gene promoters to coordinately activate their expression. Thus, we demonstrate that Efg1, together with Cas5, controls the transcriptional response to cell wall stress induced by caspofungin.