Efg1 and Cas5 Orchestrate Cell Wall Damage Response to Caspofungin in Candida albicans.
Antimicrob Agents Chemother. 2020 Nov 09;:
Authors: Xiong K, Su C, Sun Q, Lu Y
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. Here, through a genetic screen, we report the identification of a second transcription factor Efg1 that is also crucial for proper transcriptional responses to echinocandins. Like CAS5, deletion of EFG1 confers hypersensitivity to caspofungin. Efg1 is required for the induction of CAS5 in response to caspofungin. However, ectopically expressed CAS5 cannot rescue the growth defect of efg1 mutant in caspofungin-containing medium. Deleting EFG1 in the cas5 mutant exacerbates the cell wall stress upon caspofungin addition and renders caspofungin-resistant Candida albicans responsive to treatment. Genome-wide transcription profiling of efg1/efg1 and cas5/cas5 using a RNA-Seq indicates that Efg1 and Cas5 co-regulate numbers of caspofungin-responsive genes expression, but they also independently control some genes induction. We further show that Efg1 interacts with Cas5 by yeast two-hybrid and in vivo immunoprecipitation in the presence or absence of caspofungin. Importantly, Efg1 and Cas5 bind to some caspofungin-responsive genes promoter to coordinately activate their expression. Thus, we demonstrate that Efg1, together with Cas5, controls the transcriptional response to cell wall stress induced by caspofungin.
PMID: 33168610 [PubMed - as supplied by publisher]