GSE37682
Identification and functional characterization of Rca1, a transcription factor involved in both antifungal susceptibility and host response in Candida albicans
The identification of novel transcription factors associated to antifungal response may allow the discovery of fungal specific targets for new therapeutic strategies. A collection of 241 C. albicans transcriptional regulators mutants was screened for altered susceptibility to fluconazole, caspofungin, amphotericin B, and 5-fluorocytosine. Thirteen of these mutants not yet identified in their role in antifungal response were further investigated, and the function of one of them, mutant for orf19.6102 (RCA1) was characterized by transcriptome analysis. Strand specific RNA sequencing and phenotypic tests assigned Rca1 as the regulator of hyphal formation through the cAMP/PKA signaling pathway and the transcription factor Efg1, but also probably through its interaction with a transcriptional repressor, most likely Tup1. The mechanisms responsible for the high level of resistance to caspofungin and fluconazole observed resulting from Rca1 deletion were investigated. From our observations, we propose that caspofungin resistance was the consequence of the deregulation of cell wall gene expression, and that fluconazole resistance was linked to the modulation of the cAMP/PKA signaling pathway activity. In conclusion, our large-scale screening of a C. albicans transcription factor mutants collection allowed the identification of new effectors of the response to antifungals. The functional characterization of Rca1 assigned this TF and its downstream targets as promising candidates for the development of new therapeutic strategies, as Rca1 influences host sensing, hyphal development, and antifungal response. Overall design: Total RNAs from RCA1 mutant and revertant isolates were extracted in duplicate from exponential growth-phase cultures in YEPD media. Differential expression was resolved by strand specific RNA sequencing.