The putative transcription factor CaRtg3 is involved in tolerance to cations and antifungal drugs as well as serum-induced filamentation in Candida albicans.

The activated retrograde (RTG) pathway controls transcription of target genes through a heterodimer of transcription factors, Rtg1 and Rtg3, in Saccharomyces cerevisiae. Here, we have identified the sole homologous gene CaRTG3 that encodes a protein of 520 amino acids with characteristics of the basic helix-loop-helix/leucine zipper (bHLH/Zip) family in Candida albicans. Deletion of CaRTG3 results in C. albicans cells being sensitive to high concentrations of calcium and lithium cations as well as sodium dodecyl sulfate and activates the calcium/calcineurin signaling pathway in C. albicans cells. CaRTG3 is also involved in the tolerance of C. albicans cells to the antifungal drugs azoles and terbinafine, but not to the antifungal drugs casponfungin and amphotericin B as well as the cell-wall-damaging reagents Calcoflour White and Congo red. In contrast to ScRtg3, CaRtg3 is not involved in the osmolar response and is constitutively localized in the nucleus. However, deletion of CaRTG3 results in a delay in serum-induced filamentation of C. albicans cells. Therefore, CaRtg3 plays a role in tolerance to cations and antifungal drugs as well as serum-induced filamentation in C. albicans.