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

Abstract

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.

The Regulatory Proteins Rtg1/3 Govern Sphingolipid Homeostasis in the Human-Associated Yeast Candida albicans

“…Consistent with this notion, the rtg1 as well as the rtg3 deletion mutants showed increased sensitivity to calcium compared to the wild-type reference strain ( Figure S2A). This observation is in agreement with, and provides a basis to, a previous report (Yan et al, 2014).…”

Sfp1 and Rtg3 reciprocally modulate carbon source‐conditional stress adaptation in the pathogenic yeast Candida albicans

“…While this type of intraorganellar communication has not been studied extensively in C. albicans, mitochondrial functionality is known to influence stress resistance in this pathogenic yeast. For example, the inactivation of Goa1 (which is required for respiratory function and localizes to the mitochondrion under stress conditions) or Sam37 (a component of the mitochondrial outer membrane Sorting and Assembly Machinery complex) renders C. albicans cells sensitive to stresses, affects cell wall integrity and attenuates their virulence (Jia et al, 1997;Rothermel et al, 1997;Bambach et al, 2009;Leach et al, 2012c;Qu et al, 2012;Yan et al, 2014). Also the attenuation of mitochondrial functionality by Rtg3 inactivation might reduce the ability of lactate-growing cells to generate the metabolic energy required for stress adaptation.…”

“…1). Rtg3 is a bZIP transcription factor that is thought to be involved in galactose metabolism, cationic stress resistance, antifungal drug resistance and filamentous growth (Inglis et al, 2012;Yan et al, 2014;Dalal et al, 2016). Its orthologue in S. cerevisiae is a downstream effector of the TOR (Target of Rapamycin) pathway, which regulates growth in response to nutrients.…”

RNA sequencing reveals an additional Crz1-binding motif in promoters of its target genes in the human fungal pathogen Candida albicans

“…To measure the UTR2 promoter-driven β-galactosidase activity in the wild type and the crz1/crz1 mutant, we integrated the StuI-linearized plasmids containing the lacZ reporters for CaUTR2 promoter into the RPS1 locus of these strains as described [16,28]. The β-galactosidase activity was determined using the substrate ONPG as described [46,47]. Data are mean ± SD from six independent experiments.…”