NRG1, a repressor of filamentous growth in C.albicans, is down-regulated during filament induction

Abstract

contributed equally to this workIn response to a variety of external signals, the fungal pathogen Candida albicans undergoes a transition between ellipsoidal single cells (blastospores) and ®la-ments composed of elongated cells attached end-toend. Here we identify a DNA-binding protein, Nrg1, that represses ®lamentous growth in Candida probably by acting through the co-repressor Tup1. nrg1 mutant cells are predominantly ®lamentous under non-®lament-inducing conditions and their colony morphology resembles that of tup1 mutants. We also identify two ®lament-speci®c genes, ECE1 and HWP1, whose transcription is repressed by Nrg1 under noninducing conditions. These genes constitute a subset of those under Tup1 control, providing further evidence that Nrg1 acts by recruiting Tup1 to target genes. We show that growth in serum at 37°C, a potent inducer of ®lamentous growth, causes a reduction of NRG1 mRNA, suggesting that ®lamentous growth is induced by the down-regulation of NRG1. Consistent with this idea, expression of NRG1 from a non-regulated promoter partially blocks the induction of ®lamentous growth.

Efficacy of 7‐benzyloxyindole and other halogenated indoles to inhibit Candida albicans biofilm and hyphal formation

“…In detail, small GTPase RAS1 activates cAMP, which promotes the PKA‐mediated activation of transcription factor EFG1 , which in turn regulates hyphae‐specific genes, such as ALS3 , HWP1 , and ECE1 , and thus, modulates hyphal formation (Leberer et al ., 2001). RBT1 (repressed by TUP1 ) encodes cell surface proteins that are regulated by Tup1, which exhibits high similarity to HWP1 (Braun et al ., 2001). Here, we suggest 7‐benzyloxyindole inhibits biofilm formation by modulating Ras‐cAMP‐Efg1 signalling pathway genes ( HWP1 , RBT1 and ECE1 ), which are strongly associated with long‐term hyphal maintenance, and thus, reducing hyphal development.…”

Characterization and Functional Analysis of the Siderophore-Iron Transporter CaArn1p in Candida albicans

“…Interestingly, they found that the expression of CaFTR1 and CaCFL2 was increased by 16-and 61-fold, respectively. They also found significantly elevated levels of expression of these two genes in a strain with a deletion of CaNRG1, which encodes a DNA-binding subunit for the Tup1p-Ssn6p repressor complex (42)(43)(44). This result prompted us to examine whether CaTup1p also regulates the expression of CaARN1.…”

Candida albicansdimorphism as a therapeutic target

“…Less attention has been paid to factors that regulate the hyphal-to-yeast transition, such as the hyphal repressors Nrg1 or Tup1 [31][32][33], or to factors that are important for maintenance or extension of hyphal growth, for example Cln1, Pes1, Eed1 or Ume6 [34][35][36][37][38]. These factors not only govern morphology, but also regulate morphologyassociated genes, for example, HWP1, SOD5, SAP4-6 or ALS3, the expression of which is linked to hyphal growth under most conditions.…”