Functional dichotomy for a hyphal repressor in Candida albicans

Nrg1 is a repressor of hypha formation and hypha-associated gene expression in the fungal pathogen Candida albicans. It has been well studied in the genetic background of the type strain SC5314. Here we tested Nrg1 function in four other diverse clinical isolates through analysis of nrg1 mutants with SC5314 included as a control. In three strains, nrg1 mutants unexpectedly produced aberrant hyphae under inducing conditions, as assayed by microscopic observation and endothelial cell damage. The nrg1 mutant of strain P57055 had the most severe defect. We examined gene expression features under hypha-inducing conditions by RNA-Seq for the P57055 and SC5314 backgrounds. The nrg1 mutant of strain P57055 had reduced expression of several hypha-associated genes, including IRF1, RAS2, and ECE1, whereas the nrg1 mutant of strain SC5314 did not. These findings indicate that Nrg1 has a positive role in hypha-associated gene expression in strain P57055. Remarkably, the same hypha-associated genes affected by the nrg1 mutation were also naturally expressed at lower levels in P57055 than in SC5314. Our results suggest that strain P57055 is defective in a pathway that acts in parallel with Nrg1 to upregulate expression of several hypha-associated genes