Transcript profiling reveals rewiring of iron assimilation gene expression in C andida albicans and C . dubliniensis

Hyphal growth is repressed in C andida albicans and C andida dubliniensis by the transcription factor N rg1. Transcript profiling of a C . dubliniensis NRG1 mutant identified a common group of 28 NRG1 ‐repressed genes in both species, including the hypha‐specific genes HWP1 , ECE1 and the regulator of cell elongation UME6 . Unexpectedly, C . dubliniensis NRG1 was required for wild‐type levels of expression of 10 genes required for iron uptake including seven ferric reductases, SIT1 , FTR1 and RBT5 . However, at alkaline p H and during filamentous growth in 10% serum, most of these genes were highly induced in C . dubliniensis . Conversely, RBT5 , PGA10 , FRE10 and FRP1 did not exhibit induction during hyphal growth when NRG1 is downregulated, indicating that in C . dubliniensis NRG1 is also required for optimal expression of these genes in alkaline environments. In iron‐depleted medium at p H 4.5, reduced growth of the NRG1 mutant relative to wild type was observed; however, growth was restored to wild‐type levels or greater at p H 6.5, indicating that alkaline induction of iron assimilation gene expression could rescue this phenotype. These data indicate that transcriptional control of iron assimilation and pseudohypha formation has been separated in C . albicans , perhaps promoting growth in a wider range of niches.