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

Abstract

Hyphal growth is repressed in Candida albicans and C. dubliniensis by the transcription factor Nrg1. 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 7 ferric reductases, SIT1, FTR1 and RBT5. However, at alkaline pH 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 pH4.5, reduced growth of the NRG1 mutant relative to wild-type was observed, however growth was restored to wild-type levels or greater at pH 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 have been separated in C. albicans, perhaps promoting growth in a wider range of niches.