Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p

Abstract

The human pathogen Candida albicans grows and colonizes sites that can vary markedly in pH. The pH response in C. albicans is governed in part by the Rim101p pathway. In Saccharomyces cerevisiae, Rim101p promotes alkaline responses by repressing expression of NRG1, itself a transcriptional repressor. Our studies reveal that in C. albicans, Rim101p-mediated alkaline adaptation is not through repression of CaNRG1. Furthermore, our studies suggest that Rim101p and Nrg1p act in parallel pathways to regulate hyphal morphogenesis, an important contributor to virulence. To determine the wild-type C. albicans transcriptional response to acidic and alkaline pH, we utilized microarrays and identified 514 pH-responsive genes. Of these, several genes involved in iron acquisition were upregulated at pH 8, suggesting that alkaline pH induces iron starvation. Microarray analysis of rim101-/- cells indicated that Rim101p does not govern transcriptional responses at acidic pH, but does regulate a subset of transcriptional responses at alkaline pH, including the iron acquisition genes. We found that rim101-/- cells are sensitive to iron starvation, which suggests that one important aspect of the Rim101p-dependent alkaline pH response is to adapt to iron starvation conditions.