Evidence for Novel pH-Dependent Regulation of Candida albicans Rim101, a Direct Transcriptional Repressor of the Cell Wall β-Glycosidase Phr2

Abstract

ABSTRACT Candida albicans is a commensal fungus of mucosal surfaces that can cause disease in susceptible hosts. One aspect of the success of C. albicans as both a commensal and a pathogen is its ability to adapt to diverse environmental conditions, including dramatic variations in environmental pH. The response to a neutral-to-alkaline pH change is controlled by the Rim101 signal transduction pathway. In neutral-to-alkaline environments, the zinc finger transcription factor Rim101 is activated by the proteolytic removal of an inhibitory C-terminal domain. Upon activation, Rim101 acts to induce alkaline response gene expression and repress acidic response gene expression. Previously, recombinant Rim101 was shown to directly bind to the alkaline-pH-induced gene PHR1 . Here, we demonstrate that endogenous Rim101 also directly binds to the alkaline-pH-repressed gene PHR2 . Furthermore, we find that of the three putative binding sites, only the −124 site and, to a lesser extent, the −51 site play a role in vivo. In C. albicans , the predicted Rim101 binding site was thought to be CCAAGAA, divergent from the GCCAAG site defined in Aspergillus nidulans and Saccharomyces cerevisiae . Our results suggest that the Rim101 binding site in C. albicans is GCCAAGAA, but slight variations are tolerated in a context-dependent fashion. Finally, our data suggest that Rim101 activity is governed not only by proteolytic processing but also by an additional mechanism not previously described.