Candida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions

The ability of Candida albicans to respond to diverse environments is critical for its success as a pathogen. The RIM101 pathway controls gene expression and the yeast-to-hyphal transition in C. albicans in response to changes in environmental pH in vitro. In this study, we found that the RIM101 pathway is necessary in vivo for pathogenesis. First, we show that rim101(−)/rim101(−) and rim8(−)/rim8(−) mutants have a significant reduction in virulence using the mouse model of hematogenously disseminated systemic candidiasis. Second, these mutants show a marked reduction in kidney pathology. Third, the rim101(−)/rim101(−) and rim8(−)/rim8(−) mutants show defects in the ability to damage endothelial cells in situ. Finally, we show that an activated allele of RIM101, RIM101-405, is a suppressor of the rim8(−) mutation in vivo as it rescues the virulence, histological, and endothelial damage defects of the rim8(−)/rim8(−) mutant. These results demonstrate that the RIM101 pathway is required for C. albicans virulence in vivo and that the function of Rim8p in pathogenesis is to activate Rim101p.