Pseudohyphal Regulation by the Transcription Factor Rfg1p in Candida albicans

The opportunistic human fungal pathogen Candida albicans is a major cause of nosocomial infections. One of the fundamental features of C. albicans pathogenesis is the yeast-to-hypha transition. Hypha formation is controlled positively by transcription factors such as Efg1p and Cph1p, which are required for hyphal growth, and negatively by Tup1p, Rfg1p, and Nrg1p. Previous work by our group has shown that modulating NRG1 gene expression, hence altering morphology, is intimately linked to the capacity of C. albicans to cause disease. To further dissect these virulence mechanisms, we employed the same strategy to analyze the role of Rfg1p in filamentation and virulence. Studies using a tet-RFG1 strain revealed that RFG1 overexpression does not inhibit hypha formation in vitro or in the mouse model of hematogenously disseminated candidiasis. Interestingly, RFG1 overexpression drives formation of pseudohyphae under yeast growth conditions—a phenotype similar to that of C. albicans strains with mutations in one of several mitotic regulatory genes. Complementation assays and real-time PCR analysis indicate that, although the morphology of the tet-RFG1 strain resembles that of the mitotic regulator mutants, Rfg1p overexpression does not impact expression of these genes.