Efg1 is essential for hyphal development in the human pathogen Candida albicans under most conditions. Efg1 is related to basic helix-loop-helix regulators, and therefore most workers presume that Efg1 is a transcription factor. Here we confirm that Efg1 is a DNA binding protein that can interact specifically with the E box.Candida albicans is the major fungal pathogen of humans (19). This fungus causes frequent and recurrent oral and vaginal infections and systemic infections in severely immunocompromised patients. A number of factors are thought to promote establishment and progression of C. albicans infections, including yeast hypha morphogenesis (5,16,20). Several signalling pathways appear to activate hyphal development, and one of these pathways is defined by the factor Efg1 (9, 26). Efg1 probably lies on a Ras-cAMP-protein kinase A signalling pathway (5, 9, 10, 24). Mutations that inactivate Efg1 block hyphal development under most experimental conditions in vitro and in vivo (16,26). For example, C. albicans efg1/efg1 mutants are unable to form hyphae following serum stimulation or pH induction in vitro or in the kidneys of infected animals. However, efg1/efg1 mutants still form hyphae when they are embedded in agar and in some infection models (6, 21). Nevertheless, Efg1 is considered a major morphogenetic regulator in C. albicans (9).Ernst and coworkers pointed out that Efg1 contains a basic helix-loop-helix (bHLH) domain with significant sequence similarity to the APSES family of proteins (9, 26). Members of this family include morphogenetic regulators from other fungi, such as Sok2 and Phd1 from Saccharomyces cerevisiae, Asm1 from Neurospora crassa, and StuA from Aspergillus nidulans. This bHLH domain, which is characteristic of some transcription factors, is thought to promote dimerization and DNA binding (18,22). Therefore, it is generally presumed that Efg1 is a transcription factor, and most models of morphogenetic FIG. 1. Efg1p is required for HYR1 and ALS8 activation during serum-induced morphogenesis. We performed a Northern analysis with isogenic C. albicans strains grown for 2 h in YPD containing 10% fetal calf serum at 37°C; the strains used were wild-type strain SC5314 (WT) (11), cph1/cph1 strain JKC19 (15), efg1/efg1 strain HLC52 (16), and cph1/cph1 efg1/efg1 strain HLC54 (54). ALS8 and HYR1 blots were exposed for 8 h and 4 days, respectively. Data from one of two replicate experiments are shown.
