[Show abstract][Hide abstract]ABSTRACT: Saccharomyces cerevisiae activates general amino acid control (GCN) in response to amino acid starvation. Some aspects of this response are known to be conserved in other fungi including Candida albicans, the major systemic fungal pathogen of humans. Here, we describe a proteomic comparison of the GCN responses in S. cerevisiae and C. albicans. We have used high-resolution two-dimensional (2-D) gel electrophoresis and peptide mass fingerprinting to develop a 2-D protein map of C. albicans. A total of 391 protein spots, representing 316 open reading frames, were identified. Fifty-five C. albicans and 65 S. cerevisiae proteins were identified that responded reproducibly to 3-aminotriazole (3AT) in a Gcn4p-dependent fashion. The changes in the S. cerevisiae proteome correlated with the response in the S. cerevisiae transcript profile to 3AT treatment (rank correlation coefficient = 0.59; Natarajan et al., Molec. Cell. Biol. 2001, 21, 4347-4368). Significant aspects of the GCN response were conserved in C. albicans and S. cerevisiae. In both fungi, amino acid biosynthetic enzymes on multiple metabolic pathways were induced by 3AT in a Gcn4p-dependent fashion. Carbon metabolism functions were also induced. However, subtle differences were observed between these fungi. For example, purine biosynthetic enzymes were induced in S. cerevisiae, but were not significantly induced in C. albicans. These differences presumably reflect the contrasting niches of these relatively benign and pathogenic yeasts, respectively.