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Eukaryotic Cell doi:10.1128/EC.00318-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Genome-wide transcriptional profiling of the cyclic AMP-dependent signaling pathway during morphogenic transitions of Candida albicans

Microbiology and Molecular Pathogenesis Program, Dartmouth Medical School, Hanover, NH, The Ohio State University, Columbus, Ohio, Department of Bioinformatics and Life Science, Soongsil University, Seoul, Korea and Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon

^* To whom correspondence should be addressed. Email: Paula.Sundstrom{at}Dartmouth.edu.

	Abstract

Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis as well as superficial mucosal candidiasis. In response to the host environment, C. albicans transitions between yeast and hyphal forms. In particular, hyphal growth is important in facilitating adhesion and invasion of host tissues, concomitant with expression of various hyphae-specific virulence factors. In previous work, we showed that the cAMP-signaling pathway plays a crucial role in morphogenic transitions and virulence of C. albicans by studying genes encoding adenylate cyclase-associated protein (CAP1) and high affinity phosphodiesterase (PDE2). However, little is known about the downstream targets of the cAMP-signaling pathway that are responsible for morphological transitions and expression of virulence factors. Here, microarrays were probed with RNA from strains with hypoactive (cap1/cap1 null mutant), hyperactive (pde2/pde2 null mutant), and WT cAMP signaling pathways that would provide insight into the molecular mechanisms of virulence that are regulated by cAMP and are related to morphogenesis of C. albicans. Genes controlling metabolic specialization, cell wall structure, ergosterol/lipid biosynthesis, and stress responses were modulated by cAMP during hypha formation. Phenotypic traits predicted to be regulated by cAMP from the profiling results correlated with the relative strengths of the mutants when tested for resistance to azoles, heat shock and oxidative/nitrosative stress. The results from this study shed important insights into the role of the cAMP signaling pathway not only in morphogenic transitions of C. albicans, but also for adaptation to stress and for survival during host infections.