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Eukaryotic Cell, December 2007, p. 2376-2390, Vol. 6, No. 12
1535-9778/07/$08.00+0     doi:10.1128/EC.00318-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Genome-Wide Transcriptional Profiling of the Cyclic AMP-Dependent Signaling Pathway during Morphogenic Transitions of Candida albicans ^,

Yong-Sun Bahn,^2, Matthew Molenda,² Janet F. Staab,^2, Courtney A. Lyman,¹ Laura J. Gordon,¹ and Paula Sundstrom^1,2*

Microbiology and Molecular Pathogenesis Program, Dartmouth Medical School, Hanover, New Hampshire,¹ The Ohio State University, Columbus, Ohio²

Received 27 August 2007/ Accepted 1 October 2007

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 the expression of various hypha-specific virulence factors. In previous work, we showed that the cyclic AMP (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) (Y. S. Bahn, J. Staab, and P. Sundstrom, Mol. Microbiol. 50:391-409, 2003; and Y. S. Bahn and P. Sundstrom, J. Bacteriol. 183:3211-3223, 2001). However, little is known about the downstream targets of the cAMP signaling pathway that are responsible for morphological transitions and the expression of virulence factors. Here, microarrays were probed with RNA from strains with hypoactive (cap1/cap1 null mutant), hyperactive (pde2/pde2 null mutant), and wild-type cAMP signaling pathways to provide insight into the molecular mechanisms of virulence that are regulated by cAMP and that are related to the 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 and subjected to heat shock stress and oxidative/nitrosative stress. The results from this study provide 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.

Published ahead of print on 19 October 2007.

Supplemental material for this article may be found at http://ec.asm.org/.

Present address: Department of Bioinformatics and Life Science, Soongsil University, Seoul, South Korea 156-743.

Present address: Oregon Health & Science University, Division of Infectious Diseases, 3181 SW Sam Jackson Park Rd., Portland, OR 97239.