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Eukaryotic Cell, October 2004, p. 1249-1260, Vol. 3, No. 5
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.5.1249-1260.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of Cryptococcus neoformans Temperature-Regulated Genes with a Genomic-DNA Microarray{dagger}

Peter R. Kraus,1 Marie-Josée Boily,1 Steven S. Giles,2 Jason E. Stajich,1 Andria Allen,1 Gary M. Cox,2 Fred S. Dietrich,1 John R. Perfect,2 and Joseph Heitman1,2,3,4*

Departments of Molecular Genetics and Microbiology,1 Medicine,2 Pharmacology and Cancer Biology,3 Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina4

Received 5 May 2004/ Accepted 30 June 2004

The ability to survive and proliferate at 37°C is an essential virulence attribute of pathogenic microorganisms. A partial-genome microarray was used to profile gene expression in the human-pathogenic fungus Cryptococcus neoformans during growth at 37°C. Genes with orthologs involved in stress responses were induced during growth at 37°C, suggesting that a conserved transcriptional program is used by C. neoformans to alter gene expression during stressful conditions. A gene encoding the transcription factor homolog Mga2 was induced at 37°C and found to be important for high-temperature growth. Genes encoding fatty acid biosynthetic enzymes were identified as potential targets of Mga2, suggesting that membrane remodeling is an important component of adaptation to high growth temperatures. mga2{Delta} mutants were extremely sensitive to the ergosterol synthesis inhibitor fluconazole, indicating a coordination of the synthesis of membrane component precursors. Unexpectedly, genes involved in amino acid and pyrimidine biosynthesis were repressed at 37°C, but components of these pathways were found to be required for high-temperature growth. Our findings demonstrate the utility of even partial-genome microarrays for delineating regulatory cascades that contribute to microbial pathogenesis.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Research Dr., Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu.

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

Eukaryotic Cell, October 2004, p. 1249-1260, Vol. 3, No. 5
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.5.1249-1260.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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