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
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
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.
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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Copyright © 2004 by the American Society for Microbiology.