Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray.
The ability to survive and proliferate at 37 degrees 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 degrees C. Genes with orthologs involved in stress responses were induced during growth at 37 degrees 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 degrees 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. mga2Delta 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 degrees 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.
Department of Molecular Genetics and Microbiology, 322 CARL Building, Box 3546, Research Dr., Duke University Medical Center, Durham, NC 27710, USA.
Peter R
PR
Kraus
Marie-Josée
MJ
Boily
Steven S
SS
Giles
Jason E
JE
Stajich
Andria
A
Allen
Gary M
GM
Cox
Fred S
FS
Dietrich
John R
JR
Perfect
Joseph
J
Heitman
D003455:Cryptococcus neoformans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016681:Genome, Fungal; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
D005656:Fungal Proteins; D014157:Transcription Factors