Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors.
We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata.
University of Vienna, Max F. Perutz Laboratories, Department of Biochemistry, A-1030 Vienna, Austria.
Andreas
A
Roetzer
Christa
C
Gregori
Ann Marie
AM
Jennings
Jessica
J
Quintin
Dominique
D
Ferrandon
Geraldine
G
Butler
Karl
K
Kuchler
Gustav
G
Ammerer
Christoph
C
Schüller
D000595:Amino Acid Sequence; D000818:Animals; D041221:Candida glabrata / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D009997:Osmotic Pressure; D018085:Regulon; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014774:Virulence; D015003:Yeasts / Q000145:classification / Q000235:genetics
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors