title: Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans.
abstract: The evolutionarily conserved heat shock transcription factor Hsf1 plays a central role in thermal adaptation in the major fungal pathogen of humans, Candida albicans. Hsf1 becomes hyperphosphorylated in response to heat shock and activates the transcription of genes with heat shock elements (HSEs) in their promoters, these genes contributing to thermal adaptation. However, the relevance of Hsf1 activation to C. albicans virulence is not clear as this pathogen is thought to be obligately associated with warm blooded animals, and this issue has not been tested because HSF1 is essential for viability in C. albicans. In this study, we demonstrate that the HSE regulon is active in C. albicans cells infecting the kidney. We also show the CE2 region of Hsf1 is required for activation and that the phosphorylation of specific residues in this domain contributes to Hsf1 activation. C. albicans HSF1 mutants that lack this CE2 region are viable. However, they are unable to activate HSE-containing genes in response to heat shock, and they are thermosensitive. Using this HSF1 CE2 deletion mutant we demonstrate that Hsf1 activation, and hence thermal adaptation, contributes significantly to the virulence of C. albicans.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Nicholls
authors.forename: Donna M
authors.initials: DM
authors.lastname: MacCallum
authors.forename: Florian A R
authors.initials: FA
authors.lastname: Kaffarnik
authors.forename: Laura
authors.initials: L
authors.lastname: Selway
authors.forename: Scott C
authors.initials: SC
authors.lastname: Peck
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000472:pathogenicity*; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015966:Gene Expression Regulation, Fungal; D000076249:Heat Shock Transcription Factors; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D037521:Virulence Factors
references.citation: Med Mycol. 2008 Feb;46(1):1-15
references.pmid: 17852717
references.citation: J Bacteriol. 1996 Oct;178(19):5850-2
references.pmid: 8824643
references.citation: EMBO J. 2001 Jun 15;20(12):3177-86
references.pmid: 11406594
references.citation: Mol Biol Cell. 2002 May;13(5):1608-14
references.pmid: 12006656
references.citation: Med Mycol. 2003 Aug;41(4):331-8
references.pmid: 12964726
references.citation: Curr Opin Microbiol. 2002 Aug;5(4):366-71
references.pmid: 12160854
references.citation: Mol Microbiol. 2009 Nov;74(4):844-61
references.pmid: 19818013
references.citation: Mol Biol Cell. 2006 Feb;17(2):1018-32
references.pmid: 16339080
references.citation: Yeast. 2000 Jan 15;16(1):65-70
references.pmid: 10620776
references.citation: Mol Biol Cell. 2008 Jan;19(1):308-17
references.pmid: 18003976
references.citation: Fungal Genet Biol. 2009 Feb;46(2):210-9
references.pmid: 19032986
references.citation: Science. 1999 Mar 5;283(5407):1535-8
references.pmid: 10066176
references.citation: J Bacteriol. 1999 May;181(10):3058-68
references.pmid: 10322006
references.citation: PLoS Biol. 2007 Mar;5(3):e64
references.pmid: 17311474
references.citation: Mycoses. 2005 May;48(3):151-61
references.pmid: 15842329
references.citation: Mol Biol Cell. 2003 Apr;14(4):1460-7
references.pmid: 12686601
references.citation: Curr Biol. 2009 Apr 28;19(8):621-9
references.pmid: 19327993
references.citation: Eukaryot Cell. 2009 Jun;8(6):806-20
references.pmid: 19395663
references.citation: BMC Evol Biol. 2009 Feb 21;9:44
references.pmid: 19232129
references.citation: Infect Immun. 1995 Nov;63(11):4506-14
references.pmid: 7591093
references.citation: Mol Biol Cell. 2004 Sep;15(9):4179-90
references.pmid: 15229284
references.citation: Curr Opin Microbiol. 2009 Aug;12(4):384-91
references.pmid: 19616469
references.citation: Eukaryot Cell. 2004 Jun;3(3):715-23
references.pmid: 15189992
references.citation: Biochem Biophys Res Commun. 2001 Jul 20;285(3):696-701
references.pmid: 11453649
references.citation: Mol Cell Biol. 2004 May;24(9):3648-59
references.pmid: 15082761
references.citation: J Infect Dis. 2005 Jul 15;192(2):336-43
references.pmid: 15962230
references.citation: Methods Enzymol. 1991;194:3-21
references.pmid: 2005794
references.citation: Mol Biol Cell. 2003 Jan;14(1):214-29
references.pmid: 12529438
references.citation: Mol Cell Biol. 1999 Jan;19(1):402-11
references.pmid: 9858564
references.citation: Fungal Genet Biol. 2009 Apr;46(4):287-98
references.pmid: 19570501
references.citation: Yeast. 1994 Jan;10(1):39-57
references.pmid: 8203151
references.citation: Antimicrob Agents Chemother. 2010 Apr;54(4):1476-83
references.pmid: 20086148
references.citation: Nature. 2009 Jun 4;459(7247):657-62
references.pmid: 19465905
references.citation: Mol Biol Cell. 2004 Feb;15(2):532-42
references.pmid: 14595107
references.citation: Yeast. 2000 Mar 15;16(4):325-7
references.pmid: 10669870
references.citation: Nat Rev Microbiol. 2006 Jun;4(6):435-44
references.pmid: 16710324
references.citation: Mol Cell Biol. 1998 Nov;18(11):6340-52
references.pmid: 9774650
references.citation: Mol Biol Cell. 2005 Oct;16(10):4814-26
references.pmid: 16030247
references.citation: Methods Enzymol. 2002;350:112-31
references.pmid: 12073308
references.citation: Immunology. 1991 Sep;74(1):20-4
references.pmid: 1718852
references.citation: PLoS Biol. 2009 Jun 16;7(6):e1000134
references.pmid: 19547744