title: Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals.
abstract: All organisms have evolved mechanisms that protect them against environmental stress. The major fungal pathogen of humans, Candida albicans, has evolved robust stress responses that protect it against human immune defences and promote its pathogenicity. However, C. albicans is unlikely to be exposed to heat shock as it is obligatorily associated with warm-blooded animals. Therefore, we examined the role of the heat shock transcription factor (Hsf1) in this pathogen. We show that C. albicans expresses an evolutionarily conserved Hsf1 (orf19.4775) that is phosphorylated in response to heat shock, induces transcription via the heat shock element (HSE), contributes to the global transcriptional response to heat shock, and is essential for viability. Why has Hsf1 been conserved in this obligate animal saprophyte? We reasoned that Hsf1 might contribute to medically relevant stress responses. However, this is not the case, as an Hsf1-specific HSE-lacZ reporter is not activated by oxidative, osmotic, weak acid or pH stress. Rather, Hsf1 is required for the expression of essential chaperones in the absence of heat shock (e.g. Hsp104, Hsp90, Hsp70). Furthermore, Hsf1 regulates the expression of HSE-containing genes in response to growth temperature in C. albicans. Therefore, the main role of Hsf1 in this pathogen might be the homeostatic modulation of chaperone levels in response to growth temperature, rather than the activation of acute responses to sudden thermal transitions.
authors.affiliation: Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Aberdeen AB25 2ZD, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Nicholls
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Leach
authors.forename: Claire L
authors.initials: CL
authors.lastname: Priest
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity* / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D050296:Microbial Viability; D018832:Molecular Chaperones / Q000096:biosynthesis; D010766:Phosphorylation; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D018832:Molecular Chaperones; D014157:Transcription Factors