The heat shock response governed by Hsp90 and Hsf1 is necessary for cell survival and virulence in the pathogenic fungus Candida albicans.

UM > Faculty of Health Sciences > DEPARTMENT OF BIOMEDICAL SCIENCES

Status	已發表Published
	The heat shock response governed by Hsp90 and Hsf1 is necessary for cell survival and virulence in the pathogenic fungus Candida albicans.
	Leach, M.; Farrer, R.; Wong, K. H.; Brown, A.; Cowen, L.
	2014-10-15
Source Publication	International Conference On The Hsp90 Chaperone Machine
Abstract	Temperature is a ubiquitous environmental variable which profoundly influences the physiology of living cells. The ability to adapt to temperature fluctuations is necessary for survival in all organisms. Upon exposure to a sub-lethal heat shock in yeast, normal metabolic functions become repressed and the heat shock transcription factor Hsf1 is activated, inducing heat shock proteins (HSPs). Candida albicans, the most prevalent human fungal pathogen, is an opportunistic pathogen that has evolved as a relatively harmless commensal of healthy individuals. Even though C. albicans occupies thermally buffered niches, it has retained the classic heat shock response, activating Hsf1 during slow thermal transitions such as the increases in temperature suffered by febrile patients. Previously, we have shown that the molecular chaperone heat shock protein 90 (Hsp90) interacts with and down-regulates Hsf1 in C. albicans, thereby modulating short term Hsf1-mediated activation of the classic heat shock response. To obtain a global picture of the heat shock response we have performed both RNA-seq and ChIP-seq in the absence and presence of heat shock to determine which genes Hsf1 binds and regulates. As expected, Hsf1 binds to and regulates heat shock proteins necessary for cell survival upon a heat shock. However, a subset of genes required for virulence was also upregulated and bound by Hsf1. These genes are not required for survival at high temperatures, with mutants lacking these genes displaying no growth defect upon heat shock. Our data suggest that Hsf1 is not only essential for regulating genes necessary for cell survival upon heat shock, but also genes required for virulence. Indeed, cells that have received a sub-lethal heat shock are more virulent in a Galleria mellonella model of infection compared to cells grown at 30˚C. Finally, we show that depletion of HSP90 drastically changes the signature of the heat shock response, blocking upregulation of many of these virulence genes. Therefore, Hsf1 and Hsp90 act in concert in the pathogen to combat the host response of fever by upregulating genes necessary for cell survival and continued infection.
Keyword	Heat Shock Hsp90 Virulence Candida Albicans pathogen
Language	英語English
The Source to Article	PB_Publication
PUB ID	13867
Document Type	Conference paper
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences
Corresponding Author	Cowen, L.
Recommended Citation GB/T 7714	Leach, M.,Farrer, R.,Wong, K. H.,et al. The heat shock response governed by Hsp90 and Hsf1 is necessary for cell survival and virulence in the pathogenic fungus Candida albicans.[C], 2014.
APA	Leach, M.., Farrer, R.., Wong, K. H.., Brown, A.., & Cowen, L. (2014). The heat shock response governed by Hsp90 and Hsf1 is necessary for cell survival and virulence in the pathogenic fungus Candida albicans.. International Conference On The Hsp90 Chaperone Machine.

Files in This Item:
There are no files associated with this item.

If you have any objections to this item, please fill out the form below and the administrator will contact you as soon as possible.
Content:
Email：	*
Affiliation No.
Verification Code:	Refresh

Any comments and suggestions are welcomed.
Title:	*
Content:
Email：	*
Verification Code:	Refresh