Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans.
Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans.
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DOI：
10.1016/j.fgb.2010.08.010
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发表时间：
2011-03
影响因子：
3
通讯作者：
Brown, Alistair J. P.
中科院分区：
文献类型：
--
作者：
Nicholls, Susan;MacCallum, Donna M.;Kaffarnik, Florian A. R.;Selway, Laura;Peck, Scott C.;Brown, Alistair J. P.
进化上保守的热休克转录因子Hsf1在人类的主要真菌病原体白色念珠菌的热适应中起着核心作用。Hsf1在热休克反应中过度磷酸化，并激活启动子中具有热休克元件（HSEs）的基因的转录，这些基因有助于热适应。然而，Hsf1激活与C.白色念珠菌的毒力尚不清楚，因为该病原体被认为与温血动物专性相关，并且该问题尚未被测试，因为HSF 1对于C.白色念珠菌。在这项研究中，我们证明了HSE调节子在C。白色念珠菌细胞感染肾脏我们还表明，Hsf1的CE2区域是激活所必需的，并且该结构域中特定残基的磷酸化有助于Hsf1的激活。C.缺少该CE2区的白色念珠菌HSF 1突变体是活的。然而，它们不能在热休克时激活含有HSE的基因，并且它们是热敏性的。使用这种HSF1 CE2缺失突变体，我们证明了Hsf1的激活，因此热适应，有助于显着的毒性C。白色念珠菌。
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.
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