Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.
Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.
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DOI：
10.1371/journal.pone.0032467
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Klipp E
中科院分区：
文献类型：
--
作者：
Leach MD;Tyc KM;Brown AJ;Klipp E
真核细胞已经进化出感知和适应动态环境变化的机制。特别是，适应热损伤对它们的生存至关重要。人类的主要真菌病原体，白色念珠菌，是专性与温血动物，因此占据热缓冲壁龛。然而，在其在宿主中的进化过程中，它保留了真正的热休克反应，而其他应激反应则显着不同。热激反应是C.白色念珠菌。为了了解这种反应对感染的相关性，我们使用综合系统生物学方法探索了热适应的动态调节。本文提出的热调节数学模型已在C.白色念珠菌，描述了热休克转录因子Hsf1和必需的伴侣蛋白Hsp90的动态自动调节。我们已经使用这个模型来表明，热适应系统显示完美的适应，它保留了一个短暂的分子记忆，并在模拟发烧的热转换过程中激活Hsf1。除了解释这种病原体中热休克反应的进化保守性以及这种反应对感染的相关性外，我们的模型还为其他真核细胞中热适应的分析提供了一个平台。
Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.
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