Role of the Heat Shock Transcription Factor in the Fungal Pathogen Candida albicans

微生物必须对环境的变化做出反应，才能生存下来，而这些环境变化中的许多都被视为压力。例如，许多细胞对温度突然升高（热休克）的反应是制造新的蛋白质来修复热休克造成的损伤。这种类型的反应从细菌到人类都是保守的。真菌白色念珠菌生活在哺乳动物体内。(No在哺乳动物以外的地方发现了白色念珠菌的小生境。大多数时候，这种真菌存在于口腔，肠道或生殖器的粘膜（潮湿）上，相对无害。但是，它可以引起人类疾病。念珠菌引起口腔和阴道鹅口疮，它可以导致危及生命的血流感染的医院病人谁是太生病，以打击微生物感染有效。考虑到它在人体中占据的位置，念珠菌很少会暴露在大的温度波动中，因为我们的体温保持在生理限度内（接近37 ℃）。那么，为什么念珠菌在哺乳动物宿主中的进化过程中保留了热休克反应呢？我们不排除念珠菌可能暴露于不频繁的热休克的可能性。然而，我们建议热休克装置保护念珠菌免受其他环境压力。在这个项目中，我们将通过探索缺乏正常热休克反应的念珠菌突变体是否对它在人类宿主中遇到的压力类型更敏感来测试这个想法。这些包括暴露于人体免疫防御用于对抗微生物感染的氧化应激。我们还将定义念珠菌如何响应热休克，建立什么其他类型的压力诱导热休克样的反应，并测试这是否有助于这种真菌的毒力。该项目将为真菌在感染过程中与人类宿主相互作用的方式提供有价值的新见解，以及对真菌应激反应演变的见解。

Microbes must respond to changes in their environmental if they are to survive, and many of these environmental changes are perceived as a stress. For example, many cells respond to a sudden increase in temperature (a heat shock) by making new proteins that repair the damage caused by the heat shock. This type of response is conserved from bacteria to humans. The fungus Candida albicans lives in mammals. (No niches have been found for Candida albicans other than in mammals.) Most of the time, this fungus exists relatively harmlessly on mucous (damp) membranes in the mouth, intestines or genitalia, for example. However, it can cause human disease. Candida causes oral and vaginal thrush, and it can cause life-threatening bloodstream infections in hospital patients who are too ill to combat microbial infections effectively. Given the sites that it occupies in humans, Candida will rarely be exposed to large temperature fluctuations, because our body temperature is maintained within physiological limits (close to 37C). Why then has Candida retained a heat shock response during its evolution within its mammalian host? We do not exclude the possibility that Candida might be exposed to infrequent heat shocks. However, we propose that the heat shock apparatus protects Candida against other environmental stresses. In this project we will test this idea by exploring whether Candida mutants that lack a normal heat shock response are more sensitive to the types of stress that it encounters in the human host. These include exposure to the oxidative stresses that human immunological defences use to combat microbial infections. We will also define how Candida responds to heat shock, establish what other types of stress induce a heat shock-like response, and test whether this contributes to the virulence of this fungus. This project will provide valuable new insights into the ways in which the fungus interacts with its human host during an infection, as well as insights into the evolution of stress responses in fungi.