Molecular characterisation of fungal environmental carbon dioxide sensing and its integration with cAMP signalling and metabolism.

真菌环境二氧化碳传感的分子特征及其与 cAMP 信号传导和代谢的整合。

• 批准号: BB/F000596/1
• 负责人: Fritz Muhlschlegel
• 金额: $ 49.11万
• 依托单位: University of Kent
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF000596%2F1
• 关键词: Molecular; characterisation; fungal; environmental; carbon

The fungal pathogen Candida albicans is non-virulent in healthy individuals where it is part of the normal skin and intestinal flora. On the contrary, in patients whose immune system is not functional as a consequence of cancer, age, or AIDS, this fungus is a major cause of death. C. albicans undergoes a series of characteristic morphological changes important for its ability to cause damage to the infected host. These changes are controlled by host environmental cues such as the elevated temperature inside the body, the slightly alkaline pH of blood as well as high carbon dioxide concentrations. Inside our body the concentration of carbon dioxide is approximately 150 fold higher than in the air surrounding us. When the fungal pathogen C. albicans senses the higher CO2 inside the host, it initiates a series of morphological changes, which enable it to infect that host. Recently we identified the enzyme from C. albicans responsible for these changes. Now we want to investigate precisely how this enzyme senses CO2. CO2 serves other functions important for the survival of C. albicans. For example it is a fundamental part of basic cellular metabolism. We also propose to study whether the CO2 sensing enzyme is related to C. albicans metabolism. Interfering with fungal CO2 sensing may open up possibilities to better manage C. albicans infection in the future.

真菌病原体白色念珠菌在健康个体中是非毒性的，它是正常皮肤和肠道菌群的一部分。相反，在因癌症、年龄或艾滋病而导致免疫系统功能丧失的患者中，这种真菌是导致死亡的主要原因。白色念珠菌经历一系列特征形态变化，这对其对受感染宿主造成损害的能力很重要。这些变化受宿主环境因素的控制，如体内温度升高、血液pH值偏碱性以及二氧化碳浓度高。我们体内二氧化碳的浓度大约是我们周围空气的150倍。当真菌病原体白色念珠菌感觉到宿主体内较高的二氧化碳时，它会引发一系列形态变化，使其能够感染宿主。最近，我们从白色念珠菌中发现了导致这些变化的酶。现在我们要精确地研究这种酶是如何感知二氧化碳的。二氧化碳对白色念珠菌的生存还有其他重要的作用。例如，它是基本细胞代谢的基本组成部分。我们还建议研究二氧化碳感应酶是否与白色念珠菌的代谢有关。干扰真菌的二氧化碳感应可能会在未来更好地控制白色念珠菌感染。