Defining the role of phosphate metabolism in promoting stress resistance and virulence in fungal pathogens

确定磷酸盐代谢在促进真菌病原体的抗逆性和毒力中的作用

• 批准号: 1810170
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1810170
• 关键词: Defining; role; phosphate; metabolism; promoting

The ability of pathogenic fungi to adapt to stresses encountered within different host niches is essential for virulence. Recently, we have found that phosphate homeostasis, regulated by the Pho4 transcription factor, is vital for the resistance of the fungal pathogen, Candida albicans, to diverse and physiologically important stresses encountered during infection. Furthermore, we have found that many of the stress-sensitive phenotypes exhibited by pho4 delta cells, such as to metal cation and superoxide stresses, relate to the impact of phosphate metabolism on metal homeostasis. As Pho4 is vital for C. albicans pathogenesis, these findings provide new insight into how metabolic adaptation promotes C. albicans survival in the face of host-imposed stresses. However we know little regarding the regulation of Pho4 in C. albicans, or the mechanism(s) by which intracellular phosphate levels impact on metal homeostasis resulting in resistance to diverse stresses. In this project, we will define the regulatory network underlying phosphate acquisition strategies in C. albicans and investigate the mechanisms linking phosphate to metal homeostasis and stress resistance. This is important as our data strongly indicates that perturbation of phosphate acquisition strategies in pathogenic fungi could represent a novel therapeutic strategy to attenuate virulence. The project therefore fits with the BBSRC's strategic research priority of "Basic bioscience underpinning health". We predict that the research outcomes generated in C. albicans can also be transferred onto important plant fungal pathogens. Stress tolerance and metal acquisition strategies are also important virulence determinants in many plant pathogens such as the rice blast fungus Magnaporthe grisea and the corn smut fungus Ustilago maydis. Given the increasing threat to food security by such pathogens this project also applies to the research priority "Agriculture and food security".

病原真菌适应不同宿主生态位内遇到的胁迫的能力对于毒力至关重要。最近，我们发现由 Pho4 转录因子调节的磷酸盐稳态对于真菌病原体白色念珠菌抵抗感染过程中遇到的多种重要的生理应激至关重要。此外，我们发现 pho4 delta 细胞表现出的许多应激敏感表型，例如金属阳离子和超氧化物应激，与磷酸盐代谢对金属稳态的影响有关。由于 Pho4 对于白色念珠菌的发病机制至关重要，这些发现为代谢适应如何促进白色念珠菌在宿主施加的压力下生存提供了新的见解。然而，我们对白色念珠菌中 Pho4 的调节，或细胞内磷酸盐水平影响金属稳态从而产生对不同应激的抵抗力的机制知之甚少。在这个项目中，我们将定义白色念珠菌磷酸盐获取策略的调控网络，并研究磷酸盐与金属稳态和应激抵抗之间的联系机制。这很重要，因为我们的数据强烈表明，病原真菌中磷酸盐获取策略的扰动可能代表一种减弱毒力的新治疗策略。因此，该项目符合BBSRC“支撑健康的基础生物科学”的战略研究重点。我们预测，在白色念珠菌中产生的研究成果也可以转移到重要的植物真菌病原体上。胁迫耐受性和金属获取策略也是许多植物病原体（例如稻瘟病菌 Magnaporthe grisea 和玉米黑粉病菌 Ustilago maydis）的重要毒力决定因素。鉴于此类病原体对粮食安全的威胁日益增加，该项目也适用于“农业和粮食安全”的研究重点。