Polyol homeostasis and virulence in Candida albicans

白色念珠菌的多元醇稳态和毒力

• 批准号: 6760119
• 负责人: Brian Wong
• 金额: $ 29.34万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6760119
• 关键词: Polyol; homeostasis; virulence; Candida; albicans

DESCRIPTION (provided by applicant): Candida albicans produces large amounts of the acyclic polyols D-arabinitol and glycerol, and it accumulates these polyols intracellularly. Polyols function as intracellular osmolytes and stress protectants in other fungi, but their functions in C. albicans are not yet known. Therefore, this project's overall goals are (i) to define the mechanisms by which C. albicans regulates its intracellular polyol concentrations and (ii) to determine if C. albicans' ability to maintain polyol homeostasis is required for wild-type environmental stress tolerance and virulence. The pathway by which C. albicans catabolizes D-arabinitol is known. Therefore, Aim 1 is to elucidate the pathway by which C. albicans synthesizes D-arabinitol and to assess this pathway's functional and pathogenic significance. C. albicans mutants lacking NADPH-dependent D-ribulose reductase will be constructed and tested for D-arabinitol synthesis and catabolism, stress tolerance and virulence. Aim 2 is to elucidate the pathways by which C. albicans synthesizes and catabolizes glycerol and to assess these pathways' significance. The C. albicans homologs of the Saccharomyces cerevisiae glycerol pathway genes GPD1, GPD2, GPP1, GUT1 and GUT2 will be tested for their abilities to complement the corresponding S. cerevisiae mutations. Also, C. albicans mutants lacking these genes will be constructed and tested for glycerol synthesis and catabolism, stress tolerance and virulence. Aim 3 is to determine if the C. albicans homolog of the S. cerevisiae glycerol uptake protein Gup l p transports glycerol and D-arabinitol into the cell and if C. albicans mutants lacking Guplp are stress intolerant and/or hypovirulent. Aim 4 is to identify the plasma membrane protein that regulates efflux of intracellular polyols in C. albicans and to assess this transporter's role in polyol homeostasis, environmental stress tolerance and virulence.

描述（由申请人提供）： 白色念珠菌会产生大量的无环多醇D-阿拉比尼醇和甘油，并在细胞内积累这些多元醇。多元醇在其他真菌中充当细胞内渗透剂和应激保护物，但它们在白色念珠菌中的功能尚不清楚。因此，该项目的总体目标是（i）定义白色念珠菌调节其细胞内多元浓度的机制，并（ii）确定白色念珠菌是否维持多元型稳态的能力是野生型环境胁迫耐受性和毒力的所必需的。众所周知，白色念珠菌分解D-阿拉比尼醇的途径。因此，目标1是阐明白色念珠菌合成D-阿拉宾醇的途径，并评估该途径的功能和致病意义。缺乏NADPH依赖性D-核糖还原酶的白色念珠菌突变体将被构造，并测试D-阿拉比尼曲霉合成和分解代谢，胁迫耐受性和毒力。目的2是阐明白色念珠菌合成和分解甘油的途径，并评估这些途径的重要性。酿酒酵母甘油途径GPD1，GPD2，GPP1，GUT1和GUT2的白色念珠菌同源物的能力将进行测试。同样，缺乏这些基因的白色念珠菌突变体将被构造和测试，以进行甘油合成和分解代谢，胁迫耐受性和毒力。目的3是确定酿酒酵母的白色念珠菌同源物是否将甘油和D-阿拉比尼醇转运到细胞中以及缺乏GEPLP的白色念珠菌突变体是否应激不耐受性和/或过分呼吸液。 AIM 4是确定调节白色念珠菌中细胞内多醇外流的质膜蛋白，并评估该转运蛋白在多元稳态，环境胁迫耐受性和毒力中的作用。