Genetic control of filamentation in Candida albicans

白色念珠菌丝状形成的遗传控制

• 批准号: 7880318
• 负责人: RONDA J ROLFES
• 金额: $ 0.77万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-14 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880318
• 关键词: Amino Acids; Candida albicans; Cells; Cellular Morphology; Cyclic AMP; DNA Microarray Chip; Development; Environment; Exhibits; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Transcription; Homologous Protein; Human; Human body; Hyphae; Immunocompetent; Immunocompromised Host; Implant; Individual; Infection; Investigation; Life; Link; MAP Kinase Gene; Mating Types; Medical Device; Microbial Biofilms; Molecular; Morphology; Mucous Membrane; Mutate; Mutation; Mycoses; Nature; Nitrogen; Pathogenesis; Pathway interactions; Pattern; Play; Proteins; Purines; Relative (related person); Role; Saccharomyces cerevisiae; Serum; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Starvation; Systemic infection; Temperature; Testing; Virulence; Yeasts; chromatin immunoprecipitation; extracellular; fungus; homeodomain; inorganic phosphate; mouse model; mutant; pathogen; purine; research study; transcription factor

DESCRIPTION (provided by applicant): Candida albicans is an opportunistic fungal pathogen and the major cause of human fungal infections. It resides commensally on the mucosal tissues of the human body in immunocompetent individuals. However, it is also responsible for causing superficial mucosal infections and life-threatening systemic infections, particularly in those who are immunocompromised. The morphology of this fungus changes from a yeast form to pseudohyphae and true hyphae. The transition from the yeast form to the filamentous forms is linked to virulence. C. albicans responds to environmental signals to alter its cell morphology, switching from the yeast form to the filamentous forms (termed the dimorphic transition). A number of factors have been identified that serve as triggers for this transition including pH, temperature, starvation for nitrogen, amino acid levels, and the presence of serum. Understanding how the cell senses and responds to its environment is important in understanding its pathogenesis. We are investigating a transcription factor that, when mutated, blocks the ability of the cell to undergo the dimorphic transition. This mutant also exhibits decreased virulence. We plan to investigate changes in gene expression through northern analysis and micro-array studies. We will identify the target genes through chromatin immunoprecipitation. We will also determine the epistatic relationship between this gene and other genes known to be involved in hyphal formation.

描述（由申请人提供）：白色念珠菌是一种机会性真菌病原体，也是人类真菌感染的主要原因。它驻留在免疫能力个体中人体的粘膜组织上。但是，它也负责引起表面粘膜 感染和威胁生命的全身感染，特别是在那些免疫功能低下的人中。这种真菌的形态从酵母形式变为伪菌和真正的菌丝。从酵母形式到丝状形式的过渡与毒力有关。白色念珠菌对环境信号的反应改变其细胞形态，从酵母形式转变为丝状形式（称为二态过渡）。已经确定了许多因素，这些因素是这种过渡的触发因素，包括pH，温度，氮，氨基酸水平和血清的存在。了解细胞对环境的感觉和响应对于理解其发病机理很重要。我们正在研究一个转录因子，该转录因子在突变时会阻止细胞经历双态转变的能力。这个突变体也显示出降低 毒力。我们计划通过北方分析调查基因表达的变化， 微阵列研究。我们将通过染色质免疫沉淀鉴定靶基因。 我们还将确定该基因与其他已知是的基因之间的上皮关系 参与菌丝形成。