Genetic control of filamentation in Candida albicans

白色念珠菌丝状形成的遗传控制

• 批准号: 7439177
• 负责人: RONDA J ROLFES
• 金额: $ 7.61万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7439177
• 关键词: Amino Acids; Candida albicans; Cells; Cellular Morphology; Condition; Cyclic AMP; DNA Microarray Chip; DNA Microarray format; 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; Numbers; 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（由申请方提供）：白色念珠菌是一种机会性真菌病原体，是人类真菌感染的主要原因。在免疫活性个体中，它寄生于人体的粘膜组织上。然而，它也是造成浅表粘膜 感染和危及生命的全身性感染，特别是免疫功能低下的患者。这种真菌的形态从酵母菌变为假菌丝和真菌丝。从酵母形式到丝状形式的转变与毒力有关。C.白色念珠菌对环境信号作出反应，改变其细胞形态，从酵母形态转变为丝状形态（称为二态转变）。已经确定了许多因素作为这种转变的触发因素，包括pH值，温度，氮饥饿，氨基酸水平和血清的存在。了解细胞如何感知和响应其环境对于理解其发病机制非常重要。我们正在研究一种转录因子，当突变时，它会阻止细胞进行二态转化的能力。这种突变体也表现出减少 毒力。我们计划通过北方分析研究基因表达的变化， 微阵列研究。我们将通过染色质免疫沉淀来鉴定靶基因。 我们还将确定该基因与其他已知基因之间的上位关系。 参与菌丝的形成。