GENETIC CONTROL OF C. ALBICANS BIOFILM FORMATION

白色念珠菌生物膜形成的遗传控制

• 批准号: 8072955
• 负责人: AARON P MITCHELL
• 金额: $ 35.26万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8072955
• 关键词: Adherence; Alcohol dehydrogenase; Antibiotics; Antifungal Therapy; Aryl-alcohol dehydrogenase; Bacterial Adhesins; Binding; Biological Assay; Candida; Candida albicans; Catheters; Cells; Chemotherapy-Oncologic Procedure; Development; Diagnostic; Extracellular Matrix; Funding; Gene Family; Gene Targeting; Genes; Genetic; Glucans; Glycoside Hydrolases; Goals; Growth; Human; Implant; In Vitro; Individual; Infection; Measures; Mediating; Medical Device; Membrane Proteins; Microbial Biofilms; Modeling; Oxidoreductase; Pathogenicity; Patients; Peptides; Preventive; Production; Proteins; Rattus; Regulatory Pathway; Research; Risk Factors; Role; Seeds; Sepsis; Source; Surface; Testing; Therapeutic; Tissues; Venous; Yeasts; attributable mortality; base; implantable device; improved; in vivo; insight; microbial community; mutant; novel diagnostics; novel therapeutics; pathogen; programs; prospective; transcription factor

DESCRIPTION (provided by applicant): Candida albicans is among the major human fungal pathogens, causing both mucosal and deep tissue infections. A significant risk factor for invasive C. albicans infection is the presence of an implanted medical device, which provides a surface for biofilm formation. The biofilm creates a protected microenvironment for survival of the pathogen. The immediate goal of studies here proposed is to define the key C. albicans genes and regulatory pathways that govern biofilm formation, and to move forward to yield mechanistic insight. The proposed studies build upon progress in the last funding period that defined two biofilm transcriptional regulators, Bcr1 and Zap1/Csr1, along with several of their functional target genes. Our main objectives now are (1) to define the interactions among Bcr1 regulated gene products that promote biofilm adherence, (2) to determine roles of Zap1 target gene families in accumulation of extracellular matrix material, and (3) to define the functions of newly discovered transcriptional regulators that promote adherence of yeast-form cells PUBLIC HEALTH RELEVANCE: Presence of an implanted medical device, such as a venous catheter, is a major risk factor for lethal disseminated Candida infections. Proposed studies will improve our understanding of mechanisms that permit Candida growth on implanted devices. The mechanistic understanding will permit longer-term development of new therapeutic and diagnostic strategies.

描述（由申请方提供）：白色念珠菌是主要的人类真菌病原体之一，可引起粘膜和深部组织感染。一个重要的危险因素为侵袭性C。白色念珠菌感染是存在植入的医疗装置，其提供用于生物膜形成的表面。生物膜为病原体的生存创造了受保护的微环境。本文提出的研究的近期目标是确定关键C。白念珠菌的基因和调控途径，支配生物膜的形成，并向前迈进，以产生机制的见解。拟议的研究建立在上一个资助期的进展基础上，该研究定义了两种生物膜转录调节因子Bcr 1和Zap 1/Csr 1，沿着它们的几个功能靶基因。我们现在的主要目标是（1）确定Bcr 1调节的基因产物之间的相互作用，促进生物膜粘附，（2）确定Zap 1靶基因家族在细胞外基质物质积累中的作用，和（3）确定新发现的转录调节因子的功能，促进酵母细胞的粘附 公共卫生关系：植入的医疗器械（如静脉导管）的存在是致死性播散性念珠菌感染的主要风险因素。拟议的研究将提高我们对允许念珠菌在植入器械上生长的机制的理解。机制的理解将允许新的治疗和诊断策略的长期发展。