GENETIC CONTROL OF C. ALBICANS BIOFILM FORMATION

描述(申请人提供)：白色念珠菌是人类主要的真菌病原体之一，可引起粘膜和深层组织感染。侵袭性白色念珠菌感染的一个重要风险因素是植入的医疗设备的存在，该设备为生物膜的形成提供了表面。生物膜为病原体的生存创造了一个受保护的微环境。这里提出的研究的直接目标是确定控制生物膜形成的关键白色念珠菌基因和调控途径，并向前推进以产生机制洞察力。拟议的研究建立在上一个资助期的进展基础上，该资助期确定了两个生物膜转录调控因子Bcr1和Zap1/Csr1，以及它们的几个功能目标基因。我们现在的主要目标是(1)确定促进生物膜黏附的bcr1调控基因产物之间的相互作用，(2)确定zap1靶基因家族在细胞外基质物质积累中的作用，以及(3)确定新发现的促进酵母细胞黏附的转录调节因子的功能。 公共卫生相关性：存在植入的医疗设备，如静脉导管，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假丝酵母菌在植入设备上生长的机制的理解。这种机械性的理解将允许新的治疗和诊断策略的长期发展。

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.