Genetic Control of C. albicans Biofilm Formation

白色念珠菌是一种主要的人类真菌病原体，引起粘膜和深部组织感染。一 C.重要风险因素白色念珠菌感染是存在植入的医疗器械， 用于生物膜形成的表面。生物膜为微生物的生存创造了一个受保护的微环境。 病原体本文提出的研究的近期目标是确定关键C。白色念珠菌基因和 控制生物膜形成的调节途径，长期目标是开发新的治疗方法 基于这种理解的战略。我们已经实施了一种新的策略来分析独特的C。 白念珠菌性状：转录因子功能调查。通过这种策略，我们创造出了具有缺陷的菌株， 每个转录因子基因，并测试菌株的表型缺陷。然后我们使用微阵列分析 以鉴定在所研究的表型中具有直接作用的靶基因。到目前为止，我们已经测试了 在84个转录因子基因中的每一个中的纯合插入突变体用于生物膜缺陷。锌指 蛋白Bcr1 β是生物膜形成和一组表面蛋白基因表达所必需的， 粘附素。我们将分析单个和多个靶基因突变体以及过表达菌株， 生物膜形成的测定。此外，我们还将确定其他生物膜调节因子的靶基因， 在我们的屏幕中定义。将对靶基因进行功能分析。最后，我们将测试我们的体外 结果用大鼠中心静脉导管模型在体内形成生物膜。属性包括可行的 将监测负荷、生物膜结构和基因表达谱。

Candida albicans is a major human fungal pathogen, causing both mucosal and deep tissue infections. A significant risk factor for 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, with the long-term objective of developing new treatment strategies based upon this understanding. We have implemented a new strategy for analysis of unique C. albicans traits: a transcription factor function survey. With this strategy, we create strains with defects in each transcription factor gene and test the strains for phenotypic defects. We then use microarray analysis to identify target genes that have a direct role in phenotype under study. We have thus far tested homozygous insertion mutants in each of 84 transcription factor genes for biofilm defects. Zinc-finger protein Bcr1 p is required for biofilm formation and for expression of a group of surface protein genes and adhesins. We will analyze single and multiple target gene mutants as well as overexpressing strains in assays for biofilm formation. In addition, we will identify target genes for additional biofilm regulators that we define in our screen. Target genes will be subjected to functional analysis. Finally, we will test our in vitro results with a rat central venous catheter model for biofilm formation in vivo. Attributes including viable burden, biofilm architecture, and gene expression profiles will be monitored.