The transcriptional circuitry controlling biofilm development in Candida albicans

描述(申请人提供)：酵母菌白色念珠菌是人类消化道的正常居民。它也是人类最常见的真菌病原体，可引起黏膜和全身感染，特别是在免疫功能低下的患者中。这项提案试图了解白色念珠菌如何协调生物膜的形成--弹性的、表面相关的、有组织的细胞团。生物膜的形成具有医学意义，因为新的白色念珠菌感染与植入的医疗设备高度相关，这些设备为生物膜的形成提供了有效的底物。我们研究生物膜形成的方法是通过解剖控制这一过程的转录电路。我们的首要目标是了解该回路的单个靶基因如何对生物膜的关键特性做出贡献，如耐药性、细胞间黏附和细胞外基质的产生。 与公共卫生相关：白色念珠菌是人类最常见的真菌病原体。它会在正常人身上引起表面感染，在免疫受损的人中引起危及生命的系统性感染。这项提案试图了解白色念珠菌是如何形成生物膜的，这是一种特别耐机械力和抗真菌药物的细胞群落。白色念珠菌在植入的医疗设备上形成生物膜，是新感染的主要来源。更详细地了解生物膜可能会导致预防和治疗白色念珠菌感染的改进。

DESCRIPTION (provided by applicant): The yeast Candida albicans is a normal resident of the human digestive tract. It is also the most common fungal pathogen of humans, causing both mucosal and systemic infections, particularly in immune compromised patients. This proposal seeks to understand how C. albicans orchestrates the formation of biofilms - resilient, surface- associated, organized groups of cells. Biofilm formation is medically relevant because new C. albicans infections are highly correlated with implanted medical devices, which provide efficient substrates for biofilm formation. Our approach to the study of biofilm formation is through dissection of the transcriptional circuitry that controls this process. Our overarching goal is to understand how the individual target genes of the circuit contribute to the key properties of biofilms, such as drug resistance, cell-cell adhesion, and production of extracellular matrix. PUBLIC HEALTH RELEVANCE: C. albicans is the most prevalent fungal pathogen of humans. It causes superficial infections in normal humans and life threatening, systemic infections in immune compromised individuals. This proposal seeks to understand how C. albicans forms biofilms, communities of cells particularly resistant to mechanical force and antifungal drugs. C. albicans biofilms formed on implanted medical devices and are a major source of new infections. Understanding biofilms in more detail may lead to improvements in preventing and treating C. albicans infections.