Identification and characterization of virulence associated genes during vaginal infections with Candida albicans, focusing on the cell wall

白色念珠菌是免疫功能低下患者真菌感染的主要原因，但也影响健康个体。在这些感染中，外阴阴道炎（VVC）是最常见的症状性感染之一，影响高达75%的所有妇女。为了了解C.白色念珠菌能够识别、定植和感染阴道，我们希望鉴定C.白色念珠菌感染。阴道念珠菌病毒力相关基因的鉴定将使用念珠菌感染体外重建阴道组织的转录谱进行。这些数据将与口腔和皮肤感染模型的数据进行比较，以揭示阴道组织感染期间特异性表达的基因。这项工作的主要重点将是在感染过程中细胞壁中的蛋白质的功能，因为细胞壁是与宿主相互作用的主要真菌结构。因此，与毒力相关的细胞壁蛋白的功能表征将是第一优先。细胞表面蛋白质已经确定为与毒力在Efg1p依赖的方式将在功能上的特点，在体外以及在小鼠模型的阴道和全身念珠菌病使用突变的方法。在本项目期间收集的结果将直接在来自患者的临床分离株中进行验证，并在本优先计划的进一步应用期间继续进行，以了解C.为临床防治VVC做出贡献。

Candida albicans is the predominant cause of fungal infections in immuno-compromised patients but also affects healthy individuals. Among these infections vulvovaginal Candidiasis (VVC) is one of the most common symptomatic infections, affecting up to 75% of all women. In order to understand how C. albicans is able to recognize, colonize and infect the vaginal tract we want to identify the genes expressed in C. albicans during infection. Identification of virulence associated genes in vaginal candidiasis will be performed using transcriptional profiling of Candida infecting in vitro reconstructed vaginal tissue. These data will be compared to data of oral and cutaneous infection models in a cooperative effort, to reveal genes expressed specifically during infection of vaginal tissue. The major focus of this work will be on the function of the proteins in the cell wall during infection since the cell wall is the primary fungal structure interacting with the host. Thus the functional characterization of cell wall proteins associated with virulence will be of first priority. Cell surface proteins already identified as associated with virulence in an Efg1p dependent manner will be functionally characterized in vitro as well as in mouse models of vaginal and systemic candidiasis using mutational approaches. The results gathered during this project will be verified directly in clinical isolates from patients and continued in further application periods of this priority program in order to understand infection mechanisms of C. albicans and to contribute to prevention and treatment of VVC.