Identification and characterisation of virulence associated genes during oral infections with Candida albicans

口腔白色念珠菌感染是免疫功能低下患者中非常常见的疾病。本项目的目的是确定与口腔感染相关的真菌因素，并阐明这些因素的相关性和作用。白念珠菌DNA微阵列将用于识别在已建立的口腔念珠菌感染体外模型(RHE)和患者样本中上调或唯一表达的基因。利用RHE模型，我们将剖析几种寄主成分，如上皮细胞、唾液、抗菌肽、白细胞和pH对真菌表达谱的影响。所选基因的表达模式将通过定性表达分析来确定。最后，我们将通过生产零突变菌株和对基因产物的详细分析来分析选定的感染相关基因的相关性和作用。然后，将在RHE模型中分析空突变体，以调查相应基因对PAH发生的影响。在与这一优先项目的其他申请者合作中，我们还将分析宿主在口腔感染期间的反应，并将我们的转录图谱数据与阴道感染的数据进行比较。这些信息不仅有助于了解白色念珠菌是如何致病的，而且还将确定白色念珠菌的因素，如果抑制，可能使我们能够预防口腔感染，并将指出宿主因素对预防口腔念珠菌病至关重要。

Oral infections with Candida albicans are very common diseases in immunocompromised patients. The aim of this project is to identify fungal factors which are associated with oral infection and to elucidate the relevance and role of these factors. C. albicans DNA microarrays will be used to identify genes that are up-regulated or exclusively expressed in an established in vitro model of oral Candida infections (RHE) and in patient samples. Using the RHE model, we will dissect the influence of several host components such as epithelial cells, saliva, antimicrobial peptides, leukocytes and pH on the fungal expression profile. The expression pattern of selected genes will be confirmed by qualitative expression analysis. Finally, we will analyse the relevance and role of selected infection-associated genes by the production of null mutant strains and a detailed analysis of the gene products. Null mutants will then be analysed in the RHE model in order to investigate the impact of the corresponding gene on pat hogenesis. In co-operation with other applicants of this priority programme, we will also analyse the host response during oral infections and compare our transcriptional profiling data with data from vaginal infections. This information will not only help to understand how C. albicans is able to cause disease, but will also identify factors of C. albicans which if suppressed, may enable us to prevent oral infections and will point to host factors crucial for prevention of oral candidosis.