CANDIDA GENE EXPRESSION DURING OROPHARYNGEAL INFECTION

描述（由申请人提供）：口咽念珠菌病（OPC）是艾滋病的首批临床表现之一。在向艾滋病发展的过程中，50-95%的HIV阳性个体会发生这种情况，疾病预防控制中心估计艾滋病患者的总体患病率为9-31%。这种感染主要是由白色念珠菌引起的，这是一种可引起粘膜和侵袭性感染的共生真菌。我们的总体目标是了解控制宿主相互作用和促进OPC发病机制的白色念珠菌基因产物。我们将使用一种新的基因表达测定技术，nanoString nCounter RNA测量，来测定广泛使用的小鼠OPC模型感染期间白色念珠菌基因的表达水平。我们的初步结果与先前的患者样本和体外感染基因表达有很好的相关性

DESCRIPTION (provided by applicant): Oropharyngeal candidiasis (OPC) is among the first clinical manifestations of AIDS. It occurs in 50-95% of HIV+ individuals during the progression to AIDS, and overall prevalence among AIDS patients is estimated by the CDC at 9-31%. This infection is caused primarily by Candida albicans, a commensal fungus that can cause mucosal and invasive infections. Our overall objective is to understand the C. albicans gene products that govern host interaction and contribute to pathogenesis of OPC. We will use a new gene expression assay technology, nanoString nCounter RNA measurements, to determine levels of C. albicans gene expression during infection in widely used a murine OPC model. Our preliminary results correlate well with prior patient sample and in vitro infection gene expression data, but also reveal extensive stress-responsive gene expression and rewiring of transcription factor-target gene relationships. Proposed studies focus on two classes of gene products: transcription factors, and surface and secreted proteins. We have chosen transcription factor genes because they are a highly regulated gene set, and their products have been or can be connected to functions through systematic mutant screens, expression profiling, and chromatin immunoprecipitation. We have chosen surface and secreted protein genes because their products are engaged in direct interaction with host cells, and because they present the most accessible therapeutic targets. We will develop a reference dataset that explores expression of these genes, and extend the analysis with functional validation. Our findings will generate new hypotheses and inform choices of genes and pathways that can be pursued by all investigators in the community. Statement of