In Vivo Genome Profiling of Candidiasis

描述（由申请人提供）： 我们建议分析模式的全基因组基因表达的C。从患者样本（口腔刮擦物和唾液以及阴道刮擦物和分泌物）回收的白色念珠菌，其使用Affyssin基因芯片DNA微阵列技术显示高水平的症状性定殖。C.白色念珠菌很快将被广泛用于表征这种模式真菌病原体在实验室中生长时的分子遗传学特征，以及与毒力相关的特定性状的表达相关的分子遗传学特征，所述特定性状例如酵母和菌丝形态发生、表型转换以及对pH，温度，严重缺乏的是对这些许多潜在的毒力性状/标记中的哪些在体内与有症状的疾病一起表达的理解。体外和体内研究之间缺乏一致性和确认，可能导致实验数据的积累，这些数据可能仅与无症状携带和症状性疾病期间表达的相关发病机制无关。更令人担忧的是，这种对离体实验的依赖很可能无法识别调节和影响感染宿主发病机制的重要因素。这对于像C这样的生物体尤其重要。白色念珠菌，它有一个巨大的和可塑性的基因库，它利用这些基因库来快速适应不断变化的物理环境，无论是在培养中还是在感染期间通过外推。我们的总体目标是了解哪些特质对成功的C。白念珠菌的定殖和侵入脊椎动物宿主，以及在这些不同的粘膜部位的疾病表现中表达了哪些特定的和潜在的独特毒力特征。我们的近期目标是分析C.白色念珠菌是与HIV感染和疾病进展相关的最常见的机会致病菌。

DESCRIPTION (provided by applicant): We propose to analyze patterns of genome-wide gene expression in C. albicans recovered from patient specimens (oral scrapings and saliva and vaginal scrapings and secretions) which display a high level of symptomatic colonization using Affymetrix GeneChip DNA microarray technology. Gene expression profiling of C. albicans will soon be widely used to characterize the molecular genetics of this model fungal pathogen as it grows in the laboratory and in relation to the expression of particular traits associated with virulence, such as yeast and hyphal morphogenesis, phenotypic switching, and response to pH, temperature, stress etc. What is acutely lacking is an understanding of which of these many potential virulence traits/markers are expressed in vivo in conjunction with symptomatic disease. The lack of correspondence and confirmation between in vitro and in vivo studies can potentially result in the accumulation of experimental data that may only be tangentially related to relevant mechanisms of pathogenesis expressed during asyrnptomatic carriage and symptomatic disease. Of greater concern, such a reliance on ex vivo experimentation is likely to fail in identifying important factors which regulate and influence pathogenesis in the infected host. This is particularly significant with respect to an organism like C. albicans, which has a vast and plastic repertoire of genes which it draws upon to rapidly adapt to changing physical environments, both in culture and by extrapolation during infection. Our overall aim is to understand what traits are important for the successful C. albicans' colonization and invasion of its vertebrate host and what particular and potentially unique virulence traits are expressed in disease presentations at these different mucosal sites. Our immediate objective will be to analyze in vivo gene expression profiles of C. albicans, the most common opportunistic pathogen associated with HIV infection and disease progression.