In Vivo Genome Profiling of Candidiasis

描述(由申请人提供)： 我们建议使用Affymetrix基因芯片DNA微阵列技术分析从患者样本(口腔刮片和唾液以及阴道刮片和分泌物)中提取的白念珠菌全基因组基因表达模式，这些样本显示出高度症状性定植。白念珠菌的基因表达谱将很快被广泛用于描述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，如酵母和菌丝形态发生、表型转换以及对pH、温度、压力等的反应。目前迫切缺乏的是了解这些潜在的毒力性状/标记中的哪些在体内与症状性疾病一起表达。体外和体内研究之间缺乏对应和确认可能会导致实验数据的积累，这些数据可能只与无症状携带者和症状性疾病期间表达的相关发病机制密切相关。更令人担忧的是，这种对体外实验的依赖很可能无法识别调节和影响受感染宿主发病的重要因素。对于像白色念珠菌这样的有机体来说，这一点尤其重要，它拥有大量的可塑性基因库，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征对白念珠菌成功地侵袭其脊椎动物宿主是重要的，以及哪些特殊的和潜在的独特毒力特征在这些不同的粘膜部位表现出来。我们的近期目标将是分析白念珠菌的体内基因表达谱，白念珠菌是与艾滋病毒感染和疾病进展有关的最常见的机会性病原体。

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.