Analysis of the Candida Albicans Proteome

描述（由申请人提供）： 白色念珠菌是迄今为止最常见的分离出的人类真菌病原体。在口腔中，口咽念珠菌病（OPC）是HIV或AIDS患者发病的重要原因。其他形式的粘膜念珠菌病也常见于不同的患者人群，如婴儿、假牙佩戴者、老年人和抗生素治疗后。唑类衍生物，特别是氟康唑，通常可有效治疗粘膜念珠菌病。然而，耐药性已成为一个重要的临床问题。大规模DNA测序为蛋白质分析提供了重要的序列基础设施。术语“蛋白质组学”是指对细胞、组织或生物体中存在的蛋白质（蛋白质组）进行大规模表征，并且涉及用于解析、鉴定、定量和表征蛋白质的技术以及用于存储、交流和链接所得信息的生物信息学工具的组合应用。本提案的实验设计利用了最近完成的NIDCR资助的白色念珠菌基因组测序项目。后基因组时代为研究宿主-真菌相互作用提供了前所未有的机会。这一建议的具体目标包括：（一）对C。白念珠菌蛋白质组在各种条件下和一个可搜索的蛋白质组图谱和数据库的发展作为真菌社区的资源，ii）分析C。通过蛋白质组学和鉴定涉及多药耐药调控网络的蛋白质来研究白念珠菌唑类耐药。我们希望这些项目将为创建C语言的基本工具奠定基础。白念珠菌研究社区，并提供了一个详细的大规模研究的生物现象（耐药性）具有重要的临床影响。

DESCRIPTION (provided by applicant): Candida albicans is by far the most frequently isolated human mycotic agent. In the oral cavity, oropharyngeal candidiasis (OPC) is a significant cause of morbidity in patients with HIV or AIDS. Other forms of mucosal candidiasis are also frequent in different patient populations such as infants, denture wearers, the elderly, and following antibiotic therapy. Azole derivatives, in particular fluconazole, are generally effective in the treatment of mucosal candidiasis. However, resistance has emerged as an important clinical problem. Large-scale DNA sequencing has provided an important sequence infrastructure for protein analysis. The term "Proteomics" refers to large-scale characterization of the proteins present in a cell, tissue or organism (the proteome) and involves the combined application of techniques to resolve, identify, quantitate and characterize proteins, as well as bioinformatics tools to store, communicate and interlink the resulting information. The experimental design of this proposal takes advantage of the recently completed NIDCR-funded Candida albicans genome sequencing project. The post-genomic era offers unprecedented opportunities to study host-fungal interactions. The specific aims of this proposal include: i) a pilot feasibility study of the analysis of the C. albicans proteome under a wide variety of conditions and development of a searchable proteomic map and database as a resource for the fungal community, ii) analysis of C. albicans azole resistance by proteomics and identification of proteins implicated in the regulatory networks of multidrug resistance. We will expect that these projects will establish the foundations for creating a fundamental tool for the C. albicans research community and for providing a detailed large-scale study of a biological phenomenon (drug resistance) with important clinical repercussions.