Analysis of the Candida Albicans Proteome

描述(由申请人提供)： 到目前为止，白色念珠菌是最常见的人类真菌。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在不同的患者群体中也很常见，如婴儿、假牙佩戴者、老年人和抗生素治疗后的患者。唑衍生物，特别是氟康唑，通常在治疗粘膜念珠菌病方面有效。然而，耐药性已经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。蛋白质组学“一词是指对细胞、组织或生物体(蛋白质组)中存在的蛋白质进行大规模表征，涉及综合应用各种技术来分解、鉴定、量化和表征蛋白质，以及利用生物信息学工具来存储、交流和链接所产生的信息。该方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寄主与真菌的相互作用提供了前所未有的机会。这项建议的具体目标包括：i)在各种条件下对白色念珠菌蛋白质组进行分析的试点可行性研究，并开发可搜索的蛋白质组图和数据库，作为真菌社区的资源；ii)通过蛋白质组学分析白色念珠菌的唑类耐药性，并确定与多重耐药性调控网络有关的蛋白质。我们期望这些项目将为白念珠菌研究界建立一个基本工具，并为具有重要临床影响的生物现象(抗药性)提供详细的大规模研究奠定基础。

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.