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利用定量时程蛋白质组学阐明白念珠菌在血清适应过程中潜在的毒力因子。

Elucidation of potentially virulent factors of Candida albicans during serum adaptation by using quantitative time-course proteomics.

机构信息

Japan Society for the Promotion of Science, Sakyo-ku, Kyoto 606-8502, Japan; Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

出版信息

J Proteomics. 2013 Oct 8;91:417-29. doi: 10.1016/j.jprot.2013.07.031. Epub 2013 Aug 12.

DOI:10.1016/j.jprot.2013.07.031
PMID:23948566
Abstract

UNLABELLED

Candida albicans is an opportunistic pathogen that causes fatal disease if the host immunity is compromised. The mortality rate of systemic candidiasis is very high; hence, there is a ceaseless demand for novel pharmaceuticals. In this study, quantitative time-course proteomics of C. albicans during adaptation to fetal bovine serum (FBS) is described. Survival in blood is essential for virulence of C. albicans, and a detailed analysis is required. We cultivated C. albicans in FBS for 0-180min, and determined quantitative time-course variations of 1024 proteins in the cultured cells by using a LC-MS/MS system with a long monolithic silica capillary column. Clustering analysis identified FBS-induced proteins associated with detoxification of oxidative species, high-affinity glucose transport, citrate cycle, oxidative phosphorylation, and iron acquisition. Furthermore, we identified possible virulence factors such as orf19.4914.1 (named Blood-induced peptide 1, Blp1). Heterologous expression of BLP1 in Saccharomyces cerevisiae shortened the lag phase and resulted in a pleiotropic stress-tolerance phenotype, indicating a possible role for quick adaptation to a stressful environment. While further experiments are necessary to prove virulence of the identified factors, systematic identification of candidate virulence proteins in this study will lead to profound understanding of virulence of C. albicans.

BIOLOGICAL SIGNIFICANCE

This paper describes time-course proteomics of C. albicans during adaptation to serum, which is an essential process for fatal systemic candidiasis. Using a LC-MS/MS system with a monolithic silica capillary column, we have successfully characterized time-course variations of 1024 proteins. Among them, orf19.4914.1 (Blp1) was identified as a novel pleiotropic stress-tolerance peptide, which could have an important role for virulence of C. albicans.

摘要

未加标签

白色念珠菌是一种机会致病菌,如果宿主免疫力受损,会导致致命疾病。系统性念珠菌病的死亡率非常高;因此,人们对新型药物的需求不断。在本研究中,描述了白色念珠菌适应胎牛血清(FBS)过程中的定量时间过程蛋白质组学。白色念珠菌在血液中存活对于其毒力至关重要,因此需要进行详细分析。我们将白色念珠菌在 FBS 中培养 0-180min,并用 LC-MS/MS 系统结合长整体式硅胶毛细管柱定量测定培养细胞中 1024 种蛋白质的时间过程变化。聚类分析鉴定了与氧化物种解毒、高亲和力葡萄糖转运、柠檬酸循环、氧化磷酸化和铁摄取相关的 FBS 诱导蛋白。此外,我们还鉴定了可能的毒力因子,如 orf19.4914.1(命名为血诱导肽 1,Blp1)。BLP1 在酿酒酵母中的异源表达缩短了迟滞期,并导致多效应激耐受表型,表明其可能在快速适应应激环境中发挥作用。虽然还需要进一步实验来证明鉴定出的因子的毒力,但本研究中对候选毒力蛋白的系统鉴定将深入了解白色念珠菌的毒力。

生物学意义

本文描述了白色念珠菌适应血清过程中的时间过程蛋白质组学,这是致命性系统性念珠菌病的一个重要过程。使用带有整体式硅胶毛细管柱的 LC-MS/MS 系统,我们成功地对 1024 种蛋白质的时间过程变化进行了特征描述。其中,orf19.4914.1(Blp1)被鉴定为一种新型的多效应激耐受肽,它可能对白色念珠菌的毒力具有重要作用。

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