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白色念珠菌生物膜的形成与抗氧化能力增强有关。

Candida albicans biofilm formation is associated with increased anti-oxidative capacities.

作者信息

Seneviratne C Jayampath, Wang Yu, Jin Lijian, Abiko Yoshi, Samaranayake Lakshman P

机构信息

Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, PR China.

出版信息

Proteomics. 2008 Jul;8(14):2936-47. doi: 10.1002/pmic.200701097.

Abstract

Candida albicans is a common, opportunistic, human fungal pathogen that causes a variety of mucosal and systemic afflictions. It exists in nature both in the biofilm or the sessile phase, as well as in the free-floating or the planktonic phase. Candida biofilms, in particular, display unique characteristics that confer survival advantages over their planktonic counterparts, such as their recalcitrance to common antifungals. The mechanisms underlying Candida biofilm formation and their attributes are poorly understood. In this study, we used a 2-DE-based approach to characterize the protein markers that are differentially expressed in Candida biofilms in comparison to their planktonic counterparts. Using tandem mass spectrometric analysis, we have identified a significant number of proteins including alkyl hydroperoxide reductase, thioredoxin peroxidase, and thioredoxin involved in oxidative stress defenses that are upregulated in the biofilm phase. These proteomic findings were further confirmed by real-time PCR and lucigenin-based chemiluminescence assays. In addition, we demonstrate that a drug target for the new antifungal agent echinocandin, is abundantly expressed and significantly upregulated in Candida biofilms. Taken together, these data imply that the biofilm mode, Candida, compared with their planktonic counterparts, exhibits traits that can sustain oxidative stress (anti-oxidants), and thereby exert resistance to commonly used antifungals.

摘要

白色念珠菌是一种常见的机会性人类真菌病原体,可导致多种黏膜和全身性疾病。它在自然界中既以生物膜或固着相存在,也以浮游或浮游相存在。特别是念珠菌生物膜表现出独特的特征,使其比浮游形式具有生存优势,例如它们对常见抗真菌药物具有抗性。念珠菌生物膜形成的机制及其特性尚不清楚。在本研究中,我们使用基于二维电泳的方法来表征与浮游形式相比在念珠菌生物膜中差异表达的蛋白质标志物。通过串联质谱分析,我们鉴定了大量蛋白质,包括参与氧化应激防御的烷基过氧化氢还原酶、硫氧还蛋白过氧化物酶和硫氧还蛋白,它们在生物膜相中上调。这些蛋白质组学发现通过实时PCR和基于光泽精的化学发光分析得到进一步证实。此外,我们证明新型抗真菌药物棘白菌素的一个药物靶点在念珠菌生物膜中大量表达且显著上调。综上所述,这些数据表明,与浮游形式相比,念珠菌的生物膜模式表现出能够承受氧化应激(抗氧化剂)的特性,从而对常用抗真菌药物产生抗性。

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