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Biotinylated Surfome Profiling Identifies Potential Biomarkers for Diagnosis and Therapy of Aspergillus fumigatus Infection.
mSphere ( IF 4.8 ) Pub Date : 2020-08-12 , DOI: 10.1128/msphere.00535-20
Lei-Jie Jia 1 , Thomas Krüger 1 , Matthew G Blango 1 , Ferdinand von Eggeling 2, 3, 4 , Olaf Kniemeyer 5, 6 , Axel A Brakhage 5, 6
Affiliation  

Aspergillus fumigatus is one of the most common airborne molds capable of causing mycoses and allergies in humans. During infection, fungal surface proteins mediate the first contact with the human immune system to evade immune responses or to induce hypersensitivity. Several methods have been established for surface proteomics (surfomics). Biotinylation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of peptides is a particularly efficient method to identify the surface-exposed regions of proteins that potentially mediate interaction with the host. After biotinylation of surface proteins during spore germination, we detected 231 different biotinylated surface proteins (including several well-known proteins such as RodA, CcpA, and DppV; allergens; and heat shock proteins [HSPs]), as well as some previously undescribed surface proteins. The dynamic change of the surface proteome was illustrated by detection of a relatively high number of proteins exclusively at one developmental stage. Using immunofluorescence microscopy, we confirmed the surface localization of several HSPs of the HSP70 family, which may have moonlighting functions. Collectively, by comparing our data with data representative of previously published A. fumigatus surface proteomes, our study generated a comprehensive data set corresponding to the A. fumigatus surfome and uncovered the surface-exposed regions of many proteins on the surface of conidia or hyphae. These surface-exposed regions are candidates for direct interaction with host cells and may represent antigenic epitopes that either induce protective immune responses or mediate immune evasion. Thus, our data sets provided and compiled here represent reasonable immunotherapy and diagnostic targets for future investigations.

中文翻译:

生物素化 Surfome 分析确定了诊断和治疗烟曲霉感染的潜在生物标志物。

烟曲霉是最常见的空气传播霉菌之一,能够引起人类真菌病和过敏。在感染期间,真菌表面蛋白介导与人体免疫系统的第一次接触,以逃避免疫反应或诱发超敏反应。已经建立了几种用于表面蛋白质组学(surfomics)的方法。生物素化结合液相色谱-串联质谱 (LC-MS/MS) 鉴定肽是一种特别有效的方法,用于鉴定可能介导与宿主相互作用的蛋白质的表面暴露区域。在孢子萌发过程中表面蛋白生物素化后,我们检测到 231 种不同的生物素化表面蛋白(包括几种众所周知的蛋白质,如 RodA、CcpA 和 DppV;过敏原;和热休克蛋白 [HSP]),以及一些以前未描述的表面蛋白。表面蛋白质组的动态变化通过仅在一个发育阶段检测到相对大量的蛋白质来说明。使用免疫荧光显微镜,我们证实了 HSP70 家族的几个 HSP 的表面定位,这些 HSP 可能具有月光功能。总的来说,通过将我们的数据与之前发布的代表数据进行比较烟曲霉表面蛋白质组,产生我们的研究相当于一个全面的数据集烟曲霉surfome和发现分生孢子或菌丝的表面上的许多蛋白质的表面暴露的区域。这些暴露于表面的区域是与宿主细胞直接相互作用的候选者,可能代表诱导保护性免疫反应或介导免疫逃避的抗原表位。因此,我们在此提供和汇编的数据集代表了未来研究的合理免疫治疗和诊断目标。
更新日期:2020-08-14
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