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蛋白质组学作为一种工具,用于在囊性纤维化背景下鉴定针对曲霉属和枝孢属的新靶点。

Proteomics as a Tool to Identify New Targets Against Aspergillus and Scedosporium in the Context of Cystic Fibrosis.

机构信息

Fungal and Bacterial Biomics Research Group, Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940, Leioa, Bizkaia, Spain.

出版信息

Mycopathologia. 2018 Feb;183(1):273-289. doi: 10.1007/s11046-017-0139-3. Epub 2017 May 8.

Abstract

Cystic fibrosis (CF) is a genetic disorder that increases the risk of suffering microbial, including fungal, infections. In this paper, proteomics-based information was collated relating to secreted and cell wall proteins with potential medical applications from the most common filamentous fungi in CF, i.e., Aspergillus and Scedosporium/Lomentospora species. Among the Aspergillus fumigatus secreted allergens, β-1,3-endoglucanase, the alkaline protease 1 (Alp1/oryzin), Asp f 2, Asp f 13/15, chitinase, chitosanase, dipeptidyl-peptidase V (DppV), the metalloprotease Asp f 5, mitogillin/Asp f 1, and thioredoxin reductase receive a special mention. In addition, the antigens β-glucosidase 1, catalase, glucan endo-1,3-β-glucosidase EglC, β-1,3-glucanosyltransferases Gel1 and Gel2, and glutaminase A were also identified in secretomes of other Aspergillus species associated with CF: Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, and Aspergillus terreus. Regarding cell wall proteins, cytochrome P450 and eEF-3 were proposed as diagnostic targets, and alkaline protease 2 (Alp2), Asp f 3 (putative peroxiredoxin pmp20), probable glycosidases Asp f 9/Crf1 and Crf2, GPI-anchored protein Ecm33, β-1,3-glucanosyltransferase Gel4, conidial hydrophobin Hyp1/RodA, and secreted aspartyl protease Pep2 as protective vaccines in A. fumigatus. On the other hand, for Scedosporium/Lomentospora species, the heat shock protein Hsp70 stands out as a relevant secreted and cell wall antigen. Additionally, the secreted aspartyl proteinase and an ortholog of Asp f 13, as well as the cell wall endo-1,3-β-D-glucosidase and 1,3-β-glucanosyl transferase, were also found to be significant proteins. In conclusion, proteins mentioned in this review may be promising candidates for developing innovative diagnostic and therapeutic tools for fungal infections in CF patients.

摘要

囊性纤维化(CF)是一种遗传疾病,会增加感染微生物(包括真菌)的风险。在本文中,我们收集了与 CF 中最常见的丝状真菌(即烟曲霉和枝顶孢属/枝顶孢属物种)相关的具有潜在医学应用的分泌蛋白和细胞壁蛋白的蛋白质组学信息。在烟曲霉分泌的过敏原中,β-1,3-内葡聚糖酶、碱性蛋白酶 1(Alp1/oryzin)、Asp f 2、Asp f 13/15、几丁质酶、壳聚糖酶、二肽基肽酶 V(DppV)、金属蛋白酶 Asp f 5、mitogillin/Asp f 1 和硫氧还蛋白还原酶受到特别关注。此外,β-葡萄糖苷酶 1、过氧化氢酶、葡聚糖内切-1,3-β-葡聚糖酶 EglC、β-1,3-葡聚糖转移酶 Gel1 和 Gel2 以及谷氨酰胺酶 A 也在与 CF 相关的其他曲霉属物种的分泌物中被鉴定出来:黄曲霉、黑曲霉、构巢曲霉和土曲霉。关于细胞壁蛋白,细胞色素 P450 和 eEF-3 被提议作为诊断靶点,而碱性蛋白酶 2(Alp2)、Asp f 3(假定过氧化物酶 pmp20)、可能的糖苷酶 Asp f 9/Crf1 和 Crf2、GPI 锚定蛋白 Ecm33、β-1,3-葡聚糖转移酶 Gel4、分生孢子疏水性蛋白 Hyp1/RodA 和分泌天冬氨酸蛋白酶 Pep2 作为烟曲霉的保护性疫苗。另一方面,对于枝顶孢属/枝顶孢属物种,热休克蛋白 Hsp70 是一种相关的分泌和细胞壁抗原。此外,还发现了分泌天冬氨酸蛋白酶和 Asp f 13 的同源物,以及细胞壁内-1,3-β-D-葡聚糖酶和 1,3-β-葡聚糖转移酶,这些都是重要的蛋白质。总之,本文中提到的蛋白质可能是为 CF 患者的真菌感染开发创新诊断和治疗工具的有前途的候选物。

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