针对五联巴顿氏菌的药物靶点和候选疫苗的硅学鉴定:一种减法蛋白质组学方法

Shabir Ahmad, Hugo Verli
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摘要

背景寄生虫基因和蛋白质序列的可用性为药物靶标鉴定和疫苗开发提供了宝贵的信息。巴顿菌(Bartonella quintana)就是这样一种寄生虫,它是一种革兰氏阴性、细胞内病原体,会导致哺乳动物宿主感染巴顿菌病。目标 尽管在了解其发病机制方面取得了进展,但对五联巴顿菌特有的毒力因子和调控机制的了解仍然有限。方法与结果 为了探索这些方面,我们采用了一种减法蛋白质组学方法来分析昆特巴氏杆菌的蛋白质组。通过减去宿主和寄生虫蛋白质组中的蛋白质,我们发现了一组寄生虫可能特有但宿主却不存在的蛋白质。这项分析表明,在寄生虫的 1197 个蛋白质序列中,有 660 个蛋白质与人类宿主的蛋白质序列是非同源的。利用重要基因数据库(Database of Essential Genes)进行的进一步分析预测出了 159 个重要蛋白质,其中 28 个为病原体所独有,并被预测为潜在的假定靶标。预测靶标的亚细胞定位显示了 13 个细胞质蛋白、8 个膜蛋白、1 个周质粒蛋白和多个定位蛋白。预测了六种膜抗原蛋白的三维结构和 B 细胞表位。KdtA 和 mraY 蛋白有四个 B 细胞表位,lpxB 和 BQ09550 有三个,而 ftsl 和 yidC 蛋白分别有十一个和六个 B 细胞表位。主要结论 这一见解将这些蛋白质列为新的假定靶点,以便进一步研究它们作为候选药物和疫苗的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In silico identification of drug targets and vaccine candidates against Bartonella quintana: a subtractive proteomics approach
BACKGROUND The availability of genes and protein sequences for parasites has provided valuable information for drug target identification and vaccine development. One such parasite is Bartonella quintana, a Gram-negative, intracellular pathogen that causes bartonellosis in mammalian hosts. OBJECTIVE Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to B. quintana. METHODS AND FINDINGS To explore these aspects, we have adopted a subtractive proteomics approach to analyse the proteome of B. quintana. By subtractive proteins between the host and parasite proteome, a set of proteins that are likely unique to the parasite but absent in the host were identified. This analysis revealed that out of the 1197 protein sequences of the parasite, 660 proteins are non-homologous to the human host. Further analysis using the Database of Essential Genes predicted 159 essential proteins, with 28 of these being unique to the pathogen and predicted as potential putative targets. Subcellular localisation of the predicted targets revealed 13 cytoplasmic, eight membranes, one periplasmic, and multiple location proteins. The three-dimensional structure and B cell epitopes of the six membrane antigenic protein were predicted. Four B cell epitopes in KdtA and mraY proteins, three in lpxB and BQ09550, whereas the ftsl and yidC proteins were located with eleven and six B cell epitopes, respectively. MAINS CONCLUSIONS This insight prioritises such proteins as novel putative targets for further investigations on their potential as drug and vaccine candidates.
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