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反向疫苗学和基于消减基因组学的推定疫苗靶标鉴定用于伯克霍尔德氏菌假单胞菌 Bp1651。

Reverse vaccinology and subtractive genomics-based putative vaccine targets identification for Burkholderia pseudomallei Bp1651.

机构信息

Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, 23200, Khyber Pakhtunkhwa, Pakistan.

Department of Biochemistry, Bahauddin Zakariya University Multan, Punjab, Pakistan.

出版信息

Microb Pathog. 2018 Dec;125:219-229. doi: 10.1016/j.micpath.2018.09.033. Epub 2018 Sep 19.

DOI:10.1016/j.micpath.2018.09.033
PMID:30243554
Abstract

The Burkholderia pseudomallei is a unique bio-threat and causative agent of melioidosis. The B. pseudomallei Bp1651 strain has been isolated from a chronic cystic fibrosis patient. The genome-level DNA sequences information of this strain has recently been published. Unfortunately, there is no commercial vaccine available till date to combat B. pseudomallei infection. The genome-wide prioritization approaches are widely used for the identification of potential therapeutic candidates against pathogens. In the present study, we utilized the recently available annotated genomic information of B. pseudomallei Bp1651 through subtractive genomics and reverse-vaccinology strategies to identify its potential vaccine targets. The analyses identified more than 60 pathogen-specific, human host non-homologous proteins that may prioritize in future studies to investigate therapeutic targets for B. pseudomallei Bp1651. The potential B and T-cells antigenic determinant peptides from these pathogen-specific proteins were cataloged using antigenicity and epitope prediction tools. The analyses unveiled a promising antigenic peptide "FQWEFSLSV" from protein-export membrane protein (SecF) of Bp1651 strain, which was predicted to interact with multiple class I and class II MHC alleles with IC value < 100 nM. The molecular docking analysis verified favorable molecular interaction of this lead antigenic peptide with the ligand-binding pocket residues of HLA A*02:06 human host immune cell surface receptor. This peptide is predicted to be a suitable epitope capable to elicit the cell-mediated immune response against the B. pseudomallei pathogen. The putative epitopes and proteins identified in this study may be promising vaccine targets against Bp1651 as well as other pathogenic strains of B. pseudomallei.

摘要

类鼻疽伯克霍尔德菌是一种独特的生物威胁病原体,也是类鼻疽病的病原体。Bp1651 菌株已从慢性囊性纤维化患者中分离出来。该菌株的全基因组 DNA 序列信息最近已公布。不幸的是,迄今为止,尚无针对 B. pseudomallei 感染的商业疫苗。全基因组优先排序方法广泛用于鉴定针对病原体的潜在治疗候选物。在本研究中,我们利用最近获得的 B. pseudomallei Bp1651 的注释基因组信息,通过消减基因组学和反向疫苗学策略来识别其潜在的疫苗靶标。分析确定了 60 多个病原体特异性、人类宿主非同源蛋白,这些蛋白可能是未来研究的重点,以研究 B. pseudomallei Bp1651 的治疗靶点。使用抗原性和表位预测工具对这些病原体特异性蛋白的潜在 B 细胞和 T 细胞抗原决定簇肽进行了编目。分析揭示了来自 Bp1651 菌株蛋白输出膜蛋白 (SecF)的一种有前途的抗原肽“FQWEFSLSV”,该肽与多个 I 类和 II 类 MHC 等位基因的相互作用预测 IC 值 < 100 nM。分子对接分析验证了该主导抗原肽与 HLA A*02:06 人类宿主免疫细胞表面受体配体结合口袋残基的有利分子相互作用。该肽预测是一种合适的表位,能够引发针对 B. pseudomallei 病原体的细胞介导免疫反应。本研究中鉴定的假定表位和蛋白可能是针对 Bp1651 以及其他致病性类鼻疽伯克霍尔德菌菌株的有希望的疫苗靶标。

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