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基于多表位的表皮葡萄球菌疫苗设计:一种消减蛋白质组学和免疫信息学方法。

Multi-epitope based vaccine design against Staphylococcus epidermidis: A subtractive proteomics and immunoinformatics approach.

作者信息

Sethi Guneswar, Sethi Satyanarayan, Krishna Ramadas

机构信息

Department of Bioinformatics, Pondicherry University, Puducherry, 605014, India.

Central Institute of Freshwater Aquaculture, Research Institute, Bhubaneswar, 751002, India.

出版信息

Microb Pathog. 2022 Apr;165:105484. doi: 10.1016/j.micpath.2022.105484. Epub 2022 Mar 14.

Abstract

Staphylococcus epidermidis has emerged as a major contributor of nosocomial infections across the world. With the increased rate of emerging resistant and previously undefined infectious diseases, there is a growing need to develop a novel vaccine possessing required immunogenic properties. The adopted reverse vaccinology approach identified "IMPNQILTI" of LysM domain protein, "YSYTYTIDA" of staphylococcal secretory antigen SsaA, and "YNYDANTGQ" neutral metalloproteinaseas potential peptides for vaccine design. The 9-mer epitope of target proteins is antigenic, virulent, surface-exposed, non-allergenic, and conserved across various strains of S. epidermidis. Protein-protein interactions study indicated the involvement of target proteins in major biological pathways for S. epidermidis pathogenesis. Protein-peptide docking was performed, and population coverage analysis showed significant interactions of T-cell epitopes with the HLA-binding molecules while covering 90.58% of the world's population. Further, a multi-epitope vaccine of 177 amino acids long was constructed. Docking with Toll-like receptor (TLR-2) molecule confirmed the effective interaction of the vaccine with the receptor. The vaccine efficiency in generating an effective immune response in the host was evaluated by immune simulation. Finally, in silico cloning confirmed that the constructed vaccine can be efficiently expressed in E. coli. However, the designed vaccine needs experimental validation to determine the effectiveness and immunogenicity profile, which will ensure an active immunity against S. epidermidis.

摘要

表皮葡萄球菌已成为全球医院感染的主要致病菌。随着新出现的耐药性和先前未明确的传染病发病率上升,开发一种具有所需免疫原性的新型疫苗的需求日益增长。采用的反向疫苗学方法确定了LysM结构域蛋白的“IMPNQILTI”、葡萄球菌分泌抗原SsaA的“YSYTYTIDA”以及中性金属蛋白酶的“YNYDANTGQ”作为疫苗设计的潜在肽段。目标蛋白的9聚体表位具有抗原性、毒性、表面暴露、无致敏性,并且在各种表皮葡萄球菌菌株中保守。蛋白质-蛋白质相互作用研究表明目标蛋白参与了表皮葡萄球菌致病的主要生物学途径。进行了蛋白质-肽对接,群体覆盖分析显示T细胞表位与HLA结合分子有显著相互作用,同时覆盖了世界90.58%的人口。此外,构建了一个长度为177个氨基酸的多表位疫苗。与Toll样受体(TLR-2)分子对接证实了该疫苗与受体的有效相互作用。通过免疫模拟评估了该疫苗在宿主中产生有效免疫反应的效率。最后,计算机克隆证实构建的疫苗可以在大肠杆菌中有效表达。然而,设计的疫苗需要进行实验验证以确定其有效性和免疫原性特征,这将确保对表皮葡萄球菌产生主动免疫。

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