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利用消减蛋白质组学鉴定新型药物靶点和反向疫苗学开发针对鲍曼不动杆菌的嵌合疫苗。

Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii.

机构信息

Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer, 305817, India.

出版信息

Sci Rep. 2018 Jun 13;8(1):9044. doi: 10.1038/s41598-018-26689-7.

Abstract

The emergence of drug-resistant Acinetobacter baumannii is the global health problem associated with high mortality and morbidity. Therefore it is high time to find a suitable therapeutics for this pathogen. In the present study, subtractive proteomics along with reverse vaccinology approaches were used to predict suitable therapeutics against A. baumannii. Using subtractive proteomics, we have identified promiscuous antigenic membrane proteins that contain the virulence factors, resistance factors and essentiality factor for this pathogenic bacteria. Selected promiscuous targeted membrane proteins were used for the design of chimeric-subunit vaccine with the help of reverse vaccinology. Available best tools and servers were used for the identification of MHC class I, II and B cell epitopes. All selected epitopes were further shortlisted computationally to know their immunogenicity, antigenicity, allergenicity, conservancy and toxicity potentials. Immunogenic predicted promiscuous peptides used for the development of chimeric subunit vaccine with immune-modulating adjuvants, linkers, and PADRE (Pan HLA-DR epitopes) amino acid sequence. Designed vaccine construct V4 also interact with the MHC, and TLR4/MD2 complex as confirm by docking and molecular dynamics simulation studies. Therefore designed vaccine construct V4 can be developed to control the host-pathogen interaction or infection caused by A. baumannii.

摘要

耐多药鲍曼不动杆菌的出现是一个全球性的健康问题,与高死亡率和高发病率有关。因此,现在是时候为这种病原体找到合适的治疗方法了。在本研究中,采用消减蛋白质组学和反向疫苗学方法来预测针对鲍曼不动杆菌的合适治疗方法。通过消减蛋白质组学,我们已经鉴定了具有混杂抗原性的膜蛋白,这些蛋白包含了这种致病菌的毒力因子、耐药因子和必需因子。选择的混杂靶向膜蛋白用于设计嵌合亚单位疫苗,这得益于反向疫苗学。使用了现有的最佳工具和服务器来鉴定 MHC Ⅰ类、Ⅱ类和 B 细胞表位。所有选定的表位都进行了计算,以了解它们的免疫原性、抗原性、变应原性、保守性和毒性潜力。预测具有免疫原性的混杂肽用于开发嵌合亚单位疫苗,使用免疫调节佐剂、连接子和 PADRE(泛 HLA-DR 表位)氨基酸序列。设计的疫苗构建体 V4 还与 MHC 和 TLR4/MD2 复合物相互作用,这通过对接和分子动力学模拟研究得到了证实。因此,设计的疫苗构建体 V4 可用于控制宿主-病原体相互作用或由鲍曼不动杆菌引起的感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6414/5997985/347bc39354ec/41598_2018_26689_Fig1_HTML.jpg

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