Department of Pharmaceuticals and Industrial Biotechnology, Sylhet Agricultural University, Sylhet, Bangladesh.
Department of Microbial Biotechnology, Sylhet Agricultural University, Sylhet, Bangladesh.
PLoS One. 2020 Aug 19;15(8):e0237181. doi: 10.1371/journal.pone.0237181. eCollection 2020.
Multidrug-resistant Vibrio parahaemolyticus has become a significant public health concern. The development of effective drugs and vaccines against Vibrio parahaemolyticus is the current research priority. Thus, we aimed to find out effective drug and vaccine targets using a comprehensive genome-based analysis. A total of 4822 proteins were screened from V. parahaemolyticus proteome. Among 16 novel cytoplasmic proteins, 'VIBPA Type II secretion system protein L' and 'VIBPA Putative fimbrial protein Z' were subjected to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, 'Sensor histidine protein kinase UhpB' and 'Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T-cell and B-cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking analysis to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules- results suggested that the V1 is superior. Besides, the binding affinity of human TLR-1/2 heterodimer and construct V1 could be biologically significant in the development of the vaccine repertoire. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied using model animals to combat V. parahaemolyticus associated infections.
耐多药副溶血性弧菌已成为一个重大的公共卫生关注点。开发针对副溶血性弧菌的有效药物和疫苗是当前的研究重点。因此，我们旨在通过全面的基于基因组的分析来寻找有效的药物和疫苗靶点。从副溶血性弧菌的蛋白质组中筛选出 4822 种蛋白质。在 16 种新型细胞质蛋白中，“VIBPA 型 II 型分泌系统蛋白 L”和“VIBPA 假定纤毛蛋白 Z”与 350 个人类代谢物进行分子对接，结果表明依利格鲁司他、辛伐他汀和羟钴胺素是考虑到自由结合能的最佳药物分子。相反，“传感器组氨酸蛋白激酶 UhpB”和“25 种新型膜蛋白的鞭毛钩相关蛋白”进行 T 细胞和 B 细胞表位预测、抗原性测试、跨膜拓扑筛选、变应原性和毒性评估、人群覆盖率分析和分子对接分析，以产生最具免疫原性的表位。三种亚单位疫苗通过与合适的佐剂、PADRE 序列和接头相结合的高度抗原性表位构建。设计的疫苗构建体（V1、V2、V3）通过其物理化学性质和与 MHC 分子的分子对接进行分析-结果表明 V1 更优越。此外，人 TLR-1/2 异二聚体与构建体 V1 的结合亲和力在疫苗库的开发中可能具有生物学意义。疫苗-受体复合物表现出最小水平的变形性，这也加强了我们的预测。设计构建体的优化密码子被克隆到大肠杆菌 K12 菌株的 pET28a(+)载体中。然而，预测的药物分子和疫苗构建体可以进一步在模型动物中进行研究，以对抗副溶血性弧菌相关感染。
