PDF(Pubmed)
Abstract：
Escherichia fergusonii a gram-negative rod-shaped bacterium in the Enterobacteriaceae family, infect humans, causing serious illnesses such as urinary tract infection, cystitis, biliary tract infection, pneumonia, meningitis, hemolytic uremic syndrome, and death. Initially treatable with penicillin, antibiotic misuse led to evolving resistance, including resistance to colistin, a last-resort drug. With no licensed vaccine, the study aimed to design a multi-epitope vaccine against E. fergusonii. The study started with the retrieval of the complete proteome of all known strains and proceeded to filter the surface exposed virulent proteins. Seventeen virulent proteins (4 extracellular, 4 outer membranes, 9 periplasmic) with desirable physicochemical properties were identified from the complete proteome of known strains. Further, these proteins were processed for B-cell and T-cell epitope mapping. Obtained epitopes were evaluated for antigenicity, allergenicity, solubility, MHC-binding, and toxicity and the filtered epitopes were fused by specific linkers and an adjuvant into a vaccine construct. Structure of the vaccine candidate was predicted and refined resulting in 78.1% amino acids in allowed regions and VERIFY3D score of 81%. Vaccine construct was docked with TLR-4, MHC-I, and MHC-II, showing binding energies of -1040.8 kcal/mol, -871.4 kcal/mol, and -1154.6 kcal/mol and maximum interactions. Further, molecular dynamic simulation of the docked complexes was carried out resulting in a significant stable nature of the docked complexes (high B-factor and deformability values, lower Eigen and high variance values) in terms of intermolecular binding conformation and interactions. The vaccine was also reported to stimulate a variety of immunological pathways after administration. In short, the designed vaccine revealed promising predictions about its immune protective potential against E. fergusonii infections however experimental validation is needed to validate the results.
摘要：
肠杆菌科中的一种革兰氏阴性杆状细菌，感染人类,引起严重的疾病，如尿路感染，膀胱炎,胆道感染,肺炎,脑膜炎,溶血性尿毒综合征,和死亡。最初可以用青霉素治疗，抗生素的滥用导致了耐药性的演变，包括对粘菌素的抗性，最后的药物.没有许可疫苗，该研究旨在设计一种针对E.Fergusonii的多表位疫苗。该研究从检索所有已知菌株的完整蛋白质组开始，并开始过滤表面暴露的有毒蛋白质。17种毒力蛋白（4种细胞外，4个外膜，9周质）从已知菌株的完整蛋白质组中鉴定出具有理想的物理化学特性。Further,这些蛋白质被加工用于B细胞和T细胞表位作图。评估获得的表位的抗原性，变应原性,溶解度，MHC结合，和毒性和过滤的表位通过特异性接头和佐剂融合到疫苗构建体中。预测并精制疫苗候选物的结构,导致允许区域中78.1%的氨基酸和81%的VERIFY3D评分。疫苗构建体与TLR-4，MHC-I，和MHC-II，显示结合能为-1040.8kcal/mol，-871.4千卡/摩尔，和-1154.6kcal/mol和最大相互作用。Further,对接配合物的分子动力学模拟进行，导致对接配合物的显着稳定性质（高B因子和变形性值，在分子间结合构象和相互作用方面，Eigen值较低且方差值较高）。还报道了该疫苗在给药后刺激多种免疫途径。总之,设计的疫苗揭示了其对E.Fergusonii感染的免疫保护潜力的有希望的预测，但需要实验验证来验证结果。
