A pan-genomic analysis based multi-epitope vaccine development by targeting Stenotrophomonas maltophilia using reverse vaccinology method: an in-silico approach.

In silico pharmacology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.1007/s40203-024-00271-8
Md Hasan Jafre Shovon, Md Imtiaz, Partha Biswas, Md Mohaimenul Islam Tareq, Md Nazmul Hasan Zilani, Md Nazmul Hasan
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Abstract

Antibiotic resistance in bacteria leads to high mortality rates and healthcare costs, a significant concern for public health. A colonizer of the human respiratory system, Stenotrophomonas maltophilia is frequently associated with hospital-acquired infections in individuals with cystic fibrosis, cancer, and other chronic illnesses. The importance of this study is underscored by its capacity to meet the critical demand for effective preventive strategies against this pathogen, particularly among susceptible groups of cystic fibrosis and those undergoing cancer treatment. In this study, we engineered a multi-epitope vaccine targeting S. maltophilia through genomic analysis, reverse vaccination strategies, and immunoinformatic techniques by examining a total of 81 complete genomes of S. maltophilia strains. Our investigation revealed 1945 core protein-coding genes alongside their corresponding proteomic sequences, with 191 of these genes predicted to exhibit virulence characteristics. Out of the filtered proteins, three best antigenic proteins were selected for epitope prediction while seven epitopes each from CTL, HTL, and B cell were chosen for vaccine development. The vaccine was refined and validated, showing highly antigenic and desirable physicochemical features. Molecular docking assessments revealed stable binding with TLR-4. Molecular dynamic simulation demonstrated stable dynamics with minor alterations. The originality of this investigation is rooted in the thorough techniques aimed at designing a vaccine that directly targets S. maltophilia, a microorganism of considerable clinical relevance that currently lacks an available vaccine. This study not only responds to a pressing public health crisis but also lays the groundwork for subsequent research endeavors focused on the prevention of S. maltophilia outbreaks. Further evidence from studies in mice models is needed to confirm immune protection against S. maltophilia.

利用反向疫苗学方法,针对嗜麦芽僵单胞菌开发基于泛基因组分析的多表位疫苗:一种内科学方法。
细菌的抗生素耐药性会导致很高的死亡率和医疗成本,是公共卫生的一个重大问题。嗜麦芽气单胞菌是人类呼吸系统的定植菌,经常与囊性纤维化患者、癌症患者和其他慢性病患者在医院获得性感染有关。这项研究的重要性在于它能够满足对这种病原体的有效预防策略的迫切需求,特别是在囊性纤维化易感人群和接受癌症治疗的人群中。在这项研究中,我们通过基因组分析、反向接种策略和免疫形式学技术,共检测了 81 株嗜麦芽糖酵母菌的完整基因组,从而设计出了针对嗜麦芽糖酵母菌的多表位疫苗。我们的研究发现了 1945 个核心蛋白编码基因及其相应的蛋白质组序列,其中 191 个基因被预测具有毒力特征。在筛选出的蛋白质中,我们选择了三个最佳抗原蛋白进行表位预测,并从 CTL、HTL 和 B 细胞中各选择了七个表位进行疫苗开发。疫苗经过改进和验证,显示出高抗原性和理想的理化特征。分子对接评估显示与 TLR-4 的结合稳定。分子动力学模拟显示了稳定的动态变化。这项研究的独创性在于采用了全面的技术,旨在设计一种直接针对嗜麦芽糖酵母菌的疫苗,这种微生物具有相当大的临床意义,但目前还没有可用的疫苗。这项研究不仅对紧迫的公共卫生危机做出了回应,而且还为后续以预防嗜麦芽糖酵母菌爆发为重点的研究工作奠定了基础。还需要小鼠模型研究的进一步证据来证实对嗜麦芽糖酵母菌的免疫保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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