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Exploiting the power of OMICS approaches to produce E. coli O157 vaccines

机译:利用OMICS方法生产大肠杆菌O157疫苗的能力

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摘要

Enterohemorrhagic Escherichia coli (EHEC) strains are well-documented human pathogens and causative agents of diarrheal episodes and hemorrhagic colitis. The serotype O157:H7 is highly virulent and responsible for both outbreaks and sporadic cases of diarrhea. Because antibiotic treatment is contraindicated against this pathogen, development of a human vaccine could be an effective intervention in public health. In our recent Infection and Immunity paper, we applied integrated approaches of in silico genome wide search combined with bioinformatics tools to identify and test O157 vaccine candidates for their protective effect on a murine model of gastrointestinal infection. Using genomic/immunoinformatic approaches that are further described here, we categorized vaccine candidates as high, medium, and low priorities, and demonstrate that some high priority candidates were able to significantly induce Th2 cytokines and reduce EHEC colonization. Using the STRING database, we have recently evaluated the vaccine candidates and predict functional protein interactions, determining whether correlations exist for the development of a multi-subunit vaccine, targeting different pathways against EHEC O157:H7. The overall approach is designed to screen potential vaccine candidates against EHEC; however, the methodology can be quickly applied to many other intestinal pathogens.
机译:肠出血性大肠杆菌(EHEC)菌株是有据可查的人类病原体,是腹泻发作和出血性结肠炎的病原体。血清型O157:H7具有高毒力,可引起暴发和偶尔的腹泻。由于禁止使用抗生素治疗这种病原体,因此开发人类疫苗可能是对公共卫生的有效干预措施。在我们最近的《感染与免疫》一文中,我们应用了计算机模拟全基因组搜索与生物信息学工具相结合的集成方法,以识别和测试O157候选疫苗对小鼠胃肠道感染模型的保护作用。使用在这里进一步描述的基因组/免疫信息学方法,我们将候选疫苗分为高优先级,中优先级和低优先级,并证明了一些高优先级候选物能够显着诱导Th2细胞因子并减少EHEC定植。使用STRING数据库,我们最近评估了候选疫苗并预测了功能性蛋白质相互作用,确定了针对针对EHEC O157:H7的不同途径的多亚基疫苗的开发是否存在相关性。总体方法旨在筛选针对EHEC的潜在候选疫苗;但是,该方法可以快速应用于许多其他肠道病原体。

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