迟钝爱德华菌抗血浆杀菌作用的组学研究

On the basis of the previous work, systems biology approach will be used to investigate Edwardsiealla tarda mechanism in resistance to plasma. First, the E. tarda cells cultured in plasma are investigated at three levels of transcripome, proteomics and metabolome, and the interaction and its network between soluble serum proteins and outer membrane proteins are constructed. Then, the relashionship between differential genes, proteomics and metabolites is revealed and primary systems model is constructed using bioinformatics. Third, the primary model is functionally validated through gene deletion and over-expression, enzyme activity and compound addition. Fourth, the molecular systems model of E. tarda resistance to plasma is developed based on the modification of the primary model through these functional assays. At last, whether crucial upregulated proteins selected from the molecular systems model are efficient protective immunogens is investigated for development of a new approach to identify highly protective vaccine candidates from the key proteins in the systems model. These systematic investigation may clarify the molecular mechanism of E. tarda to resist plasma, and provide information on how to inhibit the bacterial infection stage of blood.

在前期研究的基础上，开展迟缓爱德华氏菌（E. tarda）抗血浆杀菌作用的组学研究。首先，从转录组学、蛋白质组学和代谢组学等三个组学水平对血浆作用后的E. tarda进行系统研究。同时探讨外膜蛋白与血浆蛋白相互作用及其网络。然后，采用生物信息学研究所鉴定的全部基因、蛋白质和小分子及其组分间的相互关系，揭示E. tarda抗血浆作用的初步组学机制。接着，采用基因缺失、高表达和酶活性测定以及添加重要小分子物质等功能试验，对上述初步组学机制进行验证，并进行反复修正，阐明E. tarda抗血浆杀菌作用的组学应答规律。此外，依据组学应答规律，对相互作用网络中上调表达的关键蛋白进行免疫攻毒保护作用的评价，试图建立一条基于组学机制从重要功能蛋白中发现高效保护原的新途径。通过这些系统研究，以阐明E. tarda抗血浆杀菌作用的分子机制，并为阻断该感染环节奠定理论和应用基础。