沙门氏菌宽谱噬菌体对不同宿主菌侵染效力差异的分子机理研究

批准号:
32001834
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
李梦哲
依托单位:
学科分类:
食品科学研究的新方法
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
李梦哲
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中文摘要
宽谱噬菌体作为新型抗菌剂可有效防控沙门氏菌及其食源性疾病。但宽谱噬菌体仅对部分宿主菌具有强效侵染效力,无法满足在宽裂解谱内充分清除细菌的应用要求。因此,亟需探明宽谱噬菌体对不同宿主菌侵染效力差异的产生机制。结合前期研究基础,申请人推测参与吸附过程的结构蛋白构象会影响其与宿主菌上靶分子结合力而使噬菌体侵染效力产生差异。本项目拟以沙门氏菌宽谱噬菌体STP4-a为研究对象,通过进化性增殖方式获取侵染效力增强的噬菌体进化株;利用比较基因组学明确引起侵染效力增强的关键结构蛋白,并确定其宿主菌上的靶分子;采用同源建模等技术预测噬菌体关键结构蛋白及其与靶分子结合的空间构象变化,并通过表面等离子共振技术表征两者之间结合力变化,从而阐明噬菌体进化株侵染效力变化的根本原因,依此揭示宽谱噬菌体对不同宿主菌侵染效力差异的机理,为全面增强宽谱噬菌体的侵染效力、高效防控沙门氏菌及其疾病提供重要的理论依据和技术支撑。
英文摘要
As a new antibacterial agent, the broad-host-range bacteriophage (phage) can effectively prevent and control Salmonella and its foodborne diseases. However, the broad-host-range phage exhibits strong infectivity only on part of its hosts, which cannot meet the requirement of eliminating all bacteria within the broad host range. Therefore, it is imperative to explore how the broad-host-range phage varies its infectivity on different hosts. Based on the previous research, we hypothesize that the conformation of structural proteins involved in the adsorption process will affect the binding affinity with the target molecule of its hosts, and then enable the phage to vary its infectivity on different hosts. In this study, we first choose the broad-host-range Salmonella phage STP4-a as the research target and use different Salmonella hosts to evolve it for preparing evolved phage STP4-a with enhanced infectivity. After that, by comparing the variation of the genome sequences of phage STP4-a and its evolved ones, we can obtain the mutated structural proteins which are key to influence phage infectivity, and then we can determine their corresponding target molecules on the Salmonella hosts. Finally, via homology modeling and other technologies, the variations of key structural proteins and their binding with target molecules are analyzed from the perspective of spatial conformation; and then their binding affinity can be determined and verified using the surface plasmon resonance technology, which can be used to explain the enhancement of evolved phage infectivity. From the above analysis, the molecular mechanism of broad-host-range phages varying its infectivity on different hosts can be obtained. This research will provide a fundamental theoretical basis and technical support for thoroughly enhancing the infectivity of broad-host-range phages as well as efficiently preventing and controlling Salmonella and foodborne diseases caused by Salmonella.
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DOI:10.3389/fmicb.2023.1230775
发表时间:2023
期刊:Frontiers in microbiology
影响因子:5.2
作者:
通讯作者:
DOI:10.3390/ijms242115594
发表时间:2023-10-26
期刊:International journal of molecular sciences
影响因子:5.6
作者:
通讯作者:
DOI:10.1016/j.foodcont.2021.108178
发表时间:2021-04
期刊:Food Control
影响因子:6
作者:Mengzhe Li;Z. Luan;Yongxiang Liu;Chen Yang;Yanling Wang;Cuiping Ma;Chao Shi
通讯作者:Mengzhe Li;Z. Luan;Yongxiang Liu;Chen Yang;Yanling Wang;Cuiping Ma;Chao Shi
Complete genome sequence of the extreme-pH-resistant Salmonella bacteriophage αα of the family Microviridae
微病毒科耐极端 pH 值沙门氏菌噬菌体 α α 的完整基因组序列
DOI:10.1007/s00705-020-04880-4
发表时间:2020-11-22
期刊:ARCHIVES OF VIROLOGY
影响因子:2.7
作者:Li, Mengzhe;Lin, Hong;Wang, Jingxue
通讯作者:Wang, Jingxue
国内基金
海外基金
