乳酸菌抗菌肽拮抗食源性大肠杆菌感染机制的研究

It is necessary to develop new methods to alleviate foodborne diseases caused by pathogenic bacterium and replace antibiotic therapy. Based on the previous studies on the antagonism of Lactobacillus plantarum against food-borne pathogens, this project intends to select the probiotic Lactobacillus plantarum with excellent antibacterial characteristics as the research object, and the antibacterial phenotype and biological characteristics of its antimicrobial peptide was studied. In order to analyze the mechanism of antimicrobial peptides inhibiting Escherichia coli infection in vivo, the regulation of antimicrobial peptide on host intestinal flora, intestinal inflammation and barrier impairment were systematically evaluated in an animal model of E. coli infection, by combining with the correlation analysis of physiological and biochemical changes of the host, inflammatory cytokines and flora differences. The implementation and completion of this project can provide a theoretical basis for the development and application of innovative drugs for the prevention and treatment of foodborne diseases.

开发缓解致病菌引起的食源性疾病的新方法，替代抗生素疗法是目前亟待解决的问题。本项目以植物乳杆菌拮抗食源性致病菌的前期研究为基础，拟选取具有优良抑菌特性的益生植物乳杆菌为研究对象，考察其抗菌肽抑菌表型特征和生物学特性，在此基础上通过大肠杆菌感染动物模型系统评价抗菌肽对宿主肠道菌群、肠道炎症和屏障功能损伤的调控作用，结合宿主生理生化、炎症因子和菌群差异性变化的关联分析，解析抗菌肽在体内抑制大肠杆菌感染机制机理。该项目的实施和完成，可为预防和治疗食源性疾病的创新性药物的开发和应用提供理论基础。

开发安全、稳定、有效的天然抗菌剂来减少甚至取代抗生素的使用是目前亟待解决的问题。植物乳植杆菌及其抗菌肽可以控制潜在病原体和机会性物种的生长，从而在确保肠道生态系统动态平衡的复杂关系网络中发挥相关作用，并有益于宿主健康。本项目建立了基于基于图神经网络的乳酸菌抗菌肽预测模型，搭建了乳酸菌抗菌肽预测公共数据库，依托内蒙古农业大学乳酸菌菌种资源库，从264株植物乳植杆菌中筛选获得具有优良抑菌特性的益生植物乳植杆菌IMAU80122，系统考察了其抑菌物质的生物学特性，利用全基因组测序、现代组学技术挖掘其所产抗菌肽，定位了抗菌肽编码基因plnEF、plnA、plnN等。通过动物模型实验发现其对炎症性肠病具有积极的改善作用，可有效改善小鼠腹泻，并通过增加Th2的表达以及抑制Th1和Th17的表达来缓解小鼠炎症性肠病的影响。本项目的完成可为具有抑菌特性乳酸菌的筛选，缓解炎症性肠病的创新性药物的开发奠定基础。通过三年的实施，本项目形成SCI收录论文2篇；培养硕士研究生2名；授权发明专利2项。