植物乳杆菌CCFM679拮抗单核细胞增生李斯特菌感染的作用机制研究

Listeria monocytogenes is facultative anaerobic gram-positive food-borne pathogens, having the capacity of cell proliferation, and defined as one of the four major foodborne pathogens by the World Health Organization. Currently, Listeria monocytogenes infection is mainly treated with antibiotics, but with the antibiotics being widely used in the treatment and prevention of Listeria monocytogenes, Listeria monocytogenes led to the emergence of drug resistance. Microecological biologic therapies, including lactic acid bacteria, become an effective alternative pathway to prevent and treat intestinal pathogen infection. Based on Lactobacillus plantarum CCFM 679 with antagonistic activities against Listeria monocytogenes that has been screened out previously, both the antagonistic activities against Listeria monocytogenes to adhere and invade cell by Lactobacillus plantarum, and its metabolites and the role to intervene the cause intestinal damage in the host by Listeria monocytogenes were researched, The changes of intestinal microflora are analyzed, and the relevance of intestinal flora changes and Listeria monocytogenes infection is also clarified, as well as the intervention mechanism of Lactobacillus plantarum on intestinal infection by Listeria monocytogenes is illuminated, in order to supply a theoretical basis for the development and utilization of functional lactic acid bacteria.

单核细胞增生李斯特菌是能够细胞内增殖的兼性厌氧革兰氏阳性食源性致病菌，被世界卫生组织定义为四大食源性病原菌之一。目前对单增李斯特菌感染主要采用以抗生素为主的治疗策略，但是随着抗生素在治疗和预防方面的广泛使用，导致单增李斯特菌出现耐药性。利用包括乳酸菌在内的微生态生物疗法预防和治疗肠道致病菌感染成为一种有效的替代途径。本课题在前期获得的具有拮抗单增李斯特菌的植物乳杆菌CCFM679的基础上，利用细胞模型和动物模型，研究该菌及其代谢产物拮抗单增李斯特菌黏附、侵入细胞以及干预单增李斯特菌导致宿主肠道损伤中所发挥的作用，解析此菌干预单增李斯特菌感染后肠道菌群结构的变化，揭示肠道菌群变化与单增李斯特菌感染之间的关联性，阐明植物乳杆菌拮抗单增李斯特菌感染的作用机理，为功能性乳酸菌的开发和利用奠定理论依据。

单核细胞增生李斯特菌是能够细胞内增殖的兼性厌氧革兰氏阳性食源性致病菌，被世界卫.生组织定义为主要的食源性病原菌之一。目前对单增李斯特菌感染主要采用以抗生素为主的治疗策略，但是随着抗生素在治疗和预防方面的广泛使用，导致单增李斯特菌出现耐药性。利用包括乳酸菌在内的微生态生物疗法预防和治疗肠道致病菌感染成为一种有效的替代途径。利用HT-29细胞模型，研究了植物乳杆菌干预单增李斯特菌黏附、侵入细胞的因素，实验结果表明植物乳杆菌主要通过空间位阻和占位效应干预单增李斯特菌黏附、侵入HT-29细胞。构建了单增李斯特菌感染C57小鼠动物模型，通过动物肠道组织切片分析、细胞因子、炎症因子、基因转录水平等指标，研究了植物乳杆菌在拮抗单增李斯特菌引发宿主肠道损伤中所发挥的作用。同时，利用高通量测序方法，阐明了植物乳杆菌干预单增李斯特菌感染小鼠肠道菌群结构的变化，分析了肠道菌群变化与单增李斯特菌感染之间的关联性。本项目的研究有助于避免单增李斯特菌污染，保护人类食品安全，同时为功能性乳酸菌的开发和应用提供了理论依据。.