革兰氏阴性病原菌外膜囊泡的生物学作用与机制研究进展  

Research Progress on Biological Roles and Mechanisms of Outer Membrane Vesicles Derived From Gram-negative Pathogenic Bacteria

作　　者：李春玲 柯海意 徐民生 卞志标 张昆丽 李艳 翟少伦 LI Chunling;KE Haiyi;XU Minsheng;BIAN Zhibiao;ZHANG Kunli;LI Yan;ZHAI Shaolun(Institute of Animal Health,Guangdong Academy of Agricultural Sciences/Guangdong Key Laboratory of Livestock Disease Prevention/Guangdong Open Laboratory of Veterinary Public Health/Guangdong Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Techniques,Ministry of Agriculture and Rural Affairs,Guangzhou 510640,China;Guangdong Gaozhou Agricultural School,Maoming 525000,China)

机构地区：[1]广东省农业科学院动物卫生研究所/广东省畜禽疫病防治重点实验室/广东省兽医公共卫生开放实验室/农业农村部兽用药物与兽医生物技术广东科学观测实验站,广东广州510640 [2]广东省高州农业学校,广东茂名525000

出　　处：《广东农业科学》2023年第7期1-10,共10页Guangdong Agricultural Sciences

基　　金：国家自然科学基金面上项目(31772776);广东省现代农业产业技术体系创新团队项目(2019KJ119);广东省自然科学基金(2023A1515012206)。

摘　　要：外膜囊泡(Outer membrane vesicles,OMV)是兰氏阴性菌分泌的纳米样颗粒。OMV呈球状双层膜结构,直径为20~250 nm大小。其主要由细菌的外膜成分构成,其中病原菌分泌的OMV包括与致病相关的多种成分,如非蛋白抗原脂多糖、脂质、蛋白质粘附素、侵袭素、毒素等致病因子。病原菌OMV还含有细菌的DNA、RNA、sRNA和质粒等核酸,是革兰氏阴性菌的一种新型分泌系统,与致病性、耐药基因的存储和传播、细菌间及细菌-宿主间通信串扰等一系列功能紧密相关。病原菌OMV的分泌与应激反应有关。OMV作为毒力因子、耐药基因或质粒、抗原分子等生物活性物质的载体递送至宿主细胞,直接导致疫病的发生或加剧病情。在作用机制方面,OMV通过动力依赖性内吞将毒素转运至宿主细胞、介导耐药基因水平转移、通过增加分泌量减少噬菌体入侵病原菌,或保护来源菌、周围细菌免受膜活性物质侵害、影响,以及诱导细菌感染部位甚至远部组织免疫相关细胞的免疫反应、激活炎症反应通路、介导宿主细胞死亡及代谢重构等。鉴于OMV在细菌致病、耐药性产生、宿主生理屏障(肠黏膜屏障、肠血管屏障、血脑屏障)破坏及生态位失衡、免疫功能异常等方面发挥的多种生物学功能,深入了解其相关生物学作用和潜在的分子机制,对探索人和动物细菌病的致病机制、耐药机理、开展药物靶向递送系统研发及新型疫苗创制等防控新策略具有重要意义。重点对OMV在革兰氏阴性病原菌致病过程中的作用及分子机制相关研究进展进行综述,并对其应用进行展望。Outer membrane vesicles(OMV)are nanoplike particles secreted by Gram-negative(G-)bacteria.OMV are spherical,bilayer membrane-like structures,mostly 20 to 250 nm in diameter.They are mainly composed of the outer membrane components of bacteria.OMV secreted by pathogens include various components associated with pathogenesis,such as non-protein antigenic lipopolysaccharides,lipids,protein adhesins,invasins,toxins and other pathogenic factors.Pathogenic OMV also contain bacterial DNA,RNA,sRNA and plasmid nucleic acids from bacteria.OMV have been termed a new secretion system of Gram-negative bacteria,which is closely related to a series of functions such as pathogenicity,storage and transmission of drug resistance genes,interbacterial and bacteria-host communication crosstalk.Secretion of pathogenic OMV is associated with the stress response.OMV are considered carriers of virulence factors,drug resistance genes,plasmids,antigen molecules and other bioactive substances and delivered to the host cells.They can lead to the occurrence of epidemics directly or exacerbate the disease.In terms of mechanism,OMV transport toxins to host cells through dynamic-dependent endocytosis,mediate horizontal transfer of drug resistance genes,reduce phage invasion by increasing secretion or protect pathogens of source bacteria or surrounding bacteria from membrane active substances,affect and induce immune responses of cells related to bacterial infection sites or even distant tissues and so on.It can further activate inflammatory response pathways,mediate host cell death and metabolic remodeling.In virtue of the series of biological functions in bacterial pathogenesis,drug resistance,the host physiological barrier(intestinal mucosa barrier,intestinal vessel barrier and blood-brain barrier)damage,niche imbalance of OMV and so forth,it’s of great significance to understand their related biological roles and potential molecular mechanism for developing newly prevention and control strategies.In this review,we focus on the role of OMV a

关 键 词：革兰氏阴性病原菌 外膜囊泡 致病性 生物学作用 分泌系统 

分 类 号：S855.1[农业科学—临床兽医学]