肠道益生菌天然分离株H24对大肠杆菌O157：H7感染的抑制作用研究
发布时间：2019-06-19 18:51
【摘要】：肠出血性大肠杆菌O157∶H7作为新发传染病病原菌可以导致出血性肠炎(hemorrhagic colitis，HC)和肾溶血性尿毒综合症(hemolytic uremic syndrome，HUS)，严重危害人类的身体健康。抗生素一般不能用于临床治疗大肠杆菌O157∶H7的感染性疾病。原因在于：传统的治疗过程中所使用的抗生素是基于以与细菌细胞的生长分裂有密切关系的系统为靶位点所分离得到的化合物。因为该类化合物的筛选原则是杀死或抑制细菌细胞的生长，因此会造成细菌细胞的SOS系统激活，进而导致O157∶H7基因组中溶原型噬菌体933v和933w分别编码的志贺毒素Stx1和Stx2的短期大量表达，从而加速宿主的死亡。所以，筛选不诱导志贺毒素表达的药物和／或益生菌，以预防和控制大肠杆菌O157∶H7等病原菌感染引发的疾病，在理论和临床疾病预防控制上都有重要意义。本文拟研究利用芽孢菌类益生菌控制大肠杆菌O157∶H7感染的可行性。 细菌细胞间通讯系统，即群体感应(quorum sensing，QS)系统在协调病原菌在感染宿主的过程中各项生理活动中发挥着举足轻重的作用，该系统通过自身产生一类称为自诱导物质(autoinducer，AI)的化学信号分子协调细菌整个群体的生理活动，许多病原菌的毒素释放就受QS系统的调控。因此，以大肠杆菌O157∶H7等病原菌的QS系统为靶位点所筛选得到的抗菌药物(antibacterials)，有可能不直接杀死细菌，而仅仅只是阻断或干扰群体中个体之间的交流、进而阻止它们释放毒素，成为目前国际上药物筛选的最新空间。 肠道益生菌是治疗O157∶H7等肠道病原微生物感染的另一途径，，比起抗生素有其优势的方面，其中就包括不会造成抗药性的产生。而且本文所研究的H24菌株是对鸡、猪、牛等动物腹泻具有普遍的预防、治疗或辅助治疗作用的益生菌，该菌株经本文鉴定为芽孢杆菌属的解淀粉芽孢杆菌(Bacillus amyloliquefaciens)。本研究以群体感应理论为指导，提取H24的天然发酵产物，分别以体外(in vitro)、体内(in vivo)方式研究该天然菌株对肠出血性大肠杆菌O157∶H7菌Sakai株的抑制作用。 体外实验部分包括H24的天然发酵产物对Sakai菌株生物膜形成的抑制作用的研究以及对Sakai菌株志贺毒素表达抑制作用的研究。其中O157生物膜的形成与志贺毒素的表达都间接受控于该病原菌的QS系统，并且这两项指标也是该菌致病力的重要组成部分。
[Abstract]:Enterohemorrhagic Escherichia coli (O157:H7), as a pathogen of new infectious diseases, can lead to hemorrhagic enteritis (hemorrhagic colitis,HC) and renal hemolytic uremic syndrome (hemolytic uremic syndrome,HUS), which seriously endangers human health. Antibiotics can not be used in clinical treatment of infectious diseases of Escherichia coli O157:H7. The reason is that the antibiotics used in the traditional treatment are based on the compounds isolated from the system which is closely related to the growth and division of bacterial cells. Because the screening principle of these compounds is to kill or inhibit the growth of bacterial cells, it will cause the activation of SOS system of bacterial cells, which will lead to the short-term expression of Shiga toxin Stx1 and Stx2 encoded by lytic bacteriophages 933v and 933w in O157:H7 genome, thus accelerating the death of hosts. Therefore, screening drugs and / or probiotics that do not induce Shiga toxin expression in order to prevent and control diseases caused by pathogenic bacteria such as Escherichia coli O157:H7 is of great significance in both theoretical and clinical disease prevention and control. In this paper, the feasibility of using Bacillus probiotics to control Escherichia coli O157:H7 infection was studied. Bacterial intercellular communication system, quartile induction (quorum sensing,QS) system, plays an important role in coordinating the physiological activities of pathogenic bacteria in the process of infecting the host. The system coordinates the physiological activities of the whole bacterial population by producing a class of chemical signal molecules called self-inducing substance (autoinducer,AI). The toxin release of many pathogens is regulated by QS system. Therefore, the antibacterial drug (antibacterials), screened by the QS system of E. coli O157:H7 and other pathogens may not kill bacteria directly, but only block or interfere with the communication between individuals in the population, and then prevent them from releasing toxins, which has become the latest space for drug screening in the world at present. Intestinal probiotics is another way to treat intestinal pathogenic microbial infections such as O157:H7, which has its advantages over antibiotics, including the lack of drug resistance. Moreover, the H24 strain studied in this paper is a probiotics which has universal preventive, therapeutic or auxiliary therapeutic effect on diarrhea in chickens, pigs, cattle and other animals. The strain has been identified as Bacillus amylopectin (Bacillus amyloliquefaciens). In this paper. In this study, the natural fermentation products of H24 were extracted under the guidance of quartile induction theory, and the inhibitory effect of the natural strain on enterohemorrhagic Escherichia coli O157:H7 strain Sakai was studied by (in vivo) in vitro (in vitro),. In vitro experiments included the inhibitory effect of H24 natural fermentation products on biofilm formation of Sakai strain and the inhibitory effect on the expression of Shiga toxin of Sakai strain. The formation of O157 biofilm and the expression of Shiga toxin are indirectly controlled by the QS system of the pathogen, and these two indexes are also an important part of the pathogenicity of the pathogen.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R371
本文编号：2502567
[Abstract]:Enterohemorrhagic Escherichia coli (O157:H7), as a pathogen of new infectious diseases, can lead to hemorrhagic enteritis (hemorrhagic colitis,HC) and renal hemolytic uremic syndrome (hemolytic uremic syndrome,HUS), which seriously endangers human health. Antibiotics can not be used in clinical treatment of infectious diseases of Escherichia coli O157:H7. The reason is that the antibiotics used in the traditional treatment are based on the compounds isolated from the system which is closely related to the growth and division of bacterial cells. Because the screening principle of these compounds is to kill or inhibit the growth of bacterial cells, it will cause the activation of SOS system of bacterial cells, which will lead to the short-term expression of Shiga toxin Stx1 and Stx2 encoded by lytic bacteriophages 933v and 933w in O157:H7 genome, thus accelerating the death of hosts. Therefore, screening drugs and / or probiotics that do not induce Shiga toxin expression in order to prevent and control diseases caused by pathogenic bacteria such as Escherichia coli O157:H7 is of great significance in both theoretical and clinical disease prevention and control. In this paper, the feasibility of using Bacillus probiotics to control Escherichia coli O157:H7 infection was studied. Bacterial intercellular communication system, quartile induction (quorum sensing,QS) system, plays an important role in coordinating the physiological activities of pathogenic bacteria in the process of infecting the host. The system coordinates the physiological activities of the whole bacterial population by producing a class of chemical signal molecules called self-inducing substance (autoinducer,AI). The toxin release of many pathogens is regulated by QS system. Therefore, the antibacterial drug (antibacterials), screened by the QS system of E. coli O157:H7 and other pathogens may not kill bacteria directly, but only block or interfere with the communication between individuals in the population, and then prevent them from releasing toxins, which has become the latest space for drug screening in the world at present. Intestinal probiotics is another way to treat intestinal pathogenic microbial infections such as O157:H7, which has its advantages over antibiotics, including the lack of drug resistance. Moreover, the H24 strain studied in this paper is a probiotics which has universal preventive, therapeutic or auxiliary therapeutic effect on diarrhea in chickens, pigs, cattle and other animals. The strain has been identified as Bacillus amylopectin (Bacillus amyloliquefaciens). In this paper. In this study, the natural fermentation products of H24 were extracted under the guidance of quartile induction theory, and the inhibitory effect of the natural strain on enterohemorrhagic Escherichia coli O157:H7 strain Sakai was studied by (in vivo) in vitro (in vitro),. In vitro experiments included the inhibitory effect of H24 natural fermentation products on biofilm formation of Sakai strain and the inhibitory effect on the expression of Shiga toxin of Sakai strain. The formation of O157 biofilm and the expression of Shiga toxin are indirectly controlled by the QS system of the pathogen, and these two indexes are also an important part of the pathogenicity of the pathogen.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R371
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