空肠弯曲菌膜融合蛋白CmeA、外膜蛋白CmeC的表达、纯化与结晶筛选
发布时间：2019-03-19 17:00
【摘要】：空肠弯曲菌(Campylobacter jejuni)是最常见的导致肠炎的细菌,它也可通过神经节苷脂模拟机制导致周围神经系统自免疫紊乱的格林巴利综合征,对人类健康造成危害。临床经验表明,空肠弯曲菌在人体肠道内的生存和繁殖过程中,对四环素、红霉素和氯霉素敏感,对青霉素、大灵碱、喹啉酮和头孢霉素表现出很强的耐受性。通过对其感染过程及抗性机制的了解,有针对性地设计药物与抗体,从而减少空肠弯曲菌对人类健康的危害,成为近年来的一个较重要的课题。CmeABC系统是空肠弯曲菌中的多重耐药外排系统,在对抗生素以及胆盐的抗性中起着主要作用。CmeABC系统包括三种蛋白：细胞膜融合蛋白CmeA,细胞内膜蛋白CmeB和细胞外膜蛋白CmeC其中CmeA蛋白主要功能为连接CmeB和CmeC,帮助形成外排通道。CmeC蛋白主要是作为通道,将抗生素和胆盐等从细菌体内运到体外。外源性的抗体、药物分子可以通过作用于外膜蛋白CmeC影响到CmeABC系统的功能,所以它是一个潜在的药物作用靶点。本课题对空肠弯曲菌膜融合蛋白CmeA、外膜蛋白CmeC蛋白进行表达、纯化和结晶筛选,为以后解析CmeA, CmeC蛋白的结构、针对性地设计药物、治疗相关疾病打下基础。并可借此深入理解此类蛋白的结构与功能特征,理解CmeABC系统在空肠弯曲菌生存、增殖和感染中的作用。
[Abstract]:Campylobacter jeejunii is the most common bacteria that leads to enteritis, and it can also cause the peripheral nervous system to self-immune disorder of the Guillain-Barre syndrome through the ganglionic fat simulation mechanism, which is harmful to human health. The clinical experience shows that the Campylobacter jejuni is sensitive to tetracycline, erythromycin and chloramphenicol in the survival and reproduction of human intestinal tract. In order to reduce the harm of Campylobacter jejuni to human health, it has become a more important topic in recent years. The CmeC system is a multi-drug-resistant efflux system in Campylobacter jejuni, and plays a major role in the resistance to antibiotics and bile salts. The CmeC system consists of three proteins: the cell membrane fusion protein CmeA, the cell membrane protein CmeB and the extracellular membrane protein CmeC, wherein the main function of the CmeC protein is to connect CmeB and CmeC to help form an outer discharge channel. The CmeC protein is mainly used as a channel, and antibiotics and bile salts and the like are transported from the bacteria body to the outside. Exogenous antibodies, drug molecules, can influence the function of the CmeC system by acting on the outer membrane protein CmeC, so it is a potential drug action target. The expression, purification and crystallization of CmeC protein of Campylobacter jejuni membrane fusion protein CmeA and outer membrane protein CmeC were selected, and the structure of CmeA and CmeC protein was analyzed in order to lay the foundation for the treatment of related diseases. The structure and functional characteristics of such proteins can be further understood, and the role of the CmeC system in the survival, proliferation and infection of Campylobacter jejuni is understood.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R378
本文编号：2443718
[Abstract]:Campylobacter jeejunii is the most common bacteria that leads to enteritis, and it can also cause the peripheral nervous system to self-immune disorder of the Guillain-Barre syndrome through the ganglionic fat simulation mechanism, which is harmful to human health. The clinical experience shows that the Campylobacter jejuni is sensitive to tetracycline, erythromycin and chloramphenicol in the survival and reproduction of human intestinal tract. In order to reduce the harm of Campylobacter jejuni to human health, it has become a more important topic in recent years. The CmeC system is a multi-drug-resistant efflux system in Campylobacter jejuni, and plays a major role in the resistance to antibiotics and bile salts. The CmeC system consists of three proteins: the cell membrane fusion protein CmeA, the cell membrane protein CmeB and the extracellular membrane protein CmeC, wherein the main function of the CmeC protein is to connect CmeB and CmeC to help form an outer discharge channel. The CmeC protein is mainly used as a channel, and antibiotics and bile salts and the like are transported from the bacteria body to the outside. Exogenous antibodies, drug molecules, can influence the function of the CmeC system by acting on the outer membrane protein CmeC, so it is a potential drug action target. The expression, purification and crystallization of CmeC protein of Campylobacter jejuni membrane fusion protein CmeA and outer membrane protein CmeC were selected, and the structure of CmeA and CmeC protein was analyzed in order to lay the foundation for the treatment of related diseases. The structure and functional characteristics of such proteins can be further understood, and the role of the CmeC system in the survival, proliferation and infection of Campylobacter jejuni is understood.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R378
【共引文献】
相关博士学位论文 前1条
1 赵丽娜;基层医疗机构大肠埃希菌及肺炎克雷伯菌氟喹诺酮耐药分子流行及遗传特征研究[D];浙江大学;2015年
，本文编号：2443718
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