鼠疫耶尔森氏菌和宿主相互作用的体内转录谱研究

发布时间：2018-01-04 07:09

本文关键词：鼠疫耶尔森氏菌和宿主相互作用的体内转录谱研究　出处：《中国人民解放军军事医学科学院》2007年博士论文　论文类型：学位论文

【摘要】： 鼠疫耶尔森氏菌(以下简称鼠疫菌)是鼠疫的病原体，，主要引发三种类型的鼠疫：腺鼠疫、肺鼠疫和败血症型鼠疫。肺鼠疫具有传染性强和致死率高的特点。在自然界中，鼠疫菌通常在啮齿类动物和跳蚤间相互传播并进行保存；因此鼠疫菌在其生活周期中要适应跳蚤前胃以及啮齿动物体内的微环境变化(温度、pH值、离子强度等)才能生存。鼠疫菌利用复杂高效的转录调控机制来应对这种环境条件的剧烈变化，实现其传播和致病能力。感染性疾病的发生实际上是病原体与宿主相互作用的一个互动过程。在此期间，既有病原体为逃避宿主防御机制而进行的改变，也有宿主为清除病原体而调动防御体系的努力。本课题通过建立小鼠经鼻内感染鼠疫菌的动物模型，模拟鼠疫菌在自然感染过程中经历的温度改变及气溶胶传播的过程；在感染后不同时间点进行病理学观察；利用逆转录-定量PCR技术研究鼠疫菌重要基因(毒力因子、整体调控因子、转录因子、双组分调控系统、密度感应系统等)在致病过程中的转录变化；并利用芯片技术研究感染过程中小鼠的全局性转录组学变化。本研究首先建立了肺鼠疫的动物感染模型，并获得了鼠疫感染过程中的系统病理学资料，结果显示鼠疫菌感染在宿主体内呈现典型的肺鼠疫发展过程，根据肺组织的病理学变化将感染分为三个时期：早期、中期和晚期。鼠疫菌的转录谱数据提供了鼠疫菌部分调控基因在体内的转录动态变化；确定了不同感染时期和不同组织中调控基因的转录差异变化；并与体外(26℃)转录水平进行比较，对鼠疫菌重要基因在感染过程中发生的转录调节进行分析，初步探讨这些基因在鼠疫菌致病过程中发挥的作用及可能参与的机制。小鼠的全局性转录组数据显示肺鼠疫早期和晚期及不同组织小鼠具有不同的基因表达模式；感染晚期大量基因发生转录调节，并表现为全局性转录下调。综合上述结果，初步分析了小鼠肺鼠疫发展过程中，组织病理学改变与鼠疫菌基因以及宿主相应基因的转录变化之间的相关性；初步探讨了鼠疫菌部分调控基因在感染过程中发挥的作用及可能参与的致病机制；并在转录水平上从宿主和病原体相互作用的角度探究鼠疫菌的致病机制。
[Abstract]:Jerson S (hereinafter referred to as the plague bacterium Yersinia pestis) is the pathogen of plague, the plague caused mainly three types: bubonic plague, pneumonic and septicemic plague. Pneumonic plague is contagious and strong death rate is high. In nature, usually in rodent animal plague and flea transmitted and saved; therefore, Yersinia pestis in the life cycle to adapt to the stomach in rodents and flea micro environmental changes (temperature, pH value, ionic strength etc.) to survive. Dramatic changes in the mechanism of transcriptional regulation of Yersinia pestis by complex and efficient to deal with the environmental conditions, the propagation and pathogenicity.
The occurrence of infectious diseases is actually a process of interaction between pathogen and host interaction. During this period, both pathogens to evade host defense mechanisms of change, also have to clear the pathogen and the host defense system to mobilize efforts. This paper through the establishment of the animal model of mice infected with plague bacteria in the nose, process temperature and the change of aerosol transmission simulation experience in Yersinia pestis during natural infection; the pathologic changes were observed in different time after infection; using reverse transcriptase quantitative PCR of Yersinia pestis gene (an important virulence factor, the overall regulatory factor, transcription factor, two-component regulatory system, quorum sensing system) changes in transcription in the pathogenic process; and the global transcriptome microarray in mice during infection changes.
This research has established the pneumonic plague infected animal model and obtain the system in the process of plague infection pathological data, results show that the typical development process in the host of pneumonic plague bacteria infection, according to the pulmonary pathological changes of infection will be divided into three periods: early, middle and late data. Provides some regulatory genes in Yersinia pestis transcription in vivo transcription dynamics of plague bacteria spectrum; determine the changes of transcription regulation differences in different infection stages and different tissues and in vitro gene; and (26 C) compared to the level of transcription, transcription of important gene of Yersinia pestis in the infection process regulation analysis, preliminary to explore the mechanism of these genes play in the pathogenesis of Y.pestis in effect and may be involved in mice. The global transcriptome data show that early and late lung plague in different tissues and small Rats with different patterns of gene expression; gene transcription occurs late a lot of infection, and the performance for the global transcription down. From the above results, a preliminary analysis of the plague in mice in the process of development, change and correlation between transcriptional changes of Yersinia pestis genes and the corresponding genes of host tissue pathology; preliminary study on pathogenic mechanism play a part regulation of gene of Yersinia pestis role during infection and may be involved in the pathogenesis of; and at the level of transcription from the host pathogen interaction perspective of Yersinia pestis.

【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R378

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