附属基因调节系统（agr）-Ⅰ型对表皮葡萄球菌生物膜形成调节关系的研究

发布时间：2018-04-20 06:13

  本文选题：表皮葡萄球菌 + 生物膜　； 参考：《复旦大学》2005年博士论文

【摘要】：表皮葡萄球菌曾被认为是皮肤、粘膜的正常菌群,近几年来,它已成为医院内感染的最重要的病原体之一。表皮葡萄球菌产生很少的组织损伤性酶和毒素,致病机理与其能黏附在高分子材料表面并生成生物膜有关。研究调节表皮葡萄球菌生物膜形成的相关基因,阐明表皮葡萄球菌生物膜形成的调节机制是研究预防和治疗由表皮葡萄球菌引起的插管等留置物相关感染的关键。 葡萄球菌的agr是最重要的毒力因子调节系统,负责对毒力因子生长阶段依赖性的调节。目前人们已逐渐认识到表皮葡萄球菌的agr基因在其致病中的重要性,如agr可以下调和生物膜形成最初阶段有关的重要的结构基因-atlE的表达;agr可以产生一种转录后修饰的多肽信息素,信息素能活化自身的agr,但能抑制非自身的agr等等。但与金黄色葡萄球菌相比,目前对表皮葡萄球菌的agr基因功能研究才刚刚开始,许多疑问尚待解决。本研究目的是对表皮葡萄球菌agr基因的功能、agr基因与表皮葡萄球菌生物膜形成之间的关系、agr基因对生物膜形成调节的机制等进行较为全面的研究,最终希望明确agr基因与表皮葡萄球菌致病性之间的关系,为进一步研究如何治疗临床上顽固的表皮葡萄球菌感染及药物的合理应用提供新的思路。 (1) 我国表皮葡萄球菌agr多态性分布情况 agr在葡萄球菌中呈多态性。对金黄色葡萄球菌的研究认为agr亚型与其所致疾病之间存在相关性。本文通过特异性PCR及酶切鉴定、序列测定的方法对不同来源的表皮葡萄球菌进行亚型分布的研究,结果表明病原性表皮葡萄球菌以agr-Ⅰ型为主,特别是导管和血液来源的表皮葡萄球菌agr-Ⅰ型占有比例最高,临床资料也提示与导管植入和菌血症有关的表皮葡萄球菌感染是临床上最为严重的表皮葡萄球菌感染类型。正常菌株以agr-Ⅱ型为主。对表皮葡萄球菌agr基因及其亚型分布的研究,对接下来研究表皮葡萄球菌agr-Ⅰ型基因功能、agr-Ⅰ型基因与表皮葡萄球菌生物膜形成之间的关系等方面将起着十分重要的作用。 (2) 表皮葡萄球菌agr-Ⅰ型阴性突变株的建立 表皮葡萄球菌agr与生物膜形成有关的重要结构基因之间,目前已发现表皮葡萄球菌agr基因可以下调与生物膜形成最初阶段有关的重要的结构基因atlE
[Abstract]:Staphylococcus epidermidis was once regarded as the normal flora of skin and mucous membrane. In recent years, Staphylococcus epidermidis has become one of the most important pathogens of nosocomial infection. Staphylococcus epidermidis produces few tissue damage enzymes and toxins, which is related to the adhesion of Staphylococcus epidermidis to the surface of polymer and the formation of biofilm. To study the genes related to the biofilm formation of Staphylococcus epidermidis and to elucidate the regulatory mechanism of biofilm formation of Staphylococcus epidermidis is the key to the prevention and treatment of staphylococcus epidermidis infection caused by staphylococcus epidermidis. Staphylococcus agr is the most important virulence factor regulation system, responsible for the virulence factor growth phase dependent regulation. The importance of the agr gene of Staphylococcus epidermidis in the pathogenesis of Staphylococcus epidermidis has been gradually recognized. For example, agr can down-regulate the expression of an important structural gene -atlE related to the initial stage of biofilm formation. It can produce a post-transcriptional modified polypeptide pheromone, which can activate its own agronomy, but inhibit non-self agr, and so on. But compared with Staphylococcus aureus, the study of agr gene function of Staphylococcus epidermidis is just beginning, and many questions remain to be solved. The purpose of this study was to investigate the relationship between agr gene function and biofilm formation of Staphylococcus epidermidis. Finally, we hope to clarify the relationship between agr gene and pathogenicity of Staphylococcus epidermidis, and provide a new idea for further study on the treatment of clinical stubborn Staphylococcus epidermidis infection and rational use of drugs. Distribution of agr Polymorphism of Staphylococcus epidermidis in China Agr is polymorphic in Staphylococcus. The study of Staphylococcus aureus suggests that there is a correlation between the subtype of agr and the disease caused by Staphylococcus aureus. The distribution of subtypes of Staphylococcus epidermidis from different sources was studied by specific PCR, enzyme digestion and sequencing. The results showed that the main pathogenic Staphylococcus epidermidis was agr- 鈪，

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