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附屬基因調(diào)節(jié)系統(tǒng)(agr)-Ⅰ型對(duì)表皮葡萄球菌生物膜形成調(diào)節(jié)關(guān)系的研究

發(fā)布時(shí)間:2018-04-20 06:13

  本文選題:表皮葡萄球菌 + 生物膜。 參考:《復(fù)旦大學(xué)》2005年博士論文


【摘要】:表皮葡萄球菌曾被認(rèn)為是皮膚、粘膜的正常菌群,近幾年來(lái),它已成為醫(yī)院內(nèi)感染的最重要的病原體之一。表皮葡萄球菌產(chǎn)生很少的組織損傷性酶和毒素,致病機(jī)理與其能黏附在高分子材料表面并生成生物膜有關(guān)。研究調(diào)節(jié)表皮葡萄球菌生物膜形成的相關(guān)基因,闡明表皮葡萄球菌生物膜形成的調(diào)節(jié)機(jī)制是研究預(yù)防和治療由表皮葡萄球菌引起的插管等留置物相關(guān)感染的關(guān)鍵。 葡萄球菌的agr是最重要的毒力因子調(diào)節(jié)系統(tǒng),負(fù)責(zé)對(duì)毒力因子生長(zhǎng)階段依賴性的調(diào)節(jié)。目前人們已逐漸認(rèn)識(shí)到表皮葡萄球菌的agr基因在其致病中的重要性,如agr可以下調(diào)和生物膜形成最初階段有關(guān)的重要的結(jié)構(gòu)基因-atlE的表達(dá);agr可以產(chǎn)生一種轉(zhuǎn)錄后修飾的多肽信息素,信息素能活化自身的agr,但能抑制非自身的agr等等。但與金黃色葡萄球菌相比,目前對(duì)表皮葡萄球菌的agr基因功能研究才剛剛開(kāi)始,許多疑問(wèn)尚待解決。本研究目的是對(duì)表皮葡萄球菌agr基因的功能、agr基因與表皮葡萄球菌生物膜形成之間的關(guān)系、agr基因?qū)ι锬ば纬烧{(diào)節(jié)的機(jī)制等進(jìn)行較為全面的研究,最終希望明確agr基因與表皮葡萄球菌致病性之間的關(guān)系,為進(jìn)一步研究如何治療臨床上頑固的表皮葡萄球菌感染及藥物的合理應(yīng)用提供新的思路。 (1) 我國(guó)表皮葡萄球菌agr多態(tài)性分布情況 agr在葡萄球菌中呈多態(tài)性。對(duì)金黃色葡萄球菌的研究認(rèn)為agr亞型與其所致疾病之間存在相關(guān)性。本文通過(guò)特異性PCR及酶切鑒定、序列測(cè)定的方法對(duì)不同來(lái)源的表皮葡萄球菌進(jìn)行亞型分布的研究,結(jié)果表明病原性表皮葡萄球菌以agr-Ⅰ型為主,特別是導(dǎo)管和血液來(lái)源的表皮葡萄球菌agr-Ⅰ型占有比例最高,臨床資料也提示與導(dǎo)管植入和菌血癥有關(guān)的表皮葡萄球菌感染是臨床上最為嚴(yán)重的表皮葡萄球菌感染類型。正常菌株以agr-Ⅱ型為主。對(duì)表皮葡萄球菌agr基因及其亞型分布的研究,對(duì)接下來(lái)研究表皮葡萄球菌agr-Ⅰ型基因功能、agr-Ⅰ型基因與表皮葡萄球菌生物膜形成之間的關(guān)系等方面將起著十分重要的作用。 (2) 表皮葡萄球菌agr-Ⅰ型陰性突變株的建立 表皮葡萄球菌agr與生物膜形成有關(guān)的重要結(jié)構(gòu)基因之間,目前已發(fā)現(xiàn)表皮葡萄球菌agr基因可以下調(diào)與生物膜形成最初階段有關(guān)的重要的結(jié)構(gòu)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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