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標題: | 胞外去氧核醣核酸在感染性心內膜炎中對轉糖鏈球菌形成生物膜所扮演之角色 Role of Extracellular DNA in Streptococcus mutans Biofilm Formation in Infective Endocarditis |
作者: | Yang Li 李泱 |
指導教授: | 賈景山 |
關鍵字: | 胞外去氧核醣核酸,生物膜,感染性心內膜炎, extracellular DNA,biofilm,infective endocarditis, |
出版年 : | 2011 |
學位: | 碩士 |
摘要: | 生物膜形成能力在轉糖鏈球菌(Streptococcus mutans)引起高致死率感染性心內膜炎(infective endocarditis)之致病機制中扮演重要角色。血液中的轉糖鏈球菌,可黏附到受傷的瓣膜上形成贅疣(vegetation),進一步引起感染性心內膜炎,但到目前為止,對於贅疣形成之詳細機制仍不清楚。近年研究顯示,許多細菌會藉由調控自體溶解(autolysis)之活性,以放出胞外去氧核醣核酸(extracellular DNA,eDNA)幫助細菌形成生物膜;而嗜中性白血球胞外網狀結構(neutrophil extracellular traps,NETs)已被證實會抓住並活化血小板,進而促進血栓形成,顯示NETs可能也參與在贅疣形成機制中。因此,本篇研究便是要進一步探討細菌eDNA及NETs對於轉糖鏈球菌在感染性心內膜炎中形成生物膜所扮演的角色。在大鼠感染性心內膜炎動物模式中,發現贅疣上同時有細菌eDNA及NETs的存在。體外生物膜形成能力分析結果發現,鈣離子可刺激轉糖鏈球菌之eDNA釋放並促進細菌生物膜形成,而經自體溶解蛋白抑制劑PAS(polyanetholesulfonic acid)及DNase I處理後,也發現可有效抑制轉糖鏈球菌形成生物膜之能力,說明轉糖鏈球菌藉由自體溶解所放出之eDNA在體外形成生物膜中扮演重要角色。此外,在模擬體內生物膜形成之體外模式中加入嗜中性白血球,可觀察到有NETs的釋放並造成轉糖鏈球菌生物膜增厚之現象; DPI及DNase I可明顯抑制生物膜增厚之現象。此外,進一步利用對大鼠感染性心內膜炎動物模式給予DNase I,結果發現靜脈注射DNase I可抑制贅疣上NETs形成,並降低贅疣細菌數目及贅疣大小。綜合本篇實驗結果,證明細菌的eDNA及NETs皆參與在感染性心內膜炎中轉糖鏈球菌形成生物膜之過程,對於未來發展感染性心內膜炎之治療方法上,提供了新的策略。 Biofilm is an important virulence trait for Streptococcus mutans to cause infective endocarditis (IE) which is an infectious disease with high recurrence and mortality rate. After entering into bloodstream, S. mutans can adhere to the injured valve and form vegetation, a compact fibrin-platelet bacterial biofilm, to cause IE. So far, the mechanism of vegetation formation remains unclear. It has been evidenced that extracellular DNA (eDNA) released via bacteria lysis, is required for bacteria biofilm formation, and neutrophil extracellular traps (NETs) could promote thrombosis by trapping and activating platelets, which may facilitate the vegetation formation. Therefore, we hypothesize that both bacterial eDNA and NETs may be involved in S. mutans biofilm formation on the injured valve. In the rat experimental IE model, we found that both bacterial eDNA and NETs exist in vegetation. The calcium ions could enhance S. mutans biofilm formation and eDNA releasing in the in vitro biofilm assay, and the enhancement could be inhibited by PAS and DNase I treatment. Neutrophils could enhance S. mutans biofilm formation in platelet-rich plasma and this effect could be inhibited by DPI and DNase I treatment. Administration of the bovine pancreatic DNase I could reduce the NETs formation, vegetation size and colonized bacterial number in the rat experimental IE model. Taken together, these results suggest that both bacterial eDNA and NETs play important roles in S. mutans biofilm formation in vitro and in the rat experimental IE model. These results provide important information for developing new strategies for controlling IE. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/38296 |
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顯示於系所單位: | 微生物學科所 |
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