轉糖鏈球菌表面蛋白在感染性心內膜炎中贅疣形成之角色

Abstract

感染性心內膜炎是一種高致死率高復發率的心血管感染疾病，轉糖鏈球菌屬於會造成伺機性感染性心內膜炎感染的草綠色鏈球菌之其中一員，而血漿中的成分以及細菌的表面蛋白之間的交互作用在贅疣的形成中扮演著很重要的角色，因此我們使用已建立好的感染性心內膜炎的動物模型，來研究轉糖鏈球菌的表面蛋白在動物體內中形成贅疣的重要性。結果顯示了當使用乳膠小珠(latex beads)來攜帶轉糖鏈球菌表面的相關蛋白時，確實會造成贅疣的形成;反之，攜帶牛血清蛋白的乳膠小珠則不會造成贅疣的產生;另外我們使用了電子顯微鏡及螢光染色的方式在贅疣中觀察到乳膠小珠的存在。而在細菌的表面蛋白中，纖維蛋白原以及纖維結合素的結合蛋白，在抵抗白血球的吞噬作用以及促使細菌黏附到心臟瓣膜上，都佔有相當重要的功能，也因此我們可藉由動物實驗，來研究轉糖鏈球菌其中一個具有纖維蛋白原以及纖維結合素結合蛋白的表面蛋白，Fngb。當和野生株GS5相比較時，fngb的突變株會造成比較輕微的感染性心內膜炎，此外贅疣也比較小且分離出的細菌也較少，這些結果證實了細菌的表面蛋白在贅疣形成確實扮演了重要的角色。

Infective endocarditis (IE) is an infectious disease of the cardiovascular system, and carries a high recurrence and mortality rate. Streptococcus mutans, a member of viridans streptococci, is one of the major opportunistic pathogens for causing IE. The interactions of plasma components with bacterial surface proteins play important roles in vegetation formation. Using experimental infective endocarditis rat model, we investigated the role of bacterial surface proteins in vegetation formation in vivo. Latex beads coated with cell-wall assaciated proteins of S. mutans could induce vegetaion formation directly; in contrast latex beads coated with bovine serum albumin could not. The beads could be detected in vegetation by transmisson electron microscope and immunofluorescent staining. Among bacterial surface proteins, fibrinogen and fibronetin binding proteins are important for bacteria escaping from leukocyte phagocytosis and attachment to heart valve. Fngb, one of S. mutans fibrinogen (fibronectin) binding proteins, was also studied in vivo. When compared with wild type strain, the fngb mutant caused milder infective endocarditis. Vegetation in smaller size and less number of bacteria colonized was isolated from fngb null mutant induced vegetation. These results demonstrated bacterial surface protein play an important role in vegetation formation in vivo.