NHLBI MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

感染性心内膜炎是最常见的严重和危及生命的疾病。 美国的心脏感染。预计病例数量 增加是因为静脉注射吸毒者的数量不断增加 都面临着疾病发展和老年人口增加的风险 有潜在瓣膜退行性改变的个人，他们也在 疾病发展的风险。有相当大比例的 这些病例是由绿色链球菌引起的，通常 血链球菌和变形链球菌。一般的非侵入性 变形链球菌是引起龋齿的变形链球菌的一员， 是最常见的变形链球菌种类，分离自 人类的口腔。这项研究的长期目标是扩大 对口腔感染性心内膜炎发病机制的认识 链球菌。这个项目的目标是确定和描述 参与细菌黏附的细菌细胞表面分子 变形链球菌对心脏组织的作用。这个项目的具体目标是 目的：1)研究变形链球菌细胞与 细胞外基质；2)构建变形链球菌突变株 转座子突变，其结合纤维连接蛋白的能力存在缺陷； 3)探讨变形链球菌结合纤维连接蛋白在感染性疾病中的作用。 在实验性心内膜炎模型中测定心内膜炎 纤维连接蛋白结合缺陷突变株的毒力比较 正常纤维连接蛋白结合的胞外和细胞膜蛋白 变形链球菌细胞和纤维连接蛋白结合缺陷变形链球菌细胞和5) 纤维连接蛋白结合编码基因的克隆与鉴定 变形链球菌细胞表面的受体。

Infective endocaditis is the most common serious and life-threatening cardiac infection in the United States. The number of cases is expected to increase because of the increasing number of intravenous drug users who are at risk for the development of the disease and the increase in elderly individuals with underlying valvular degenerative changes who also are at risk for the development of the disease. A significant percentage of these cases are caused by members of the viridans streptococci, typically Streptococcus sanguis and Streptococcus mutans. The generally noninvasive S. mutans is a member of the dental caries-causing mutans streptococci and is the most frequent species of the mutans streptococci isolated from the oral cavity of humans. The long-term goal of this study is to broaden the understanding of the pathogenesis of infective endocarditis caused by oral streptococci. The goal of this project is to identify and characterize the bacterial cell surface molecules that are involved in the adherence of mutans streptococci to heart tissue. The specific aims of this project are: 1) to characterize the binding and adherence of S. mutans cells to extracellular matrix; 2) to construct S. mutans mutant strains using transposon mutagenesis with defects in their ability to bind fibronectin; 3) to evaluate the role of fibronectin-binding by S. mutans in infective endocarditis by determining in a model of experimental endocarditis the virulence of fibronectin-binding-defective mutant strains; 4) to compare the extracellular and cell membrane proteins of normal fibronectin-binding S. mutans cells and fibronectin-binding-defective S. mutans cells and 5) to clone and characterize the gene encoding the fibronectin-binding receptor on the surface of S. mutans cells.