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 心脏感染在美国 预计病例数 因为越来越多的静脉吸毒者， 有患上这种疾病的风险， 患有潜在瓣膜退行性变化且同时处于 疾病发展的风险。 相当比例的 这些病例是由草绿色链球菌引起的， 血链球菌和变形链球菌。 一般非侵入性 S.变形链球菌是引起龋齿的变形链球菌的成员， 是最常见的变种链球菌分离的物种， 人类的口腔 这项研究的长期目标是扩大 口服抗生素致感染性心内膜炎的发病机制 链球菌。 该项目的目标是识别和表征 参与粘附的细菌细胞表面分子 变异链球菌感染到心脏组织 该项目的具体目标 主要是：1）表征S.变形细胞， 2）构建S.变异株， 转座子诱变，其结合纤连蛋白的能力有缺陷; 3)探讨S.感染性变形菌 通过在实验性心内膜炎模型中测定 纤连蛋白结合缺陷突变株的毒力; 4）比较 正常纤连蛋白结合的细胞外和细胞膜蛋白 S.变形细胞和纤连蛋白结合缺陷型S.变形细胞和5） 克隆和表征编码纤连蛋白结合的基因， S.变形细胞

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.