NHLBI MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

NHLBI 少数族裔学校教师发展奖

• 批准号: 2415475
• 负责人: ROBERT G HOLT
• 金额: $ 8.63万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-22 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415475
• 关键词: Streptococcus mutans; bacterial endocarditis; disease /disorder model; extracellular; fibronectins; laboratory rabbit; laboratory rat; membrane proteins; minority institution research support; oral bacteria; pathology; receptor binding; transposon /insertion element

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.

感染性内部炎是最常见的严重和威胁生命的 美国心脏感染。 预计案件数量 由于静脉吸毒者的数量增加而增加 有疾病发展的风险和老年人的增加 具有基础瓣膜退化性变化的个体也在 疾病发展的风险。 很大的百分比 这些情况是由Viridans链球菌成员引起的，通常是 链球菌和链球菌突变。 通常无创的 S. mutans是牙齿引起的龋齿的成员，链球菌和 是从从链球菌中分离出的最常见的属性物种 人类口腔。 这项研究的长期目标是扩大 了解口腔引起的感染性心内膜炎的发病机理 链球菌。 该项目的目的是识别和表征 与依从性有关的细菌细胞表面分子 突变链球菌链球菌。 该项目的具体目的 是：1）表征链球菌细胞与 细胞外基质； 2）使用 转座子诱变具有缺​​陷，其结合纤连蛋白的能力； 3）评估链球菌在感染性的纤连蛋白结合的作用 心内膜炎通过在实验性心内膜炎模型中确定 纤连蛋白结合缺陷性突变菌株的毒力； 4）比较 正常纤连蛋白结合的细胞外膜和细胞膜蛋白 S. mutans细胞和纤连蛋白结合缺陷的链球菌细胞和5） 克隆并表征编码纤连蛋白结合的基因 链球菌细胞表面的受体。