ROLE OF CELLWALL COMPONENTS IN ENTEROCOCCAL ENDOCARDITIS

描述（来自摘要）：肠球菌是重要的病原体， 特别严重的细菌性心内膜炎，以及其他 感染. 它们现在是世界上三大医院病原体之一。 我们 由肠球菌引起的感染是众所周知的， 抗生素治疗，而对遗传和 这组细菌毒性的分子基础。 这 申请寻求继续支持调查两名 肠球菌性心内膜炎的细胞壁成分。 一种组分是 质粒编码的蛋白质称为聚集物质（AS）， 是一种染色体编码因子，称为肠球菌结合物质， (EBS)其主要成分可能是脂磷壁酸。 AS- 细菌细胞之间形成配对需要EBS结合 进行接合质粒转移。 我们的数据表明，AS和 肠球菌在实验动物模型中对肠球菌毒力的影响 心内膜炎 这些化合物中的一种或两种也可能是毒素 在严重的心内膜炎病例中是致命的。 四 以下所列项目的具体目标旨在更好地界定 AS和EBS作为毒力因子的作用，并确定重要 结构/功能关系。 具体目标： 1)确定负责的细菌因子的分子身份 严重实验性心内膜炎感染的致死率。 2)确定 目标1中确定的毒素导致致死的机制。 第三章 确定所需的AS和EBS的关键结构特征， 增强这些分子的毒力。 4)通过以下方式确定机制 其中AS的表达是在体内诱导的。

DESCRIPTION (from Abstract): Enterococci are important causative agents of a particularly serious form of bacterial endocarditis, as well as other infections. They are now among the top three nosocomial pathogens in the US. Infections caused by the enterococci are notoriously recalcitrant to antibiotic treatment, and relatively little is known about the genetic and molecular basis for the virulence of this group of bacteria. This application seeks continued support for investigation of the role of two cell wall components in enterococcal endocarditis. One component is a plasmid- encoded protein called Aggregation Substance (AS), and the second is a chromosomally-encoded factor called Enterococcal Binding Substance (EBS), which probably contains Lipoteichoic acid as its main component. AS- EBS binding is required to form a mating pair between bacterial cells undergoing conjugative plasmid transfer. Our data suggest that both AS and EBS contribute to Enterococcal Virulence in an experimental animal model of endocarditis. One or both of these compounds may also be a toxin responsible for lethality in severe cases of endocarditis. The four Specific Aims of the project listed below are designed to better define the roles of AS and EBS as virulence factors, and to identify important structure/function relationships in these molecules. SPECIFIC AIMS: 1)Determine the molecular identity of the bacterial factor responsible for lethality in severe experimental endocarditis infections. 2) Determine the mechanism by which the Toxin identified in Aim 1 causes lethality. 3) Determine the key structural features of AS and EBS required for the enhancement of virulence by these molecules. 4) Determine the mechanism by which expression of AS is induced in vivo.