ROLE OF CELLWALL COMPONENTS IN ENTEROCOCCAL ENDOCARDITIS

描述(摘自摘要)：肠球菌是引起肺炎的重要病原体 一种特别严重的细菌性心内膜炎，以及其他 感染。他们现在是世界上最大的三种医院病原体之一 我们。由肠球菌引起的感染是出了名的顽固 抗生素治疗，对遗传和疾病知之甚少 这组细菌毒力的分子基础。这 申请寻求继续支持调查两个人的角色 肠球菌性心内膜炎的细胞壁成分。一个组件是 称为聚集物质(AS)的质粒编码的蛋白质，以及第二种 是一种称为肠球菌结合物质的染色体编码因子 (EBS)，可能含有脂磷壁酸作为其主要成分。因为- 细菌细胞之间需要EBS结合才能形成交配对 正在进行接合的质粒转移。我们的数据表明，AS和 EBS对实验性动物模型肠球菌毒力的影响 心内膜炎。这些化合物中的一种或两种也可能是一种毒素 对严重心内膜炎病例的致命性负责。四个 以下列出的项目的具体目标旨在更好地定义 AS和EBS作为毒力因子的作用，并识别重要的 这些分子中的结构/功能关系。具体目标： 1)确定细菌因子的分子同一性 严重实验性心内膜炎感染的致死性。2)确定 目标1中确定的毒素导致致死的机制。3) 确定AS和EBS所需的关键结构特征 通过这些分子增强毒力。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.