Genetic Analysis of S. Pyogenes Virulence Factors

化脓性链球菌毒力因子的遗传分析

• 批准号: 6804579
• 负责人: June R Scott
• 金额: $ 39.57万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-06-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6804579
• 关键词: Streptococcus pyogenes; bacterial genetics; bacterial proteins; binding sites; gene expression; genetic regulation; genetic regulatory element; laboratory mouse; microarray technology; operon; phosphorylation; polymerase chain reaction; protein binding; protein protein interaction; site directed mutagenesis; virulence

Streptococcus pyogenes, the group A streptococcus (GAS) is an important human pathogen causing frequent self-limiting diseases which may lead to serious sequelae. In addition, the GAS seems to be "reemerging" as a cause of life-threatening invasive disease. Because of the great diversity of syndromes produced by many strains of GAS, we wish to improve our understanding of the pathogenesis of this organism by focusing on the regulation of expression of its genes, which presumably occurs on interaction with the human host to determine disease outcome. This proposal focuses on the two major global regulators that alter expression of many GAS proteins, including virulence factors. The regulation of expression of Mga (Aim 1) and CovR/S (CsrR/S) (Aim 3) will be studied. The genes controlled by Mga and CovR/S and the mechanisms by which these regulatory proteins control expression of these genes will also be investigated (Aims 2 and 4). We hope these analyses will improve our understanding at the molecular level of the interactions of GAS with its human host and may identify new targets for development of therapies and vaccines.

链球菌为链球菌，A组链球菌（气）是一种重要的人病，导致频繁的自限性疾病，可能导致严重的后遗症。此外，气体似乎正在“重新出现”作为威胁生命的侵入性疾病的原因。由于许多气体菌株产生的综合征多样性，我们希望通过关注其基因表达的调节来提高对这种生物体的发病机理的理解，其基因的表达可能发生在与人类宿主相互作用以确定疾病结果。该提案着重于改变许多气体蛋白（包括毒力因子）的两个主要全球调节剂。将研究MGA（AIM 1）和COVR/S（CSRR/S）（AIM 3）的表达调节。由MGA和COVR/S控制的基因以及这些调节蛋白控制这些基因表达的机制也将 被调查（目标2和4）。我们希望这些分析能够提高我们在气体与人类宿主相互作用的分子水平上的理解，并可以确定疗法和疫苗开发的新目标。