Staphylococcus aureus RNA turnover properties

金黄色葡萄球菌 RNA 周转特性

基本信息

批准号：
7383346
负责人：
Paul Dunman
金额：
$ 37.13万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2012-08-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7383346
关键词：
Acids Antibiotic Resistance Antimicrobial Resistance Bacillus subtilis Biochemical Biological Assay Cells Community Hospitals Community-Acquired Infections Complex Condition Cues Data Development Disease Endocarditis Escherichia coli Functional RNA Goals Growth Half-Life Heat-Shock Response Individual Infection Infectious Skin Diseases Libraries Life Link Measures Mediating Messenger RNA Molecular Organism Pathogenesis Pathogenicity Phase Platelet Factor 4 Production Property Proteins Proteomics RNA RNA Degradation RNA degradosome RNA-Binding Proteins Range Reporting Severities Shock Son of Sevenless Proteins Staphylococcus aureus Stress Therapeutic Intervention Trans-Activators Transcript Translations Virulence Factors Western Blotting antimicrobial base biological adaptation to stress chemotherapy degradosome mRNA Decay mRNA Stability mRNA Transcript Degradation member mutant novel novel strategies pathogen promoter protein degradation response

项目摘要

DESCRIPTION (provided by applicant): Staphylococcus aureus is a leading cause of nosocomial and community acquired infections. The organism owes its ability to cause disease to the production of a repertoire of virulence factors and antibiotic resistance determinants, as well as its adaptability to environmental challenges. Our long- term goal is to define the regulatory mechanisms controlling S. aureus pathogenicity. Classically, S. aureus virulence factor expression has been considered to be regulated at the level of transcript synthesis. The specific hypothesis of this proposal is that S. aureus regulates these factors by modulating their mRNA turnover. This hypothesis is based on the following observations: 1) we have shown that the staphylococcal accessory regulator (sarA) stabilizes virulence factor transcripts in a manner that inversely correlates with protein production, 2) our preliminary data indicates that induction of S. aureus stress responses cause global alterations in mRNA turnover, 3) we have shown that alterations in mRNA decay correlate with changes protein production. 4) Modulation of mRNA turnover is a common mechanism of regulating protein production in other bacterial pathogens. The specific aims are to: 1. Characterize factors that influence log-phase S. aureus mRNA turnover. We believe that the normal RNA turnover machinery functions can be altered in response to endogenous and exogenous cues. As a prerequisite to determining how these functions are altered, it is crucial to understand the principle components involved in native RNA turnover. 2. Characterize the effects of modulating mRNA stability on protein production. We will assess the functional significance of stress mediated changes in mRNA stability on virulence factor protein production. 3. Identify factors that transiently modulate mRNA turnover. Small non-coding RNA molecules (sRNAs) and RNA binding proteins influence bacterial mRNA turnover and translation. We have determined that S. aureus produces 139 sRNA-like molecules in a growth phase- and/or stress- dependent manner. We will characterize the effects of these molecules on S. aureus mRNA turnover and protein production. Moreover, we will identify additional trans-acting factors that transiently alter S. aureus virulence factor mRNA turnover. Staphylococcus aureus is a leading cause of hospital and community acquired infections. The goal of this proposal is to investigate the mechanism(s) by which the organism, regulates its repertoire of virulence factors and causes disease. Defining these mechanisms is expected to provide novel strategies for therapeutic intervention of S. aureus infections.

描述（由申请人提供）：金黄色葡萄球菌是医院和社区获得感染的主要原因。该有机体的能力归因于产生毒力因子和抗生素耐药性决定因素的曲目及其对环境挑战的适应性。我们的长期目标是定义控制金黄色葡萄球菌致病性的调节机制。从经典上讲，金黄色葡萄球菌的毒力因子表达被认为是在转录本合成水平下受到调节的。该提议的具体假设是金黄色葡萄球菌通过调节其mRNA更新来调节这些因素。该假设基于以下观察结果：1）我们已经表明，葡萄球菌辅助调节剂（SARA）以与蛋白质产生成反相关的方式稳定毒力因子转录本，2）我们的初步数据表明，aureus应激反应的诱导诱导了MRNA的全局变化，使MRNA的全局变化，您显示了MRNA的变化。 4）mRNA更新的调节是调节其他细菌病原体中蛋白质产生的常见机制。具体目的是：1。表征影响对数的S.金黄色葡萄球菌mRNA更新的因素。我们认为，正常的RNA更新机械函数可以响应内源性和外源提示而改变。作为确定这些功能如何改变的先决条件，了解与天然RNA转换有关的原理成分至关重要。 2。表征调节mRNA稳定性对蛋白质产生的影响。我们将评估压力介导的mRNA稳定性变化对毒力因子蛋白产生的功能意义。 3。确定瞬时调节mRNA更新的因素。小的非编码RNA分子（SRNA）和RNA结合蛋白会影响细菌mRNA更新和翻译。我们已经确定金黄色葡萄球菌以生长期和/或应力依赖性方式产生139个SRNA样分子。我们将表征这些分子对金黄色葡萄球菌mRNA更新和蛋白质产生的影响。此外，我们将确定瞬时改变金黄色葡萄球菌毒力因子mRNA更新的其他跨作用因子。金黄色葡萄球菌是医院和社区获得感染的主要原因。该提案的目的是研究生物体调节其毒力因素库的机制并导致疾病。预计定义这些机制将为金黄色葡萄球菌感染提供新的策略。