Staphylococcus aureus RNA turnover properties

描述（由申请人提供）：金黄色葡萄球菌是医院和社区获得性感染的主要原因。这种生物体之所以能够致病，是因为它产生了一系列毒力因子和抗生素耐药性决定因素，以及它对环境挑战的适应性。我们的长期目标是定义控制S的监管机制。金黄色葡萄球菌致病性经典，S。金黄色葡萄球菌毒力因子的表达被认为是在转录物合成水平上受到调节。这个建议的具体假设是S。金黄色葡萄球菌通过调节它们的mRNA周转来调节这些因子。这一假说是基于以下观察：1）我们已经表明，葡萄球菌辅助调节因子（sarA）稳定毒力因子转录的方式与蛋白质的生产呈负相关，2）我们的初步数据表明，诱导S。金黄色葡萄球菌应激反应导致mRNA周转的整体改变，3）我们已经表明mRNA衰减的改变与蛋白质产生的变化相关。4)mRNA周转的调节是其他细菌病原体中调节蛋白质产生的常见机制。具体目标是：1.描述影响对数相位S的因素。金黄色葡萄球菌mRNA周转。我们相信，正常的RNA周转机制的功能可以改变响应内源性和外源性的线索。作为确定这些功能如何改变的先决条件，了解天然RNA周转中涉及的主要成分至关重要。2.表征调节mRNA稳定性对蛋白质产生的影响。我们将评估应激介导的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周转的因素。小的非编码RNA分子（sRNA）和RNA结合蛋白影响细菌mRNA的周转和翻译。我们已经确定S。金黄色葡萄球菌以生长期和/或应激依赖性方式产生139种sRNA样分子。我们将描述这些分子对S.金黄色葡萄球菌mRNA周转和蛋白质产生。此外，我们将确定额外的反式作用因子，瞬时改变S。金黄色葡萄球菌毒力因子mRNA周转。金黄色葡萄球菌是医院和社区获得性感染的主要原因。本提案的目标是研究生物体调节其毒力因子库并导致疾病的机制。明确这些机制有望为S.金黄色葡萄球菌感染

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.