Early agr Activation is a Key Pathogenic Signature in Persistent MRSA Bacteremia

早期 agr 激活是持续性 MRSA 菌血症的关键致病特征

基本信息

项目摘要

DESCRIPTION (provided by applicant): Staphylococcus aureus is a predominant cause of community-acquired and nosocomial infections. In addition, it is the most common cause of skin and skin structure infections, and endocarditis, and is the second most common cause of bacteremia. Despite the use of new generation antibiotics, morbidity and mortality associated with S. aureus infections remain unacceptably high. Persistent MRSA bacteremia (PB) represents an important subset of S. aureus infections, and correlates with particularly severe outcomes. Therefore, PB presents a significant therapeutic challenge to the medical community. Understanding the relevant molecular mechanisms of PB is essential to optimize therapy against life-threatening S. aureus infections. Our preliminary data indicate that PB clinical outcomes significantly correlated with differences in key pathogenic characteristics as compared with resolving MRSA bacteremia (RB). These preliminary data provide a solid foundation to investigate our central hypotheses: early agr activation is an important pathogenic signature in persistent MRSA bacteremia. To test our hypotheses, we will achieve the following integrated Specfic Aims: 1) Define agr RNAIII transcription, functionality and locus sequence profiles in vitro in an expanded collection of well- characterized PB vs. RB strains; and 2) Define agr transcription and functionality in vivo using the experiment IE model, and evaluate the impact of these agr profiles on innate MRSA virulence and antimicrobial efficacy outcomes in the model. Northern blot analyses, gene sequence, nucleic acid sequence-based amplification (NASBA) and quantitative RT-PCR will be employed in this project. These studies will significantly advance our understanding the pathogenesis of MRSA infections. Our long-term goal is to identify unique PB signatures for development of rapid diagnostic means and novel antimicrobial strategies against MRSA infections, such as PB.
描述(由申请方提供):金黄色葡萄球菌是社区获得性和医院感染的主要原因。此外,它是皮肤和皮肤结构感染以及心内膜炎的最常见原因,并且是菌血症的第二常见原因。尽管使用新一代抗生素,但与S。金黄色葡萄球菌感染仍然高得不可接受。持续性MRSA菌血症(PB)是S.金黄色葡萄球菌感染,并与特别严重的结果相关。因此,PB对医学界提出了重大的治疗挑战。了解PB的相关分子机制对优化治疗危及生命的S。金黄色葡萄球菌感染我们的初步数据表明,PB的临床结果与解决MRSA菌血症(RB)的关键致病特征的差异显着相关。这些初步数据为研究我们的中心假设提供了坚实的基础:早期agr激活是持续性MRSA菌血症的重要致病特征。为了检验我们的假设,我们将实现以下综合的特异性目的:1)在充分表征的PB与RB菌株的扩大集合中体外确定agr RNAIII转录、功能性和基因座序列谱;和2)使用实验IE模型在体内定义agr转录和功能,并评估这些agr谱对模型中先天MRSA毒力和抗菌功效结果的影响。本研究将采用北方印迹分析、基因测序、基于核酸序列的扩增(NASBA)和定量RT-PCR。这些研究将大大推进我们对MRSA感染发病机制的理解。我们的长期目标是识别独特的PB特征,以开发针对MRSA感染(例如PB)的快速诊断手段和新型抗菌策略。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The role of Staphylococcal carotenogenesis in resistance to host defense peptides and in vivo virulence in experimental endocarditis model.
葡萄球菌胡萝卜素生成在实验性心内膜炎模型中对宿主防御肽的抵抗和体内毒力中的作用。
  • DOI:
    10.1093/femspd/ftv056
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Xiong,YanQ;Yang,Soo-Jin;Tong,StevenYC;Alvarez,DanyaN;Mishra,NagendraN
  • 通讯作者:
    Mishra,NagendraN
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YAN Q. XIONG其他文献

YAN Q. XIONG的其他文献

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{{ truncateString('YAN Q. XIONG', 18)}}的其他基金

The role of purine biosynthesis and stringent response in persistent MRSA endovascular infections
嘌呤生物合成和严格反应在持续性 MRSA 血管内感染中的作用
  • 批准号:
    10543433
  • 财政年份:
    2019
  • 资助金额:
    $ 20.66万
  • 项目类别:
Bicarbonate-Mediated Enhancement of Beta-Lactam-MRSA Killing: Mechanisms and Clinical Translatability
碳酸氢盐介导的 β-内酰胺-MRSA 杀灭增强:机制和临床可转化性
  • 批准号:
    10626037
  • 财政年份:
    2019
  • 资助金额:
    $ 20.66万
  • 项目类别:
The role of purine biosynthesis and stringent response in persistent MRSA endovascular infections
嘌呤生物合成和严格反应在持续性 MRSA 血管内感染中的作用
  • 批准号:
    10307524
  • 财政年份:
    2019
  • 资助金额:
    $ 20.66万
  • 项目类别:
Early agr Activation is a Key Pathogenic Signature in Persistent MRSA Bacteremia
早期 agr 激活是持续性 MRSA 菌血症的关键致病特征
  • 批准号:
    8224120
  • 财政年份:
    2012
  • 资助金额:
    $ 20.66万
  • 项目类别:

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