Control of ExPEC virulence by small RNAs

小 RNA 控制 ExPEC 毒力

基本信息

  • 批准号:
    8075058
  • 负责人:
  • 金额:
    $ 18.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-06-01 至 2013-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): In order to effectively colonize a host and cause disease, bacterial pathogens must have the means to sense and respond to rapidly changing environmental conditions. The adaptable nature of these microbes is largely attributed to the activation or inhibition of proteins that directly or indirectly modulate gene transcription. However, bacteria also encode many regulatory small RNA (sRNA) molecules that can profoundly affect bacterial responses and virulence potential. Most of these sRNAs act by base pairing with target mRNA transcripts, allowing for the post-transcriptional induction or repression of gene expression. In wild type E. coli strains, including E. coli pathogens that cause disease either within or outside of the gastrointestinal tract, sRNAs are likely key regulators of stress resistance, colonization and persistence, and virulence, but the functional roles of sRNAs within these medically and economically important microbes have received slight attention. Productive interactions between individual sRNAs and target transcripts often require input from the RNA chaperone Hfq. Recently, we found that Hfq is critical to the fitness and virulence potential of extraintestinal pathogenic Escherichia coli (ExPEC). These pathogens cause an array of diseases including, sepsis, neonatal meningitis, and urinary tract infections, the latter of which rank among the most common of infectious diseases. Our findings concerning Hfq implicate sRNAs in ExPEC pathogenesis and provide an impetus for better defining the functionality of these regulatory molecules during infection. The primary objectives of this R21 application are to identify the spectrum and functional attributes of sRNAs that are expressed by ExPEC in response to relevant environmental stresses both in vitro and in vivo during the course of an infection. Results obtained from these studies should enhance our understanding of the how ExPEC manages to colonize host tissues and cause disease in the face of numerous innate defenses, highlighting novel targets for the development of both preventive and therapeutic treatments of ExPEC-induced infections. PUBLIC HEALTH RELEVANCE: Strains of Extraintestinal pathogenic Escherichia coli (ExPEC) cause an array of serious illnesses that affect several million individuals each year, costing billions in health care and time loss at work. We propose that ExPEC utilize small regulatory RNA molecules to adapt to rapidly changing environmental conditions during the course of an infection, enabling these pathogens to better colonize and persist within the host.
描述(由申请人提供):为了有效地定殖宿主并引起疾病,细菌病原体必须具有感知和响应快速变化的环境条件的手段。这些微生物的适应性在很大程度上归因于直接或间接调节基因转录的蛋白质的激活或抑制。然而,细菌也编码许多调节性小RNA(sRNA)分子,其可以深刻地影响细菌反应和毒力潜力。这些sRNA中的大多数通过与靶mRNA转录物的碱基配对起作用,从而允许基因表达的转录后诱导或抑制。野生型E.大肠杆菌菌株,包括E.对于在胃肠道内或外引起疾病的大肠杆菌病原体,sRNA可能是应激抗性、定殖和持久性以及毒力的关键调节因子,但sRNA在这些医学和经济上重要的微生物中的功能作用却很少受到关注。单个sRNA和靶转录物之间的有效相互作用通常需要来自RNA伴侣Hfq的输入。最近,我们发现Hfq对肠外致病性大肠杆菌(ExPEC)的适应性和毒力潜力至关重要。这些病原体引起一系列疾病,包括败血症、新生儿脑膜炎和尿路感染,后者是最常见的感染性疾病。我们关于Hfq的研究结果表明sRNA参与了ExPEC的发病机制,并为更好地定义这些调控分子在感染过程中的功能提供了动力。该R21申请的主要目的是鉴定在感染过程中由ExPEC在体外和体内响应相关环境应激而表达的sRNA的谱和功能属性。从这些研究中获得的结果应该增强我们对ExPEC如何在面对众多先天防御时设法定殖宿主组织并引起疾病的理解,突出了开发预防和治疗ExPEC诱导的感染的新靶点。 公共卫生相关性:肠外致病性大肠杆菌(ExPEC)菌株导致一系列严重疾病,每年影响数百万人,花费数十亿美元的医疗保健和工作时间损失。我们建议ExPEC利用小的调节RNA分子来适应感染过程中快速变化的环境条件,使这些病原体能够更好地在宿主体内定植和持续存在。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

MATTHEW A MULVEY其他文献

MATTHEW A MULVEY的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('MATTHEW A MULVEY', 18)}}的其他基金

Impact of Flagellin Variants and Receptors on the Progression and Outcome of Sepsis
鞭毛蛋白变异体和受体对脓毒症进展和结果的影响
  • 批准号:
    9811363
  • 财政年份:
    2019
  • 资助金额:
    $ 18.62万
  • 项目类别:
Impact of Flagellin Variants and Receptors on the Progression and Outcome of Sepsis
鞭毛蛋白变异体和受体对脓毒症进展和结果的影响
  • 批准号:
    9983099
  • 财政年份:
    2019
  • 资助金额:
    $ 18.62万
  • 项目类别:
Impact of Flagellin Variants and Receptors on the Progression and Outcome of Sepsis
鞭毛蛋白变异体和受体对脓毒症进展和结果的影响
  • 批准号:
    10387952
  • 财政年份:
    2019
  • 资助金额:
    $ 18.62万
  • 项目类别:
Impact of Flagellin Variants and Receptors on the Progression and Outcome of Sepsis
鞭毛蛋白变异体和受体对脓毒症进展和结果的影响
  • 批准号:
    10386796
  • 财政年份:
    2019
  • 资助金额:
    $ 18.62万
  • 项目类别:
Bacterial Invasion and Trafficking within the Bladder
膀胱内的细菌入侵和贩运
  • 批准号:
    8162421
  • 财政年份:
    2011
  • 资助金额:
    $ 18.62万
  • 项目类别:
Bacterial Invasion and Trafficking within the Bladder
膀胱内的细菌入侵和贩运
  • 批准号:
    8259743
  • 财政年份:
    2011
  • 资助金额:
    $ 18.62万
  • 项目类别:
Bacterial Invasion and Trafficking within the Bladder
膀胱内的细菌入侵和贩运
  • 批准号:
    8461904
  • 财政年份:
    2011
  • 资助金额:
    $ 18.62万
  • 项目类别:
Bacterial Invasion and Trafficking within the Bladder
膀胱内的细菌入侵和贩运
  • 批准号:
    8660604
  • 财政年份:
    2011
  • 资助金额:
    $ 18.62万
  • 项目类别:
Deciphering ExPEC Virulence Mechanisms
破译 ExPEC 毒力机制
  • 批准号:
    8119241
  • 财政年份:
    2011
  • 资助金额:
    $ 18.62万
  • 项目类别:
Deciphering ExPEC Virulence Mechanisms
破译 ExPEC 毒力机制
  • 批准号:
    8225132
  • 财政年份:
    2011
  • 资助金额:
    $ 18.62万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 18.62万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了