In vivo Reporters of Mycobacterium tuberculosis ESX-5 Secretion

结核分枝杆菌 ESX-5 分泌的体内报告基因

基本信息

  • 批准号:
    10372365
  • 负责人:
  • 金额:
    $ 23.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-22 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Mycobacterium tuberculosis (Mtb) requires the specialized Type VII protein secretion system ESX-5 for growth in vitro, but little is known about the expression or activity of ESX-5 during infection. A recent report suggested ESX-5 genes are transcriptionally induced at the acute stage of infection in mice. However, the regulatory networks and host signals that stimulate ESX-5 expression as well as the stage(s) of infection at which ESX-5 is induced remain to be comprehensively identified. The overall objective of this proposal is to characterize how Mtb regulates ESX-5 secretion during infection. The proposed research will test the central hypothesis that ESX-5 is activated in response to specific nutritional cues or environmental stressors to counteract growth restriction in host interstitial macrophages. Prior studies implicated phosphate limitation as one signal that induces ESX-5 activity in vitro, but disrupting phosphate-dependent ESX-5 regulation did not impact Mtb growth or persistence in mice, suggesting that other uncharacterized regulators control ESX-5 in the host. Preliminary data show that over-expression of two different transcriptional regulators can induce ESX-5 secretion in vitro. Specific Aim 1 will test the hypothesis that specific transcription factors activate ESX-5 in response to nutritional cues and stress conditions that Mtb encounters in host macrophages. In Specific Aim 2, fluorescent ESX-5 transcriptional reporters will be developed and tested in macrophage and mouse infection models using flow cytometry to determine when and in what cell types ESX-5 expression is induced during infection. Fluorescent reporters of ESX-5 substrate export will also be developed for analysis of ESX-5 activity during macrophage infection. The innovative fluorescent reporters developed will enable future screens for small molecules that disrupt ESX-5 expression and/or activity. The proposed research is significant because it will fill important gaps in knowledge of ESX-5 function by identifying the host cues and regulatory factors that control ESX-5 expression and establishing the stage(s) of infection when Mtb will be most vulnerable to drugs targeting ESX-5 or its regulation.
项目总结/摘要 结核分枝杆菌(Mtb)需要专门的VII型蛋白分泌系统ESX-5进行生长 在体外,但对ESX-5在感染过程中的表达或活性知之甚少。最近的一份报告显示, ESX-5基因在小鼠感染的急性期被转录诱导。但监管 刺激ESX-5表达的网络和宿主信号以及感染阶段, 仍有待全面查明。本提案的总体目标是描述 Mtb如何在感染期间调节ESX-5分泌。拟议中的研究将检验中心假设 ESX-5在特定的营养提示或环境压力下被激活,以抵消生长 限制宿主间质巨噬细胞。先前的研究暗示磷酸盐限制是一个信号, 体外诱导ESX-5活性,但破坏磷酸盐依赖性ESX-5调节并不影响Mtb 在小鼠中的生长或持久性,表明其他未表征的调节剂控制宿主中的ESX-5。 初步数据显示,两种不同转录调控因子的过表达可以诱导ESX-5 体外分泌。Specific Aim 1将检验特异性转录因子激活ESX-5的假设, Mtb在宿主巨噬细胞中遇到的营养提示和应激条件的反应。在具体目标2中, 荧光ESX-5转录报告基因将在巨噬细胞和小鼠感染中开发和测试 模型使用流式细胞术来确定何时以及在何种细胞类型中诱导ESX-5表达, 感染还将开发ESX-5底物输出的荧光报告物,用于分析ESX-5活性 在巨噬细胞感染期间。开发的创新荧光记者将使未来的屏幕能够 破坏ESX-5表达和/或活性的小分子。这项研究意义重大,因为它 将通过识别主机提示和调节因素, 控制ESX-5的表达,并确定结核分枝杆菌最易受药物影响的感染阶段 针对ESX-5或其监管。

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 }}

Anna DeGraff Tischler其他文献

Anna DeGraff Tischler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('Anna DeGraff Tischler', 18)}}的其他基金

PPE Export by the Essential ESX-5 Secretion System in M. tuberculosis Virulence
结核分枝杆菌毒力中基本 ESX-5 分泌系统的 PPE 输出
  • 批准号:
    10439881
  • 财政年份:
    2021
  • 资助金额:
    $ 23.25万
  • 项目类别:
PPE Export by the Essential ESX-5 Secretion System in M. tuberculosis Virulence
结核分枝杆菌毒力中基本 ESX-5 分泌系统的 PPE 输出
  • 批准号:
    10286476
  • 财政年份:
    2021
  • 资助金额:
    $ 23.25万
  • 项目类别:
In vivo Reporters of Mycobacterium tuberculosis ESX-5 Secretion
结核分枝杆菌 ESX-5 分泌的体内报告基因
  • 批准号:
    10493351
  • 财政年份:
    2021
  • 资助金额:
    $ 23.25万
  • 项目类别:
Redefining Mycobacterium tuberculosis genes essential for infection
重新定义感染所必需的结核分枝杆菌基因
  • 批准号:
    9977614
  • 财政年份:
    2020
  • 资助金额:
    $ 23.25万
  • 项目类别:
High-Throughput Identification of Mycobacterium tuberculosis Persistence Mechanis
结核分枝杆菌持续机制的高通量鉴定
  • 批准号:
    8566012
  • 财政年份:
    2013
  • 资助金额:
    $ 23.25万
  • 项目类别:

相似海外基金

AEROSOLS
气雾剂
  • 批准号:
    10101317
  • 财政年份:
    2024
  • 资助金额:
    $ 23.25万
  • 项目类别:
    EU-Funded
AEROSOLS - AIR QUALITY AND HEALTH IMPACT OF PRIMARY SEMI-VOLATILE AND SECONDARY PARTICLES AND THEIR ABATEMENT
气溶胶 - 一次半挥发性颗粒和二次颗粒对空气质量和健康的影响及其消除
  • 批准号:
    10092043
  • 财政年份:
    2024
  • 资助金额:
    $ 23.25万
  • 项目类别:
    EU-Funded
Molecular-level Understanding Of Atmospheric Aerosols (MUOAA 2024); Corsica, France; April 1-5, 2024
对大气气溶胶的分子水平理解(MUOAA 2024);
  • 批准号:
    2332007
  • 财政年份:
    2024
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Standard Grant
TWISTA (The Wide-ranging Impacts of STratospheric smoke Aerosols)
TWISTA(平流层烟雾气溶胶的广泛影响)
  • 批准号:
    NE/Y000021/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Research Grant
TWISTA (The Wide-ranging Impacts of STratospheric smoke Aerosols)
TWISTA(平流层烟雾气溶胶的广泛影响)
  • 批准号:
    NE/Y000358/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Research Grant
Southern Ocean aerosols: sources, sinks and impact on cloud properties
南大洋气溶胶:来源、汇以及对云特性的影响
  • 批准号:
    DP240100389
  • 财政年份:
    2024
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Discovery Projects
An AI-driven clinical washbasin unit that automatically disinfects pathogens, reduces aerosols and decreases healthcare-acquired infections by 70%
%20人工智能驱动%20临床%20洗脸盆%20单位%20%20自动%20消毒%20病原体,%20减少%20气溶胶%20和%20减少%20医疗保健获得性%20感染%20by%2070%
  • 批准号:
    83001507
  • 财政年份:
    2023
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Innovation Loans
Cloudbusting with JWST: characterising aerosols, aurorae and chemistry in substellar atmospheresto the water cloud regime
使用 JWST 进行云消除:描述水云状态下恒星大气中的气溶胶、极光和化学成分
  • 批准号:
    ST/X001091/1
  • 财政年份:
    2023
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Research Grant
INvestigating Home water and Aerosols' Links to opportunistic pathogen Exposure (INHALE): do consumer decisions impact pathogen exposure and virulence?
调查家庭用水和气溶胶与机会性病原体暴露(吸入)的联系:消费者的决定是否会影响病原体暴露和毒力?
  • 批准号:
    2326096
  • 财政年份:
    2023
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Standard Grant
Bioactivated Aerosols for Combustion Product Capture
用于燃烧产物捕获的生物活性气溶胶
  • 批准号:
    10080253
  • 财政年份:
    2023
  • 资助金额:
    $ 23.25万
  • 项目类别:
    Small Business Research Initiative
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了