C. jejuni Cytolethal Distending Toxin Cell Interactions

空肠弯曲菌细胞致死膨胀毒素细胞相互作用

基本信息

  • 批准号:
    6757748
  • 负责人:
  • 金额:
    $ 26.79万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-04-01 至 2006-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Campylobacter jejuni is a food and water borne pathogen responsible for severe inflammatory diarrhea in humans. C. jejuni is a NIAID Category B Priority Pathogen because, in part, of the potential of this pathogen to be used as a biowarfare agent to contaminate food- and water supplies over large geographical areas. It is important to understand the basic biology of C. jejuni pathogenesis, which may lead to novel strategies for circumventing the use of this bacterium as a biowarfare agent. However, the pathogenic mechanisms used by C. jejuni to colonize and cause disease in the host are poorly understood. This application is a collaborative proposal between investigators at the University of Houston and UCLA to study the only known exotoxin secreted by C. jejuni. We will investigate the cellular mechanisms of the C. jejuni cytolethal distending toxin (CDT), which causes cell cycle arrest and eventual death of intoxicated mammalian cells, and has been proposed to assist in remodeling the in vivo environment to facilitate colonization of the intestinal tract. In this R21 application, we will begin to explore the hypothesis that CDT discriminates for and binds to a specific plasma membrane receptor on the surface of sensitive cells as an essential early step during cellular intoxication. In this application, we propose experiments for investigating at the molecular level the interactions of CDT with target cells. In Specific Aim 1, University of Houston researchers will characterize the interactions of CDT with sensitive mammalian cell lines. We will determine the specific and non-specific components as well as the affinity of CDT-receptor interactions. In addition, we will establish many how receptors are present per mammalian cell. Moreover, because CDT is a tri-partite toxin comprising three discrete subunits (CdtA, CdtB, and CdtC), we will establish the contribution of each subunit to binding of the toxin. Finally, we will begin to characterize the nature of the CDT receptor. These experiments will be important for establishing the framework for future experiments to identify the molecular basis for CDT receptor discrimination and binding. In Specific Aim 2, we will identify and characterize mutant cell lines that are resistant to CDT. UCLA researchers will use a genetic approach involving two fundamental phases. In phase 1, cell lines will be mutagenized and screened for a loss of sensitivity to CDT. In phase 2, the loss of sensitivity will be characterized, with the goal being the identification of a cell line that is deficient in binding to CDT. These experiments will be crucial for future work to complement the cell-binding defect, which will identify the putative CDT receptor. Results from this research will provide important information about the mechanism of CDT cellular intoxication, and will provide the basis for future work to develop strategies for blocking the action of CDT as an approach for attenuating C. jejuni pathogenesis.
描述(由申请方提供):空肠弯曲菌是一种食源性和水源性病原体,可引起人类严重炎症性腹泻。C.空肠是NIAID B类优先病原体,部分原因是该病原体有可能用作生物战剂,在大的地理区域内污染食物和水供应。了解C.空肠的发病机制,这可能会导致新的战略,规避使用这种细菌作为生物战剂。然而,C.空肠杆菌在宿主体内定殖并引起疾病的机制还知之甚少。这项应用是休斯顿大学和加州大学洛杉矶分校的研究人员合作提出的,目的是研究唯一已知的由C。空肠。我们将探讨C.空肠细胞致死性膨胀毒素(CDT),其引起细胞周期停滞和中毒哺乳动物细胞的最终死亡,并且已经提出帮助重塑体内环境以促进肠道的定殖。在这个R21应用中,我们将开始探索CDT识别并结合敏感细胞表面上的特异性质膜受体作为细胞中毒过程中必不可少的早期步骤的假设。在此应用中,我们提出了在分子水平上研究CDT与靶细胞相互作用的实验。在具体目标1中,休斯顿大学的研究人员将描述CDT与敏感哺乳动物细胞系的相互作用。我们将确定特异性和非特异性组分以及CDT-受体相互作用的亲和力。此外,我们将建立许多受体是如何存在于每个哺乳动物细胞。此外,由于CDT是包含三个离散亚基(CdtA、CdtB和CdtC)的三方毒素,我们将确定每个亚基对毒素结合的贡献。最后,我们将开始描述CDT受体的性质。这些实验将是重要的建立框架,为未来的实验,以确定CDT受体的歧视和结合的分子基础。在具体目标2中,我们将鉴定和表征对CDT具有抗性的突变细胞系。加州大学洛杉矶分校的研究人员将使用涉及两个基本阶段的遗传方法。在第1阶段,将对细胞系进行诱变并筛选对CDT的敏感性丧失。在第2阶段,将表征灵敏度的丧失,目标是鉴定与CDT结合缺陷的细胞系。这些实验将是至关重要的未来工作,以补充细胞结合缺陷,这将确定假定的CDT受体。本研究的结果将提供有关CDT细胞中毒机制的重要信息,并将为未来开发阻断CDT作用的策略提供基础。空肠发病机制

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 }}

Steven R. Blanke其他文献

Helicobacter pylori VacA, a paradigm for toxin multifunctionality
幽门螺杆菌 VacA,毒素多功能性的范例
  • DOI:
    10.1038/nrmicro1095
  • 发表时间:
    2005-03-10
  • 期刊:
  • 影响因子:
    103.300
  • 作者:
    Timothy L. Cover;Steven R. Blanke
  • 通讯作者:
    Steven R. Blanke
Host cell sensing and restoration of mitochondrial function and metabolism within emHelicobacter pylori/em VacA intoxicated cells
宿主细胞对幽门螺杆菌 VacA 中毒细胞内线粒体功能和代谢的感知与恢复
  • DOI:
    10.1128/mbio.02117-23
  • 发表时间:
    2023-09-22
  • 期刊:
  • 影响因子:
    4.700
  • 作者:
    Ami Y. Seeger;Faisal Zaidi;Sammy Alhayek;Rachel M. Jones;Huzaifa Zohair;Robin L. Holland;Ik-Jung Kim;Steven R. Blanke
  • 通讯作者:
    Steven R. Blanke
A bacterial genotoxin reveals a p53-proteasome-LC3 regulatory axis that drives the suppression of autophagy in cells experiencing sublethal DNA damage
一种细菌基因毒素揭示了一个 p53-蛋白酶体-LC3 调节轴,该轴驱动经历亚致死性 DNA 损伤的细胞中自噬的抑制。
  • DOI:
    10.1016/j.isci.2025.112118
  • 发表时间:
    2025-04-18
  • 期刊:
  • 影响因子:
    4.100
  • 作者:
    D’Feau J. Lieu;Molly K. Crowder;Jordan R. Kryza;Batcha Tamilselvam;Paul J. Kaminski;Ik-Jung Kim;Ying-Xing Li;Eunji Jeong;Michidmaa Enkhbaatar;Henry Chen;Sophia B. Son;Hanlin Mok;Kenneth A. Bradley;Heidi Phillips;Steven R. Blanke
  • 通讯作者:
    Steven R. Blanke

Steven R. Blanke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('Steven R. Blanke', 18)}}的其他基金

Cytolethal Distending Toxin and Intestinal Homeostasis
细胞致死膨胀毒素和肠道稳态
  • 批准号:
    10371246
  • 财政年份:
    2021
  • 资助金额:
    $ 26.79万
  • 项目类别:
Intracellular trafficking of the mitochondrial targeting toxin VacA from Helicobacter pylori
幽门螺杆菌线粒体靶向毒素 VacA 的细胞内运输
  • 批准号:
    9054794
  • 财政年份:
    2015
  • 资助金额:
    $ 26.79万
  • 项目类别:
Bacillus-containing vacuole-mediated interactions of Bacillus anthracis with macrophages
含芽孢杆菌液泡介导的炭疽芽孢杆菌与巨噬细胞的相互作用
  • 批准号:
    8829616
  • 财政年份:
    2015
  • 资助金额:
    $ 26.79万
  • 项目类别:
Intracellular trafficking of the mitochondrial targeting toxin VacA from Helicobacter pylori
幽门螺杆菌线粒体靶向毒素 VacA 的细胞内运输
  • 批准号:
    8873801
  • 财政年份:
    2015
  • 资助金额:
    $ 26.79万
  • 项目类别:
Molecular Mechanisms of the H. pylori Vacuolating Toxin
幽门螺杆菌空泡毒素的分子机制
  • 批准号:
    8136829
  • 财政年份:
    2010
  • 资助金额:
    $ 26.79万
  • 项目类别:
C. jejuni Cytolethal Distending Toxin Cell Interactions
空肠弯曲菌细胞致死膨胀毒素细胞相互作用
  • 批准号:
    7133491
  • 财政年份:
    2004
  • 资助金额:
    $ 26.79万
  • 项目类别:
C. jejuni Cytolethal Distending Toxin Cell Interactions
空肠弯曲菌细胞致死膨胀毒素细胞相互作用
  • 批准号:
    6879065
  • 财政年份:
    2004
  • 资助金额:
    $ 26.79万
  • 项目类别:
Blocking Cellular Intoxication by Bacterial Toxins
阻止细菌毒素引起的细胞中毒
  • 批准号:
    6561325
  • 财政年份:
    2002
  • 资助金额:
    $ 26.79万
  • 项目类别:
Blocking Cellular Intoxication by Bacterial Toxins
阻止细菌毒素引起的细胞中毒
  • 批准号:
    6653079
  • 财政年份:
    2002
  • 资助金额:
    $ 26.79万
  • 项目类别:
Molecular Mechanisms of the H. pylori Vacuolating Toxin
幽门螺杆菌空泡毒素的分子机制
  • 批准号:
    8337881
  • 财政年份:
    2000
  • 资助金额:
    $ 26.79万
  • 项目类别:

相似海外基金

CampylobacterでのDNAメチル化による水平伝播制御とエピジェネティクスの解明
弯曲杆菌 DNA 甲基化水平传输控制和表观遗传学的阐明
  • 批准号:
    24K10219
  • 财政年份:
    2024
  • 资助金额:
    $ 26.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
生菌のCampylobacterはCDTをどのように菌体外へと分泌し作用させているのか?
活的弯曲杆菌如何将CDT分泌到细胞外并使其发挥作用?
  • 批准号:
    24K18439
  • 财政年份:
    2024
  • 资助金额:
    $ 26.79万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Structural and functional characterization of glycosyltransferases in the Campylobacter concisus N-linked glycoconjugate biosynthetic pathway
弯曲杆菌 N 连接糖复合物生物合成途径中糖基转移酶的结构和功能表征
  • 批准号:
    10607139
  • 财政年份:
    2023
  • 资助金额:
    $ 26.79万
  • 项目类别:
BBSRC United States Partnering Award: Advancement of (meta) genomic tools to study the transmission of Campylobacter and other low abundance pathogens
BBSRC 美国合作奖:研究弯曲杆菌和其他低丰度病原体传播的(元)基因组工具的进步
  • 批准号:
    BB/X018482/1
  • 财政年份:
    2023
  • 资助金额:
    $ 26.79万
  • 项目类别:
    Research Grant
Campylobacter jejuni restriction by the intestinal microbiota
空肠弯曲菌受肠道微生物群的限制
  • 批准号:
    10734573
  • 财政年份:
    2023
  • 资助金额:
    $ 26.79万
  • 项目类别:
Campylobacter pathogenesis: the Unfolded Protein Response (UPR), inflammation and human disease
弯曲杆菌发病机制:未折叠蛋白反应 (UPR)、炎症和人类疾病
  • 批准号:
    2881697
  • 财政年份:
    2023
  • 资助金额:
    $ 26.79万
  • 项目类别:
    Studentship
Formation and resuscitation of viable but non-culturable Campylobacter in agri-food industry
农业食品工业中活的但不可培养的弯曲杆菌的形成和复苏
  • 批准号:
    RGPIN-2019-03960
  • 财政年份:
    2022
  • 资助金额:
    $ 26.79万
  • 项目类别:
    Discovery Grants Program - Individual
Protein phosphorylation and Campylobacter jejuni pathogenesis
蛋白质磷酸化和空肠弯曲菌发病机制
  • 批准号:
    10608212
  • 财政年份:
    2022
  • 资助金额:
    $ 26.79万
  • 项目类别:
Genomic Epidemiology and Transmission of Campylobacter in Africa (GETcampy-Africa)
非洲弯曲杆菌的基因组流行病学和传播 (GETcampy-Africa)
  • 批准号:
    MR/V001213/2
  • 财政年份:
    2022
  • 资助金额:
    $ 26.79万
  • 项目类别:
    Research Grant
Exploring aspects of helical shape biogenesis in Campylobacter jejuni
探索空肠弯曲杆菌螺旋形状生物发生的各个方面
  • 批准号:
    574337-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 26.79万
  • 项目类别:
    University Undergraduate Student Research Awards
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了