Host and Bacterial Factors in Disease due to H. pylori
幽门螺杆菌疾病的宿主和细菌因素
基本信息
- 批准号:7066068
- 负责人:
- 金额:$ 27.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-05-01 至 2008-04-30
- 项目状态:已结题
- 来源:
- 关键词:Helicobacterantigen presenting cellantigen receptorsbacteria infection mechanismbacterial antigensbacterial cytopathogenic effectbacterial proteinsgastritisgenetic mappinggenetic promoter elementgenetic regulationhost organism interactioninfectionlaboratory mouselipopolysaccharidesmolecular cloningnucleic acid sequenceprotein localizationprotein structure functionvirulence
项目摘要
DESCRIPTION (provided by applicant): H. pylori has been called the most common infectious disease of humans in the world today. Worldwide, between 50-100% of people are infected with H. pylori, but only a minority of those develop clinical signs of disease. Almost 2 decades of research have resulted in a general consensus that both host and bacterial factors contribute to disease, but the specific bacterial factors involved and the mechanisms whereby they promote colonization and induce severe manifestations of disease are not well understood. The overall goal of this project is to investigate these mechanisms. In the first funding interval we developed a mouse model of severe disease in which the contributions of host and bacterial factors to severe manifestations of disease can be evaluated. We utilized this model to determine the T cell subsets and cytokines that contribute to disease, we identified one bacterial factor, lipopolysaccharide O-antigen, that induces a deleterious host response and thus contributes to the outcome of disease, and we identified an H. pylori promoter, cagl5, that is upregulated in vivo and likely represents a new virulence factor. In this renewal, we will investigate the roles of O-antigen and cagl 5 in H. pylori pathogenesis, and use a newly-developed promoter trap to identify H. pylori genes that are upregulated in vivo. The 3 specific aims are:
Specific aim 1: To test the hypothesis that cag15 has a role in survival of H. pylori in vivo, and to determine the role of the cagl5 gene product in colonization and disease.
Specific aim 2: To use a ureB reporter construct for promoter trapping, to identify novel colonization factors that are induced by growth in vivo, and to test the hypothesis that upregulated genes are essential for or facilitate colonization by and/or gastritis due to H. pylori.
Specific aim 3: To test the hypothesis that the polysaccharide moiety of H. pylori lipopolysaccharide induces gastritis by receptor-mediated activation of antigen presenting cells. Successful completion of these aims will lead to improved understanding of the pathogenesis of H. pylori associated disease and provide a foundation for development of novel therapies.
描述(由申请人提供):幽门螺旋杆菌被称为当今世界上人类最常见的传染病。在世界范围内,50% -100%的人感染了幽门螺杆菌,但其中只有少数人出现了疾病的临床症状。近20年的研究已经形成了一个普遍的共识,即宿主和细菌因素都有助于疾病,但具体涉及的细菌因素及其促进定植和诱发严重疾病表现的机制尚不清楚。这个项目的总体目标是研究这些机制。在第一个资助期,我们开发了一种严重疾病的小鼠模型,可以评估宿主和细菌因素对疾病严重表现的贡献。我们利用这个模型来确定导致疾病的T细胞亚群和细胞因子,我们发现了一种细菌因子,脂多糖o抗原,它会诱导有害的宿主反应,从而导致疾病的结果,我们发现了一种幽门螺杆菌启动子,cagl5,它在体内上调,可能代表一种新的毒力因子。在本次更新中,我们将研究o抗原和cagl5在幽门螺杆菌发病中的作用,并使用新开发的启动子陷阱来鉴定体内上调的幽门螺杆菌基因。这三个具体目标是:
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)
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KATHRYN A. EATON其他文献
KATHRYN A. EATON的其他文献
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{{ truncateString('KATHRYN A. EATON', 18)}}的其他基金
The role of prophage life cycle in Stx production and disease due to EHEC
原噬菌体生命周期在 Stx 产生和 EHEC 引起的疾病中的作用
- 批准号:
8416401 - 财政年份:2012
- 资助金额:
$ 27.25万 - 项目类别:
The role of prophage life cycle in Stx production and disease due to EHEC
原噬菌体生命周期在 Stx 产生和 EHEC 引起的疾病中的作用
- 批准号:
8243170 - 财政年份:2012
- 资助金额:
$ 27.25万 - 项目类别:
Recombinant murine IL-10 produced in situ by H. pylori
由幽门螺杆菌原位产生的重组鼠 IL-10
- 批准号:
6833463 - 财政年份:2003
- 资助金额:
$ 27.25万 - 项目类别:
Recombinant murine IL-10 produced in situ by H. pylori
由幽门螺杆菌原位产生的重组鼠 IL-10
- 批准号:
6709130 - 财政年份:2003
- 资助金额:
$ 27.25万 - 项目类别:
Host and Bacterial Factors in Disease due to H. Pylori
幽门螺杆菌疾病的宿主和细菌因素
- 批准号:
7730235 - 财政年份:1998
- 资助金额:
$ 27.25万 - 项目类别:
Host and Bacterial Factors in Disease due to H. pylori
幽门螺杆菌疾病的宿主和细菌因素
- 批准号:
7231007 - 财政年份:1998
- 资助金额:
$ 27.25万 - 项目类别:
HOST AND BACTERIAL FACTORS IN DISEASE DUE TO H PYLORI
幽门螺杆菌引起的疾病的宿主和细菌因素
- 批准号:
2887829 - 财政年份:1998
- 资助金额:
$ 27.25万 - 项目类别:
Host and Bacterial Factors in Disease due to H. pylori
幽门螺杆菌疾病的宿主和细菌因素
- 批准号:
6731771 - 财政年份:1998
- 资助金额:
$ 27.25万 - 项目类别:
HOST AND BACTERIAL FACTORS IN DISEASE DUE TO H PYLORI
幽门螺杆菌引起的疾病的宿主和细菌因素
- 批准号:
2689786 - 财政年份:1998
- 资助金额:
$ 27.25万 - 项目类别:
HOST AND BACTERIAL FACTORS IN DISEASE DUE TO H PYLORI
幽门螺杆菌引起的疾病的宿主和细菌因素
- 批准号:
6171006 - 财政年份:1998
- 资助金额:
$ 27.25万 - 项目类别:
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