The function of the essential Helicobacter pylori virulence factor gamma-glutamyltranspeptidase for gastric colonization and immune response in vivo
幽门螺杆菌必需毒力因子γ-谷氨酰转肽酶在胃定植和体内免疫反应中的功能
基本信息
- 批准号:393101970
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2018
- 资助国家:德国
- 起止时间:2017-12-31 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Infection with Helicobacter pylori (H. pylori) is an extremely common condition, as it affects half of the world population. This persistent infection causes gastric inflammation and more severe gastric pathology that in some cases even culminates in gastric cancer. Several virulence factors determine the clinical outcome. Of those, H. pylori gamma-glutamyltransferase (HpgGT) has emerged as an essential virulence factor whose activity is associated with severity of gastric disease in infected individuals. This periplasmic enzyme catalyzes hydrolysis of gamma-glutamyl compounds, such as glutamine and glutathione. Effects of HpgGT on bacteria, isolated host cells and cell lines have revealed several possible modes of action, such as support of bacterial metabolism and acid resistance, induction of oxidative stress, glutamine deprivation and production of toxic ammonia. However, the specific function of this enzyme at different stages of infection in vivo as well as how it influences colonization and gastric inflammation remain unclear. Therefore, we propose to elucidate gGT-dependent effects using H. pylori PMSS1 wild type and its isogenic gGT-deficient strain in a mouse model of infection. Our preliminary data indicate a dual role of HpgGT in supporting bacterial metabolism and in affecting the gastric immune response during persistent colonization; however, further analyses are necessary to clarify the underlying molecular and cellular mechanisms. Taken together, this study will not only contribute to the understanding of H. pylori infection and of the gastric pathology, but might also prepare the ground for the development of novel therapeutic approaches.
幽门螺杆菌感染是一种极其常见的疾病,因为它影响了世界上一半的人口。这种持续的感染引起胃炎症和更严重的胃病理,在某些情况下甚至最终导致胃癌。几个毒力因素决定了临床结果。其中,幽门螺杆菌γ -谷氨酰转移酶(HpgGT)已成为一种重要的毒力因子,其活性与感染个体的胃病严重程度有关。这种质周酶催化γ -谷氨酰基化合物的水解,如谷氨酰胺和谷胱甘肽。HpgGT对细菌、分离宿主细胞和细胞系的影响揭示了几种可能的作用模式,如支持细菌代谢和耐酸性、诱导氧化应激、谷氨酰胺剥夺和产生有毒氨。然而,该酶在体内不同感染阶段的具体功能以及它如何影响定植和胃炎症尚不清楚。因此,我们建议在小鼠感染模型中使用幽门螺杆菌PMSS1野生型及其等基因ggt缺陷菌株来阐明ggt依赖性作用。我们的初步数据表明,在持续定植过程中,HpgGT在支持细菌代谢和影响胃免疫反应方面具有双重作用;然而,需要进一步的分析来阐明潜在的分子和细胞机制。综上所述,本研究不仅有助于了解幽门螺杆菌感染和胃病理,而且可能为开发新的治疗方法奠定基础。
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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Professor Dr. Markus Gerhard其他文献
Professor Dr. Markus Gerhard的其他文献
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{{ truncateString('Professor Dr. Markus Gerhard', 18)}}的其他基金
Identification and validation of H. pylori-associated gastric cancer biomarkers in Chinese and German populations
中国和德国人群中幽门螺杆菌相关胃癌生物标志物的鉴定和验证
- 批准号:
410192478 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Research Grants
The stem cell ubiquitin ligase RNF43 in gastric homeostasis, DNA damage response and carcinogenesis: from biological function to application as biomarker
干细胞泛素连接酶 RNF43 在胃稳态、DNA 损伤反应和致癌作用中的作用:从生物学功能到作为生物标志物的应用
- 批准号:
396415377 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Research Grants
Employment of CEA-related cell adhesion molecules (CEACAMs) by Helicobacter pylori
幽门螺杆菌利用 CEA 相关细胞粘附分子 (CEACAM)
- 批准号:
308500591 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Grants
Activation of alternative NF-kB signaling in the stomach: link to H. pylori virulence factors and effect on gastric inflammation and gastric pathogenesis
胃中替代 NF-kB 信号的激活:与幽门螺杆菌毒力因子的联系以及对胃炎症和胃发病机制的影响
- 批准号:
312925791 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Grants
Analyse der Rolle von Zielgenen des Wnt Signalweges in der Entwicklung und Tumorentstehung
Wnt信号通路靶基因在发育和肿瘤发生中的作用分析
- 批准号:
94717299 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Research Grants
Structural and functional consequences of the CEACAM-HopQ mediated binding of Helicobacter pylori to human gastric epithelial cells in vitro and in vivo
CEACAM-HopQ 介导幽门螺杆菌与人胃上皮细胞体外和体内结合的结构和功能后果
- 批准号:
465689316 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
相似国自然基金
DDAH/ADMA/NOS系统基因多态性与原发性高血压易感性及其机制研究
- 批准号:30671149
- 批准年份:2006
- 资助金额:28.0 万元
- 项目类别:面上项目
相似海外基金
Acid Adaptation Targets for Eradication of Helicobacter pylori
根除幽门螺杆菌的酸适应目标
- 批准号:
9486844 - 财政年份:2010
- 资助金额:
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Acid Adaptation Targets for Eradication of Helicobacter pylori
根除幽门螺杆菌的酸适应目标
- 批准号:
8817059 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Acid Adaptation Targets for Eradication of Helicobacter pylori
根除幽门螺杆菌的酸适应目标
- 批准号:
9275334 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Helicobacter Pylori and its Presence and its Role in the Formation of Diseases of the Gastrointestinal Tract of Humans.
幽门螺杆菌及其存在及其在人类胃肠道疾病形成中的作用。
- 批准号:
184102 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Studentship Programs
Essential role of MD-2 in TLR4-dependent signaling during Helicobacter pylori- associated gastritis
MD-2 在幽门螺杆菌相关性胃炎期间 TLR4 依赖性信号传导中的重要作用
- 批准号:
15590647 - 财政年份:2003
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of complementary and alternative medicine against antibiotic-resistant Helicobacter pylori infection
针对抗生素耐药性幽门螺杆菌感染的补充和替代医学的发展
- 批准号:
15590602 - 财政年份:2003
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)