Functional characterization of the pH-sensing ArsRS two-component system of Helicobacter pylori and of its regulon

幽门螺杆菌 pH 传感 ArsRS 双组分系统及其调节子的功能表征

• 批准号: 20067104
• 负责人: Professorin Dr. Dagmar Beier
• 金额: --
• 依托单位: Lehrstuhl für Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/20067104?language=en
• 关键词: Functional; characterization; pH; sensing; ArsRS

The human gastric pathogen Helicobacter pylori is the causative agent of chronic type B gastritis and gastric or duodenal ulcer disease. Moreover, infection with H. pylori is known to be associated with the development of gastric adenocarcinoma and MALT lymphoma. The ability of the neutralophilic bacterium H. pylori to cope with the extremely acidic pH of the stomach lumen is indispensable for the successful colonization of its niche. pH-dependent gene regulation including the control of expression of the essential colonization factor urease is mediated by the ArsRS two-component system via a phosphorelay which is triggered by low pH. However, the observation that arsR is an essential gene, while arsS is not, indicates that additional target genes exist which are not pH-regulated but require the unphosphorylated response regulator ArsR for their transcriptional control. The aim of the present proposal is the characterization of the ArsRS acid response system and the role of unphosphorylated ArsR by the identification of the complete ArsR-dependent regulon. Furthermore, the mechanism of pH-sensing by the periplasmic input domain of the histidine kinase ArsS will be investigated in detail and a functional comparison with the orthologous sensor proteins of related non-gastric members of the ¿-proteobacteria will be performed.

幽门螺杆菌是引起慢性B型胃炎、胃溃疡和十二指肠溃疡的主要病原菌。此外，H.已知幽门螺杆菌与胃腺癌和MALT淋巴瘤的发生有关。嗜中性细菌H.幽门螺杆菌以科普胃腔的极酸性pH对于其生态位的成功定植是必不可少的。pH依赖性基因调控，包括控制的基本定植因子尿素酶的表达介导的ArsRS双组分系统通过磷酸化，这是由低pH值触发。然而，观察arsR是一个必需的基因，而arsS不是，表明存在额外的靶基因，这不是pH值调节，但需要非磷酸化的反应调节剂ArsR的转录控制。本提案的目的是表征的ArsRS酸反应系统和未磷酸化的ArsR的作用，通过鉴定完整的ArsR依赖性调节子。此外，组氨酸激酶ArsS的周质输入结构域的pH传感的机制将进行详细研究，并与相关的非胃的成员的邻位传感器蛋白质的功能比较将进行？-变形菌。