Regulation of host tissue responses by pathogen-derived nitric oxide (NO)

病原体来源的一氧化氮 (NO) 调节宿主组织反应

基本信息

批准号：
393235587
负责人：
Professor Dr. Christof Robert Hauck
金额：
--
依托单位：
Lehrstuhl Zellbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/393235587?language=en
关键词：
Regulation host tissue responses pathogen

项目摘要

Bacterial pathogens have evolved numerous strategies to colonize multicellular organisms and to counteract or circumvent defense mechanisms of their hosts. Currently, proteins such as toxins, adhesins, iron chelators or immunomodulators are the best understood effectors, which are employed by microbes to target particular processes in their host.We have previously investigated a group of specific bacterial adhesins, which mediate tight attachment of several human-associated microorganism to the surface of the mucosa. Upon host cell binding, these pathogens suppress the exfoliation of superficial epithelial cells, thereby promoting the colonization of the mucosal surface by these microbes. We have now obtained preliminary evidence that the bacterial adhesins constitute a pre-requisite for the intimate attachment, but that it is a gas released by the pathogens (NO; nitric oxid), which ultimately triggers the observed host cell responses. This proposal is set to clarify, if NO release by microorganisms is indeed the critical determinant modulating exfoliation and mucosal colonization. Such a molecular cross-talk by NO would represent a novel mode of communication between prokaryotes and their host. Moreover, as NO-induced processes are amenable to pharmacological intervention, the results of our investigation could open up completely novel avenues to prevent or block infectious diseases.

细菌病原体已经发展了许多策略，以定居多细胞生物并抵消其宿主的防御机制。当前，诸如毒素，粘附素，铁螯合剂或免疫调节剂之类的蛋白质是最有理理解的效应子，由微生物使用它们来靶向其宿主中的特定过程。我们先前已经研究了一组特定的细菌粘附素，它们介导了几种与人类相关的微生物与穆学习蛋白相关的紧密连接。宿主细胞结合后，这些病原体抑制了表面上皮细胞的去角质，从而促进了这些微生物对粘膜表面的定殖。现在，我们已经获得了初步证据，表明细菌粘附素构成了亲密附着的先决条件，但它是病原体释放的气体（NO；一氧化氧化），最终触发了观察到的宿主细胞反应。如果没有微生物的释放确实是调节剥落和粘膜定殖的关键决定因素，则该提议将澄清。这样的分子串扰将代表原核生物与宿主之间的新型交流方式。此外，由于无诱导的过程适合药理学干预，因此我们研究的结果可能会打开完全新颖的途径，以预防或阻止传染病。