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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.

细菌病原体已经进化出多种策略来定殖多细胞生物并抵消或规避宿主的防御机制。目前，毒素、粘附素、铁螯合剂或免疫调节剂等蛋白质是最了解的效应物，微生物利用它们来靶向宿主中的特定过程。我们之前研究了一组特定的细菌粘附素，它们介导几种与人类相关的微生物与粘膜表面的紧密附着。与宿主细胞结合后，这些病原体抑制表面上皮细胞的脱落，从而促进这些微生物在粘膜表面的定植。我们现在已经获得初步证据，表明细菌粘附素是亲密附着的先决条件，但它是病原体释放的气体（NO；一氧化氮），最终触发观察到的宿主细胞反应。该提议旨在澄清微生物释放的 NO 是否确实是调节剥脱和粘膜定植的关键决定因素。 NO 的这种分子串扰代表了原核生物与其宿主之间的一种新的通讯模式。此外，由于一氧化氮诱导的过程易于药物干预，因此我们的研究结果可能会开辟预防或阻止传染病的全新途径。