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Signaling via LuxR solos in the insect pathogen Photorhabdus luminescens and the human pathogen Photorhabdus asymbiotica

昆虫病原体发光杆菌和人类病原体非共生发光杆菌中通过 LuxR alones 发出的信号

基本信息

批准号：
190135878
负责人：
Professor Dr. Ralf Heermann
金额：
--
依托单位：
Institut für Molekulare Physiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/190135878?language=en
关键词：
Signaling via LuxR solos insect

项目摘要

It is well recognised that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those that use acylated homoserine lactones (AHLs) for communication. The prototype of those systems consists of a LuxI-like AHL synthase and a cognate LuxR-receptor that senses the signal. However, many proteobacteria possess LuxR receptors yet lack any LuxI-type synthase, and thus these receptors are referred to as LuxR orphans or solos. Photorhabdus luminescens is an insect pathogenic bacterium that has a total of 39 LuxR solos, which is one of the highest numbers that has ever been found in bacteria. In the previous funding period we found that one of these LuxR solos, PluR, is part of a novel cell-cell communication system. Instead of AHLs, PluR senses alpha-pyrones, named photopyrones (PPYs), produced by the pyrone synthase PpyS as signaling molecules. PluR was the first example of a LuxR solo that senses a quorum sensing signal that is not an AHL. The closely related insect and human pathogen Photorhabdus asymbiotica has a close homologue to PluR, named PauR, but lacks LuxI as well as PpyS homologues. We have first evidence that PauR senses dialkylresorcinols (DARs) and their precursors cyclohexanediones (CHDs) instead of PPYs and AHLs as signal. In this project we will therefore investigate this novel DAR/CHD-based cell-cell communication system in the native host P. asymbiotica. Moreover, we will attempt to identify amino acid motifs in the signal-binding domain of PluR and PauR that make them specific PPY or DAR/CHD sensors, respectively, and that distinguish them from the AHL sensors. Additionally, we will investigate the DNA-binding site(s) of PluR and PauR to define a specific DNA-binding box of these LuxR solos. Besides LuxR solos that contain a putative AHL binding domain, the majority of the LuxR solos in P. luminescens have a PAS4 domain. We know that the PAS4-LuxR solo Plu2018/Plu2019 is part of a novel type of inter-kingdom signaling system, as the signal is present in the insect Galleria mellonella. We therefore aim to identify the chemical nature of this inter-kingdom signal in the current project proposal. As all the LuxR solos that are investigated in this project are involved in pathogenicity and have homologues in diverse human pathogenic bacteria, they might act as targets for novel antimicrobials in the future.

众所周知，细菌通过可扩散的小分子进行交流，这一过程被称为群体感应。最容易理解的群体感应系统是那些使用酰基化同丝氨酸内酯（ahl）进行通信的系统。这些系统的原型由一个类似luxxi的AHL合成酶和一个同源的luxr受体组成。然而，许多变形菌具有LuxR受体，但缺乏任何luxi型合酶，因此这些受体被称为LuxR孤儿或孤独者。光habdus luminescens是一种昆虫致病菌，共有39个LuxR单链，这是迄今为止在细菌中发现的数量最多的细菌之一。在之前的资助期内，我们发现其中一个LuxR单链，PluR，是一种新型细胞-细胞通信系统的一部分。与ahl不同，PluR感知由pyro酮合成酶PPYs产生的α - pyro酮，称为光丙酮（PPYs）作为信号分子。PluR是LuxR独奏器的第一个例子，它可以感知非AHL的quorum sensing信号。与昆虫和人类密切相关的病原菌无共生光habdus asymbiotica与PluR有密切的同源性，命名为PauR，但缺乏LuxI和PpyS的同源性。我们首次获得了PauR感知二烷基间苯二酚（dar）及其前体环己二酮（CHDs）而不是PPYs和ahl作为信号的证据。因此，在本项目中，我们将研究这种基于DAR/ chd的新型细胞-细胞通信系统在原生寄主P. asymbiotica中的作用。此外，我们将尝试在PluR和PauR的信号结合域中识别氨基酸基序，这些氨基酸基序分别使它们成为特定的PPY或DAR/CHD传感器，并将它们与AHL传感器区分开来。此外，我们将研究PluR和PauR的dna结合位点，以确定这些LuxR solo的特定dna结合盒。除了LuxR单链含有一个假定的AHL结合结构域外，P. luminescens中的大多数LuxR单链都有一个PAS4结构域。我们知道PAS4-LuxR独奏Plu2018/Plu2019是一种新型王国间信号系统的一部分，因为该信号存在于昆虫mellonella中。因此，我们的目标是在当前的项目提案中确定这种王国间信号的化学性质。由于本项目研究的所有LuxR单克隆体都涉及致病性，并且在多种人类致病菌中具有同源物，因此它们可能成为未来新型抗菌药物的靶点。