Molecular analysis of gene regulators in the remarkable iron-ome of the symbiotic bacterium Rhizobium.

共生细菌根瘤菌的显着铁组中基因调节因子的分子分析。

基本信息

批准号：
BB/E003400/1
负责人：
Andrew Johnston
金额：
$ 53.99万
依托单位：
University of East Anglia
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FE003400%2F1
关键词：
Molecular analysis gene regulators remarkable

项目摘要

Iron may or not be in the soul, but it is certainly in the soma, as a major player in the functioning of all living cells. It is needed to transport oxygen in the blood, to help us cope with many different toxins and for a thousand and one other essential biochemical functions. This is because iron has special chemical properties that can drive all sorts of oxidation and other energy-generating steps, and so it occurs in many enzymes that catalyse these sorts of reactions. However, an excess of iron within cells can be very harmful, since its same 'redox' properties can also generate some very nasty substances. These so-called 'radicals' can damage the DNA, the lipids and the proteins in the cells. It is therefore crucial that living things control their amounts of iron to just the right level. We are studying how this so-called 'homeostasis' is achieved in a bacterium called Rhizobium, whose main claim to fame is that it forms nitrogen-fixing nodules on the roots of legume plants. These include many familiar crops, such as peas, beans and clover and, because of their symbiosis with the Rhizobium, they are grown in soils that have no need for energy-expensive nitrogenous fertilizer. These rhizobia live in two very different environments - most of the time they have to struggle along in the soil, and, in competition with all the other bugs and beasties, they have to grasp the rather scarce iron as best they can. Indeed Rhizobium has more methods for grabbing iron from their surrounds than almost any other known living thing. However, when the lucky few individual Rhizobium cells get into the root nodules, they live in luxury, fed, watered, pampered and protected by the host plant. But iron is still important here, since many of the proteins in the nodule, including the enzyme nitrogenase that drives the nitrogen fixation reaction, contain iron. We have been studying how Rhizobium obtains its iron and how it responds to it in their free-living state. This has shown that these bacteria use methods that are totally different from those that have been described in many other bacteria, including that genetic superstar, Escherichia coli. In brief, it seems that the Rhizobium are rather sophisticated since they switch their genes on and off in response to iron in two important forms (as iron-sulphur clusters and haem), rather than in response to the free metal itself, as occurs in E. coli. We believe that similar regulatory circuitry in response to iron may operate in many of Rhizobium's close relatives. These include some bacterial pathogens, including the potential bio-terror agent Brucella, and other genera of medical, environmental or biotechnological importance. In this new project we want to investigate the molecular mechanism of one of the key players in this unusual regulatory process / the one that senses and responds to iron in the form of haem. It seems that the ways in which the Rhizobium responds to iron when in the soil are very different to that when it is in the root nodule. Up to now, understanding the latter has been elusive, but we now have the opportunity / we think / to get our hands on a regulator that operates in the nodules. We plan to identify and start to characterise this new actor in what is turning out to be an intriguing story.

铁可能存在于灵魂中，也可能不存在于灵魂中，但它肯定存在于躯体中，作为所有活细胞功能的主要参与者。它需要在血液中输送氧气，帮助我们应对许多不同的毒素以及实现一千零一项其他重要的生化功能。这是因为铁具有特殊的化学性质，可以驱动各种氧化和其他产生能量的步骤，因此它存在于许多催化此类反应的酶中。然而，细胞内过量的铁可能非常有害，因为它同样的“氧化还原”特性也会产生一些非常讨厌的物质。这些所谓的“自由基”会损害细胞中的 DNA、脂质和蛋白质。因此，生物体将铁含量控制在适当的水平至关重要。我们正在研究一种叫做根瘤菌的细菌是如何实现这种所谓的“稳态”的，这种细菌之所以出名，主要是因为它在豆科植物的根部形成固氮根瘤。其中包括许多熟悉的作物，如豌豆、蚕豆和三叶草，由于它们与根瘤菌共生，它们生长在不需要能源昂贵的氮肥的土壤中。这些根瘤菌生活在两种截然不同的环境中——大多数时候它们必须在土壤中挣扎，并且在与所有其他虫子和野兽的竞争中，它们必须尽可能地抓住相当稀缺的铁。事实上，根瘤菌从周围环境中获取铁的方法比几乎任何其他已知的生物都要多。然而，当少数幸运的根瘤菌细胞进入根瘤时，它们生活得奢侈，受到寄主植物的喂养、浇水、呵护和保护。但铁在这里仍然很重要，因为根瘤中的许多蛋白质，包括驱动固氮反应的固氮酶，都含有铁。我们一直在研究根瘤菌如何获取铁以及它在自由生活状态下如何对铁做出反应。这表明这些细菌使用的方法与许多其他细菌（包括遗传巨星大肠杆菌）所描述的方法完全不同。简而言之，根瘤菌似乎相当复杂，因为它们会根据两种重要形式（如铁硫簇和血红素）的铁来打开和关闭基因，而不是像在大肠杆菌。我们相信，类似的对铁反应的调节电路可能在许多根瘤菌的近亲中发挥作用。其中包括一些细菌病原体，包括潜在的生物恐怖剂布鲁氏菌，以及其他具有医学、环境或生物技术重要性的属。在这个新项目中，我们想要研究这一不寻常的调节过程中关键参与者之一的分子机制/感知并响应血红素形式的铁的分子机制。看来根瘤菌在土壤中对铁的反应方式与在根瘤中的反应方式非常不同。到目前为止，对后者的理解仍然难以捉摸，但我们现在有机会/我们认为/获得在结节中运行的调节器。我们计划在一个有趣的故事中确定并开始塑造这位新演员。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sensing iron availability via the fragile [4Fe-4S] cluster of the bacterial transcriptional repressor RirA.

DOI：
10.1039/c7sc02801f
发表时间：
2017-12-01
期刊：
Chemical science
影响因子：
8.4
作者：
Pellicer Martinez MT;Martinez AB;Crack JC;Holmes JD;Svistunenko DA;Johnston AWB;Cheesman MR;Todd JD;Le Brun NE
通讯作者：
Le Brun NE

Computational reconstruction of iron- and manganese-responsive transcriptional networks in alpha-proteobacteria.

α-变形菌中铁和锰响应转录网络的计算重建。

DOI：
10.1371/journal.pcbi.0020163
发表时间：
2006-12-15
期刊：
PLOS COMPUTATIONAL BIOLOGY
影响因子：
4.3
作者：
Rodionov, Dmitry A.;Gelfand, Mikhail S.;Todd, Jonathan D.;Curson, Andrew R. J.;Johnston, Andrew W. B.
通讯作者：
Johnston, Andrew W. B.

Heme-responsive DNA binding by the global iron regulator Irr from Rhizobium leguminosarum.

来自豆科根瘤菌的全局铁调节因子 Irr 与血红素反应性 DNA 结合。