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

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。它需要在血液中运输氧气，帮助我们应对许多不同的毒素，以及其他许多基本的生化功能。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能量生成步骤，因此它存在于许多催化这些反应的酶中。然而，细胞内过量的铁可能是非常有害的，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”可以破坏细胞中的DNA、脂质和蛋白质。因此，生物将铁的含量控制在合适的水平上是至关重要的。我们正在研究这种所谓的“体内平衡”是如何在一种叫做根瘤菌的细菌中实现的，这种细菌的主要名声在于它在豆科植物的根上形成固氮结节。这些包括许多我们熟悉的作物，如豌豆、豆类和三叶草，由于它们与根瘤菌的共生关系，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，在与所有其他昆虫和动物的竞争中，它们必须尽可能地抓住相当稀缺的铁。事实上，根瘤菌比其他任何已知的生物都有更多的方法从周围环境中获取铁。然而，当少数幸运的根瘤菌细胞进入根瘤后，它们在寄主植物的喂养、浇灌、呵护和保护下过着奢侈的生活。但铁在这里仍然很重要，因为结节中的许多蛋白质，包括驱动固氮反应的酶氮酶，都含有铁。我们一直在研究根瘤菌是如何获得铁的，以及它在自由生活状态下是如何对铁做出反应的。这表明，这些细菌使用的方法与许多其他细菌完全不同，包括遗传超级明星大肠杆菌。简而言之，根瘤菌似乎相当复杂，因为它们对两种重要形式的铁（如铁硫簇和血红素）作出反应，而不是像大肠杆菌那样对游离金属本身作出反应，从而开启和关闭它们的基因。我们相信类似的调控电路响应铁可能在许多根瘤菌的近亲操作。其中包括一些细菌性病原体，包括潜在的生物恐怖制剂布鲁氏菌，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，我们想要研究在这个不寻常的调节过程中一个关键角色的分子机制，这个角色以血红素的形式感知和响应铁。似乎根瘤菌对土壤中铁的反应方式与根瘤中铁的反应方式大不相同。到目前为止，理解后者一直是难以捉摸的，但我们现在有机会/我们认为/得到一个在结节中运作的调节器。我们计划在一个有趣的故事中确定并开始描述这个新角色。

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.