Institute for Cell & Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Institute for Cell & Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Adv Microb Physiol. 2017;70:315-379. doi: 10.1016/bs.ampbs.2017.01.003. Epub 2017 Feb 13.
The metals manganese, iron, cobalt, nickel, copper and zinc are essential for almost all bacteria, but their precise metal requirements vary by species, by ecological niche and by growth condition. Bacteria thus must acquire each of these essential elements in sufficient quantity to satisfy their cellular demand, but in excess these same elements are toxic. Metal toxicity has been exploited by humanity for centuries, and by the mammalian immune system for far longer, yet the mechanisms by which these elements cause toxicity to bacteria are not fully understood. There has been a resurgence of interest in metal toxicity in recent decades due to the problematic spread of antibiotic resistance amongst bacterial pathogens, which has led to an increased research effort to understand these toxicity mechanisms at the molecular level. A recurring theme from these studies is the role of intermetal competition in bacterial metal toxicity. In this review, we first survey biological metal usage and introduce some fundamental chemical concepts that are important for understanding bacterial metal usage and toxicity. Then we introduce a simple model by which to understand bacterial metal homeostasis in terms of the distribution of each essential metal ion within cellular 'pools', and dissect how these pools interact with each other and with key proteins of bacterial metal homeostasis. Finally, using a number of key examples from the recent literature, we look at specific metal toxicity mechanisms in model bacteria, demonstrating the role of metal-metal competition in the toxicity mechanisms of diverse essential metals.
锰、铁、钴、镍、铜和锌等金属对几乎所有细菌都是必需的，但它们的具体金属需求因物种、生态位和生长条件而异。因此，细菌必须获取足够数量的每种必需元素来满足其细胞需求，但这些相同的元素过量时会有毒性。人类几个世纪以来一直在利用金属毒性，哺乳动物的免疫系统利用这种毒性的时间更长，但这些元素导致细菌毒性的确切机制尚未完全了解。近几十年来，由于细菌病原体对抗生素耐药性的问题不断蔓延，人们对金属毒性的兴趣再次高涨，这导致人们加大了研究力度，以期在分子水平上了解这些毒性机制。这些研究的一个反复出现的主题是金属间竞争在细菌金属毒性中的作用。在这篇综述中，我们首先调查了生物金属的使用情况，并介绍了一些对于理解细菌金属使用和毒性很重要的基本化学概念。然后，我们引入了一个简单的模型，用于根据每个必需金属离子在细胞“池”中的分布来理解细菌金属稳态，并剖析这些池如何相互作用以及与细菌金属稳态的关键蛋白相互作用。最后，我们使用来自近期文献中的一些关键实例，研究了模型细菌中的特定金属毒性机制，展示了金属-金属竞争在多种必需金属毒性机制中的作用。
