Nies D H
Institut für Pflanzenphysiologie und Mikrobiologie, Freie Universität Berlin, Germany.
Plasmid. 1992 Jan;27(1):17-28. doi: 10.1016/0147-619x(92)90003-s.
The divalent cations of cobalt, zinc, and nickel are essential nutrients for bacteria, required as trace elements at nanomolar concentrations. However, at micro- or millimolar concentrations, Co2+, Zn2+, and Ni2+ (and "bad ions" without nutritional roles such as Cd2+) are toxic. These cations are transported into the cell by constitutively expressed divalent cation uptake systems of broad specificity, i.e., basically Mg2+ transport systems. Therefore, in case of a heavy metal stress, uptake of the toxic ions cannot be reduced by a simple down-regulation of the transport activity. As a response to the resulting metal toxicity, metal resistance determinants evolved which are mostly plasmid-encoded in bacteria. In contrast to that of the cation Hg2+, chemical reduction of Co2+, Zn2+, Ni2+, and Cd2+ by the cell is not possible or sensible. Therefore, other than mutations limiting the ion range of the uptake system, only two basic mechanisms of resistance to these ions are possible (and were developed by evolution): intracellular complexation of the toxic metal ion is mainly used in eucaryotes; the cadmium-binding components are phytochelatins in plant and yeast cells and metallothioneins in animals, plants, and yeasts. In contrast, reduced accumulation based on an active efflux of the cation is the primary mechanism developed in procaryotes and perhaps in Saccharomyces cerevisiae. All bacterial cation efflux systems characterized to date are plasmid-encoded and inducible but differ in energy-coupling and in the number and types of proteins involved in metal transport and in regulation. In the gram-positive multiple-metal-resistant bacterium Staphylococcus aureus, Cd2+ (and probably Zn2+) efflux is catalyzed by the membrane-bound CadA protein, a P-type ATPase. However, a second protein (CadC) is required for full resistance and a third one (CadR) is hypothesized for regulation of the resistance determinant. The czc determinant from the gram-negative multiple-metal-resistant bacterium Alcaligenes eutrophus encodes proteins required for Co2+, Zn2+, and Cd2+ efflux (CzcA, CzcB, and CzcC) and regulation of the czc determinant (CzcD). In the current working model CzcA works as a cation-proton antiporter, CzcB as a cation-binding subunit, and CzcC as a modifier protein required to change the substrate specificity of the system from Zn2+ only to Co2+, Zn2+, and Cd2+.
钴、锌和镍的二价阳离子是细菌必需的营养素，作为微量元素以纳摩尔浓度存在。然而，在微摩尔或毫摩尔浓度下，Co2+、Zn2+和Ni2+（以及没有营养作用的“有害离子”，如Cd2+）具有毒性。这些阳离子通过组成型表达的具有广泛特异性的二价阳离子摄取系统进入细胞，即基本上是Mg2+转运系统。因此，在重金属胁迫的情况下，有毒离子的摄取不能通过简单下调转运活性来减少。作为对由此产生的金属毒性的一种反应，进化出了金属抗性决定因素，这些因素在细菌中大多由质粒编码。与阳离子Hg2+不同，细胞对Co2+、Zn2+、Ni2+和Cd2+进行化学还原是不可能的或不明智的。因此，除了限制摄取系统离子范围的突变外，对这些离子的抗性只有两种基本机制（并且是进化产生的）：在真核生物中主要使用有毒金属离子的细胞内络合；镉结合成分在植物和酵母细胞中是植物螯合肽，在动物、植物和酵母中是金属硫蛋白。相比之下，基于阳离子主动外排的积累减少是原核生物以及可能在酿酒酵母中发展出的主要机制。迄今为止所表征的所有细菌阳离子外排系统都是由质粒编码且可诱导的，但在能量偶联以及参与金属转运和调节的蛋白质数量和类型方面存在差异。在革兰氏阳性多重金属抗性细菌金黄色葡萄球菌中，Cd2+（可能还有Zn2+）的外排由膜结合的CadA蛋白催化，CadA蛋白是一种P型ATP酶。然而，完全抗性需要第二种蛋白质（CadC），并且假设第三种蛋白质（CadR）用于调节抗性决定因素。来自革兰氏阴性多重金属抗性细菌嗜碱产碱杆菌的czc决定因素编码Co2+、Zn2+和Cd2+外排所需的蛋白质（CzcA、CzcB和CzcC）以及czc决定因素的调节蛋白（CzcD）。在当前的工作模型中，CzcA作为阳离子 - 质子反向转运体起作用，CzcB作为阳离子结合亚基，CzcC作为将系统底物特异性从仅Zn2+改变为Co2+、Zn2+和Cd2+所需的修饰蛋白。
