Silver S, Walderhaug M
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60680.
Microbiol Rev. 1992 Mar;56(1):195-228. doi: 10.1128/mr.56.1.195-228.1992.
Regulation of chromosomally determined nutrient cation and anion uptake systems shows important similarities to regulation of plasmid-determined toxic ion resistance systems that mediate the outward transport of deleterious ions. Chromosomally determined transport systems result in accumulation of K+, Mg2+, Fe3+, Mn2+, PO4(3-), SO4(2-), and additional trace nutrients, while bacterial plasmids harbor highly specific resistance systems for AsO2-, AsO4(3-), CrO4(2-), Cd2+, Co2+, Cu2+, Hg2+, Ni2+, SbO2-, TeO3(2-), Zn2+, and other toxic ions. To study the regulation of these systems, we need to define both the trans-acting regulatory proteins and the cis-acting target operator DNA regions for the proteins. The regulation of gene expression for K+ and PO4(3-) transport systems involves two-component sensor-effector pairs of proteins. The first protein responds to an extracellular ionic (or related) signal and then transmits the signal to an intracellular DNA-binding protein. Regulation of Fe3+ transport utilizes the single iron-binding and DNA-binding protein Fur. The MerR regulatory protein for mercury resistance both represses and activates transcription. The ArsR regulatory protein functions as a repressor for the arsenic and antimony(III) efflux system. Although the predicted cadR regulatory gene has not been identified, cadmium, lead, bismuth, zinc, and cobalt induce this system in a carefully regulated manner from a single mRNA start site. The cadA Cd2+ resistance determinant encodes an E1(1)-1E2-class efflux ATPase (consisting of two polypeptides, rather than the one earlier identified). Cadmium resistance is also conferred by the czc system (which confers resistances to zinc and cobalt in Alcaligenes species) via a complex efflux pump consisting of four polypeptides. These two cadmium efflux systems are not otherwise related. For chromate resistance, reduced cellular accumulation is again the resistance mechanism, but the regulatory components are not identified. For other toxic heavy metals (with few exceptions), there exist specific plasmid resistances that remain relatively terra incognita for future exploration of bioinorganic molecular genetics and gene regulation.
染色体决定的营养阳离子和阴离子摄取系统的调控，与质粒决定的有毒离子抗性系统的调控表现出重要的相似性，后者介导有害离子的外向运输。染色体决定的运输系统导致钾离子（K⁺）、镁离子（Mg²⁺）、铁离子（Fe³⁺）、锰离子（Mn²⁺）、磷酸根离子（PO₄³⁻）、硫酸根离子（SO₄²⁻）以及其他微量营养素的积累，而细菌质粒则含有针对亚砷酸根离子（AsO₂⁻）、砷酸根离子（AsO₄³⁻）、铬酸根离子（CrO₄²⁻）、镉离子（Cd²⁺）、钴离子（Co²⁺）、铜离子（Cu²⁺）、汞离子（Hg²⁺）、镍离子（Ni²⁺）、亚锑酸根离子（SbO₂⁻）、亚碲酸根离子（TeO₃²⁻）、锌离子（Zn²⁺）以及其他有毒离子的高度特异性抗性系统。为了研究这些系统的调控，我们需要确定反式作用调控蛋白和顺式作用靶标操纵子DNA区域。钾离子和磷酸根离子运输系统的基因表达调控涉及两组分传感器-效应器蛋白对。第一种蛋白对细胞外离子（或相关）信号作出反应，然后将信号传递给细胞内的DNA结合蛋白。铁离子运输调控利用单一的铁结合和DNA结合蛋白Fur。汞抗性的MerR调控蛋白既抑制又激活转录。ArsR调控蛋白作为砷和锑（III）外排系统的阻遏物发挥作用。尽管尚未鉴定出预测的cadR调控基因，但镉、铅、铋、锌和钴以精心调控的方式从单个mRNA起始位点诱导该系统。镉抗性决定因子cadA编码一种E1（1）-1E2类外排ATP酶（由两种多肽组成，而非先前鉴定的一种）。产碱杆菌属物种中的czc系统（赋予对锌和钴的抗性）也通过由四种多肽组成的复杂外排泵赋予镉抗性。这两种镉外排系统在其他方面没有关联。对于铬酸盐抗性，降低细胞内积累再次是抗性机制，但调控成分尚未确定。对于其他有毒重金属（少数例外情况除外），存在特定的质粒抗性，这对于生物无机分子遗传学和基因调控的未来探索而言仍是相对未知的领域。
