Moore Charles M, Gaballa Ahmed, Hui Monica, Ye Rick W, Helmann John D
Department of Microbiology, Cornell University, Ithaca, NY 14853, USA.
Mol Microbiol. 2005 Jul;57(1):27-40. doi: 10.1111/j.1365-2958.2005.04642.x.
Metal ion homeostasis is regulated principally by metalloregulatory proteins that control metal ion uptake, storage and efflux genes. We have used transcriptional profiling to survey Bacillus subtilis for genes that are rapidly induced by exposure to high levels of metal ions including Ag(I), Cd(II), Cu(II), Ni(II) and Zn(II) and the metalloid As(V). Many of the genes affected by metal stress were controlled by known metalloregulatory proteins (Fur, MntR, PerR, ArsR and CueR). Additional metal-induced genes are regulated by two newly defined metal-sensing ArsR/SmtB family repressors: CzrA and AseR. CzrA represses the CadA efflux ATPase and the cation diffusion facilitator CzcD and this repression is alleviated by Zn(II), Cd(II), Co(II), Ni(II) and Cu. CadA is the major determinant for Cd(II) resistance, while CzcD protects the cell against elevated levels of Zn(II), Cu, Co(II) and Ni(II). AseR negatively regulates itself and AseA, an As(III) efflux pump which contributes to arsenite resistance in cells lacking a functional ars operon. Our results extend the range of identified effectors for the As(III)-sensor ArsR to include Cd(II) and Ag(I) and for the Cu-sensor CueR to include Ag(I) and, weakly, Cd(II) and Zn(II). In addition to systems dedicated to metal homeostasis, specific metal stresses also strongly induced pathways related to cysteine, histidine and arginine metabolism.
金属离子稳态主要由控制金属离子摄取、储存和外排基因的金属调节蛋白来调节。我们利用转录谱分析来检测枯草芽孢杆菌中那些因暴露于高水平金属离子（包括Ag(I)、Cd(II)、Cu(II)、Ni(II)、Zn(II)和类金属As(V)）而被快速诱导的基因。许多受金属胁迫影响的基因由已知的金属调节蛋白（Fur、MntR、PerR、ArsR和CueR）控制。另外一些金属诱导基因则由两个新定义的金属感应ArsR/SmtB家族阻遏蛋白CzrA和AseR调节。CzrA抑制CadA外排ATP酶和阳离子扩散促进蛋白CzcD，而Zn(II)、Cd(II)、Co(II)、Ni(II)和Cu可缓解这种抑制作用。CadA是Cd(II)抗性的主要决定因素，而CzcD可保护细胞免受高水平Zn(II)、Cu、Co(II)和Ni(II)的影响。AseR负向调节其自身以及AseA，AseA是一种As(III)外排泵，在缺乏功能性ars操纵子的细胞中有助于抗亚砷酸盐。我们的结果扩展了已确定的As(III)传感器ArsR的效应物范围，使其包括Cd(II)和Ag(I)，以及Cu传感器CueR的效应物范围，使其包括Ag(I)，以及较弱的Cd(II)和Zn(II)。除了专门用于金属稳态的系统外，特定的金属胁迫还强烈诱导了与半胱氨酸、组氨酸和精氨酸代谢相关的途径。
