Global iron-dependent gene regulation in Escherichia coli -: A new mechanism for iron homeostasis
Global iron-dependent gene regulation in Escherichia coli -: A new mechanism for iron homeostasis
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DOI：
10.1074/jbc.m303381200
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发表时间：
2003-08-08
影响因子：
4.8
通讯作者：
Andrews, SC
中科院分区：
文献类型：
--
作者：
McHugh, JP;Rodríguez-Quiñones, F;Andrews, SC
生物体通常通过增加其吸收铁的能力和消耗细胞内铁储存来应对铁缺乏。大肠杆菌，其中铁代谢是特别好理解，包含至少7个铁的收购系统编码的35个铁抑制基因。这种铁依赖性抑制是由转录抑制因子Fur（铁摄取调节）介导的，Fur还控制参与其他过程的基因，如铁储存、三羧酸循环、致病性和氧化还原应激抗性。我们的基于宏芯片的铁和毛皮依赖基因表达的全球分析在E。大肠杆菌已经揭示了几个新的皮毛抑制基因可能指定至少三个额外的铁转运途径。有趣的是，铁和毛皮诱导了大量的能量代谢基因。这些基因中的许多编码富铁呼吸复合物。这种铁和毛皮依赖性调节似乎代表了一种新的铁稳态机制，其中许多含铁蛋白质的合成在铁限制条件下被抑制。因此，这一机制解释了毛皮突变体的低铁含量，并解释了E。大肠杆菌可以调节其铁需求。Fe-55标记E.大肠杆菌蛋白揭示了毛皮突变体的铁蛋白组成的显著降低，可见光和EPR光谱显示螯合剂处理的野生型和/或毛皮突变体的细胞色素B和d水平以及铁硫簇含量的显著降低，与阵列和定量RT-PCR数据很好地相关。总之，这些结果为Fe 2 +-Fur复合物调节细胞内铁消耗提供了令人信服的证据。
Organisms generally respond to iron deficiency by increasing their capacity to take up iron and by consuming intracellular iron stores. Escherichia coli, in which iron metabolism is particularly well understood, contains at least 7 iron-acquisition systems encoded by 35 iron-repressed genes. This Fe-dependent repression is mediated by a transcriptional repressor, Fur ( ferric uptake regulation), which also controls genes involved in other processes such as iron storage, the Tricarboxylic Acid Cycle, pathogenicity, and redox-stress resistance. Our macroarray-based global analysis of iron- and Fur-dependent gene expression in E. coli has revealed several novel Fur-repressed genes likely to specify at least three additional iron- transport pathways. Interestingly, a large group of energy metabolism genes was found to be iron and Fur induced. Many of these genes encode iron- rich respiratory complexes. This iron- and Fur-dependent regulation appears to represent a novel iron-homeostatic mechanism whereby the synthesis of many iron- containing proteins is repressed under iron- restricted conditions. This mechanism thus accounts for the low iron contents of fur mutants and explains how E. coli can modulate its iron requirements. Analysis of Fe-55-labeled E. coli proteins revealed a marked decrease in iron- protein composition for the fur mutant, and visible and EPR spectroscopy showed major reductions in cytochrome b and d levels, and in iron- sulfur cluster contents for the chelator-treated wild-type and/or fur mutant, correlating well with the array and quantitative RT-PCR data. In combination, the results provide compelling evidence for the regulation of intracellular iron consumption by the Fe2+-Fur complex.