Ernst Florian D, Bereswill Stefan, Waidner Barbara, Stoof Jeroen, Mäder Ulrike, Kusters Johannes G, Kuipers Ernst J, Kist Manfred, van Vliet Arnoud H M, Homuth Georg
Institut für Mikrobiologie und Molekularbiologie, Ernst-Moritz-Arndt-Universität Greifswald, D-17487 Greifswald, Germany.
Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital of Freiburg, D-79140 Freiburg, Germany.
Microbiology (Reading). 2005 Feb;151(Pt 2):533-546. doi: 10.1099/mic.0.27404-0.
Intracellular iron homeostasis is a necessity for almost all living organisms, since both iron restriction and iron overload can result in cell death. The ferric uptake regulator protein, Fur, controls iron homeostasis in most Gram-negative bacteria. In the human gastric pathogen Helicobacter pylori, Fur is thought to have acquired extra functions to compensate for the relative paucity of regulatory genes. To identify H. pylori genes regulated by iron and Fur, we used DNA array-based transcriptional profiling with RNA isolated from H. pylori 26695 wild-type and fur mutant cells grown in iron-restricted and iron-replete conditions. Sixteen genes encoding proteins involved in metal metabolism, nitrogen metabolism, motility, cell wall synthesis and cofactor synthesis displayed iron-dependent Fur-repressed expression. Conversely, 16 genes encoding proteins involved in iron storage, respiration, energy metabolism, chemotaxis, and oxygen scavenging displayed iron-induced Fur-dependent expression. Several Fur-regulated genes have been previously shown to be essential for acid resistance or gastric colonization in animal models, such as those encoding the hydrogenase and superoxide dismutase enzymes. Overall, there was a partial overlap between the sets of genes regulated by Fur and those previously identified as growth-phase, iron or acid regulated. Regulatory patterns were confirmed for five selected genes using Northern hybridization. In conclusion, H. pylori Fur is a versatile regulator involved in many pathways essential for gastric colonization. These findings further delineate the central role of Fur in regulating the unique capacity of H. pylori to colonize the human stomach.
细胞内铁稳态对于几乎所有生物来说都是必需的，因为铁缺乏和铁过载都可能导致细胞死亡。铁摄取调节蛋白Fur控制着大多数革兰氏阴性菌的铁稳态。在人类胃部病原体幽门螺杆菌中，Fur被认为获得了额外功能以弥补调控基因相对较少的情况。为了鉴定受铁和Fur调控的幽门螺杆菌基因，我们使用基于DNA芯片的转录谱分析，该分析采用了从在铁限制和铁充足条件下生长的幽门螺杆菌26695野生型和fur突变体细胞中分离的RNA。16个编码参与金属代谢、氮代谢、运动性、细胞壁合成和辅因子合成的蛋白质的基因表现出铁依赖性的Fur抑制表达。相反，16个编码参与铁储存、呼吸作用、能量代谢、趋化性和氧清除的蛋白质的基因表现出铁诱导的Fur依赖性表达。先前已证明几个受Fur调控的基因对于动物模型中的耐酸性或胃部定殖至关重要，例如那些编码氢化酶和超氧化物歧化酶的基因。总体而言，受Fur调控的基因集与先前鉴定为受生长阶段、铁或酸调控的基因集之间存在部分重叠。使用Northern杂交对五个选定基因的调控模式进行了确认。总之，幽门螺杆菌Fur是一种多功能调节因子，参与许多对胃部定殖至关重要的途径。这些发现进一步阐明了Fur在调节幽门螺杆菌定殖人类胃部的独特能力中的核心作用。
