ideR, an essential gene in Mycobacterium tuberculosis:: Role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response
ideR, an essential gene in Mycobacterium tuberculosis:: Role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response
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DOI：
10.1128/iai.70.7.3371-3381.2002
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发表时间：
2002-07-01
影响因子：
3.1
通讯作者：
Smith, I
中科院分区：
文献类型：
--
作者：
Rodriguez, GM;Voskuil, MI;Smith, I
分枝杆菌IdeR蛋白是DtxR（白喉毒素阻遏物）家族的金属依赖性调节剂。在铁存在的情况下，它与它所调控的基因的启动子区域中的特定DNA序列结合，从而控制它们的转录。在这项研究中，我们提供的证据，ideR是结核分枝杆菌的一个必需基因。在该分枝杆菌中，ideR在没有第二个功能性基因拷贝的情况下通常不能被破坏。然而，一种罕见的ideR突变体，其中ideR失活的致死作用被减轻了第二个网站的抑制突变，并表现出有限的铁同化能力。该菌株和衍生物的研究，其中IdeR的表达恢复允许我们确定表型的影响所造成的IdeR失活。使用DNA微阵列，铁依赖的转录谱的野生型，ideR突变体，和ideR互补的突变株进行了分析，铁和IdeR调控的基因进行了鉴定。这些基因编码多种蛋白质，包括推定的转运蛋白、参与铁载体合成和铁储存的蛋白质、PE/PPE家族的成员、参与毒力的膜蛋白、转录调节因子和参与脂质代谢的酶。
The mycobacterial IdeR protein is a metal-dependent regulator of the DtxR (diphtheria toxin repressor) family. In the presence of iron, it binds to a specific DNA sequence in the promoter regions of the genes that it regulates, thus controlling their transcription. In this study, we provide evidence that ideR is an essential gene in Mycobacterium tuberculosis. ideR cannot normally be disrupted in this mycobacterium in the absence of a second functional copy of the gene. However, a rare ideR mutant was obtained in which the lethal effects of ideR inactivation were alleviated by a second-site suppressor mutation and which exhibited restricted iron assimilation capacity. Studies of this strain and a derivative in which IdeR expression was restored allowed us to identify phenotypic effects resulting from ideR inactivation. Using DNA microarrays, the iron-dependent transcriptional profiles of the wild-type, ideR mutant, and ideR-complemented mutant strains were analyzed, and the genes regulated by iron and IdeR were identified. These genes encode a variety of proteins, including putative transporters, proteins involved in siderophore synthesis and iron storage, members of the PE/PPE family, a membrane protein involved in virulence, transcriptional regulators, and enzymes involved in lipid metabolism.