Department of Microbiology, North Carolina State University, Raleigh, NC 27695-7615, USA.
BMC Microbiol. 2011 Oct 21;11:236. doi: 10.1186/1471-2180-11-236.
The Ferric uptake regulator (Fur) is a transcriptional regulator that controls iron homeostasis in bacteria. Although the regulatory role of Fur in Escherichia coli is well characterized, most of the studies were conducted under routine culture conditions, i.e., in ambient oxygen concentration. To reveal potentially novel aspects of the Fur regulon in Salmonella enterica serovar Typhimurium under oxygen conditions similar to that encountered in the host, we compared the transcriptional profiles of the virulent wild-type strain (ATCC 14028s) and its isogenic Δfur strain under anaerobic conditions.
Microarray analysis of anaerobically grown Δfur S. Typhimurium identified 298 differentially expressed genes. Expression of several genes controlled by Fnr and NsrR appeared to be also dependent on Fur. Furthermore, Fur was required for the activity of the cytoplasmic superoxide disumutases (MnSOD and FeSOD). The regulation of FeSOD gene, sodB, occurred via small RNAs (i.e., the ryhB homologs, rfrA and rfrB) with the aid of the RNA chaperone Hfq. The transcription of sodA was increased in Δfur; however, the enzyme was inactive due to the incorporation of iron instead of manganese in SodA. Additionally, in Δfur, the expression of the gene coding for the ferritin-like protein (ftnB) was down-regulated, while the transcription of the gene coding for the nitric oxide (NO·) detoxifying flavohemoglobin (hmpA) was up-regulated. The promoters of ftnB and hmpA do not contain recognized Fur binding motifs, which indicated their probable indirect regulation by Fur. However, Fur activation of ftnB was independent of Fnr. In addition, the expression of the gene coding for the histone-like protein, H-NS (hns) was increased in Δfur. This may explain the observed down-regulation of the tdc operon, responsible for the anaerobic degradation of threonine, and ftnB in Δfur.
This study determined that Fur is a positive factor in ftnB regulation, while serving to repress the expression of hmpA. Furthermore, Fur is required for the proper expression and activation of the antioxidant enzymes, FeSOD and MnSOD. Finally, this work identified twenty-six new targets of Fur regulation, and demonstrates that H-NS repressed genes are down-regulated in Δfur.
铁摄取调控因子（Fur）是一种转录调控因子，可控制细菌中的铁稳态。尽管 Fur 在大肠杆菌中的调控作用已得到很好的描述，但大多数研究都是在常规培养条件下进行的，即在环境氧浓度下进行的。为了揭示沙门氏菌属 Typhimurium 中 Fur 调控子在类似于宿主中遇到的氧气条件下的潜在新方面，我们比较了毒力野生型菌株（ATCC 14028s）及其同工基因缺失菌株（Δfur）在厌氧条件下的转录谱。
微阵列分析表明，厌氧生长的Δfur S. Typhimurium 中有 298 个差异表达基因。Fnr 和 NsrR 控制的几个基因的表达似乎也依赖于 Fur。此外，Fur 对细胞质超氧化物歧化酶（MnSOD 和 FeSOD）的活性是必需的。FeSOD 基因 sodB 的调控是通过小 RNA（即 rhB 同源物 rfrA 和 rfrB）在 RNA 伴侣 Hfq 的帮助下完成的。Δfur 中 sodA 的转录增加；然而，由于 SodA 中掺入了铁而不是锰，该酶失活。此外，在Δfur 中，编码铁蛋白样蛋白（ftnB）的基因表达下调，而编码一氧化氮（NO·）解毒黄素蛋白（hmpA）的基因转录上调。ftnB 和 hmpA 的启动子不包含公认的 Fur 结合基序，这表明它们可能是 Fur 的间接调控。然而， Fur 对 ftnB 的激活与 Fnr 无关。此外，编码组蛋白样蛋白 H-NS（hns）的基因在Δfur 中表达增加。这可以解释在Δfur 中观察到的 tdc 操纵子（负责苏氨酸的厌氧降解）和 ftnB 的下调表达。
本研究确定 Fur 是 ftnB 调节的正因子，同时抑制 hmpA 的表达。此外，Fur 是抗氧化酶 FeSOD 和 MnSOD 适当表达和激活所必需的。最后，本工作确定了 Fur 调节的 26 个新靶标，并证明了 H-NS 抑制的基因在Δfur 中下调。
