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Abstract：
Organisms need sufficient intracellular iron to maintain biological processes. However, cells can be damaged by excessive iron-induced oxidation stress. Therefore, iron homeostasis must be strictly regulated. In general, bacteria have evolved complex mechanisms to maintain iron homeostasis. In this study, we showed that Pseudoalteromonas sp. R3 has four sets of iron uptake systems. Among these, the siderophore pyoverdine-dependent iron uptake system and the ferrous iron transporter Feo system are more important for iron uptake and prodiginine biosynthesis. Stringent starvation protein SspA positively controls iron uptake and iron-dependent prodiginine biosynthesis by regulating the expression of all iron uptake systems. In turn, the expression of SspA can be induced and repressed by extracellular iron deficiency and excess, respectively. Interestingly, extracytoplasmic function sigma factor PvdS also regulates iron uptake and prodiginine production and responds to extracellular iron levels, exhibiting a similar phenomenon as SspA. Notably, not only do SspA and PvdS function independently, but they can also compensate for each other, and their expression can be affected by the other. All of these findings demonstrate that SspA and PvdS coordinate iron homeostasis and prodiginine biosynthesis in strain R3. More importantly, our results also showed that SspA and PvdS homologs in Pseudomonas aeruginosa PAO1 have similar functions in iron uptake to their counterparts in Pseudoalteromonas, suggesting that coordination between SspA and PvdS on iron homeostasis could be conserved in typical Gram-negative bacteria. Since master regulation of iron homeostasis is extremely important for cell survival, this cross talk between SspA and PvdS may be environmentally significant. IMPORTANCE Both deficiency and excess of intracellular iron can be harmful, and thus, the iron homeostasis needs to be tightly regulated in organisms. At present, the ferric uptake regulator (Fur) is the best-characterized regulator involved in bacterial iron homeostasis, while other regulators of iron homeostasis remain to be further explored. Here, we demonstrated that the stringent starvation protein SspA and the extracytoplasmic function sigma factor PvdS coordinate iron uptake and iron-dependent prodiginine biosynthesis in Pseudoalteromonas sp. R3. These two regulators work independently, but their functions can compensate for the other and their expression can be affected by the other. Moreover, their expression can be activated and repressed by extracellular iron deficiency and excess, respectively. Notably, SspA and PvdS homologs in Pseudomonas aeruginosa PAO1 exhibit similar functions in iron uptake to their counterparts in Pseudoalteromonas, suggesting that this novel fine-tuned mode of iron homeostasis could be conserved in typical Gram-negative bacteria.
摘要：
生物体需要足够的细胞内铁来维持生物过程。然而,细胞可被过度的铁诱导的氧化应激损伤。因此,铁稳态必须严格调节。总的来说,细菌已经进化出复杂的机制来维持铁稳态。在这项研究中,我们显示假交替单胞菌。R3具有四组铁吸收系统。其中,铁载体pyoverdine依赖的铁吸收系统和亚铁转运蛋白Feo系统对于铁吸收和prodiginine生物合成更为重要。严格的饥饿蛋白SspA通过调节所有铁摄取系统的表达来积极控制铁摄取和铁依赖性的prodiginine生物合成。反过来,细胞外铁缺乏和过多可以诱导和抑制SspA的表达，分别。有趣的是,细胞质外功能sigma因子PvdS还调节铁摄取和prodiginine产生，并响应细胞外铁水平，表现出与SspA类似的现象。值得注意的是,SspA和PvdS不仅独立运行，但是它们也可以相互补偿，他们的表达会受到对方的影响。所有这些发现表明SspA和PvdS协调菌株R3中的铁稳态和prodiginine生物合成。更重要的是,我们的结果还表明，铜绿假单胞菌PAO1中的SspA和PvdS同系物在铁吸收方面与假单胞菌中的对应物具有相似的功能，表明SspA和PvdS之间在铁稳态上的协调可以在典型的革兰氏阴性细菌中保守。由于铁稳态的主要调节对细胞存活极为重要,SspA和PvdS之间的这种串扰可能对环境具有重要意义。重要性细胞内铁的缺乏和过量都可能是有害的，因此，生物体内的铁稳态需要受到严格的调节。目前,三价铁摄取调节剂（Fur）是细菌铁稳态的最佳特征调节剂，而铁稳态的其他调节剂仍有待进一步探索。这里,我们证明了严格的饥饿蛋白SspA和胞质外功能sigma因子PvdS在假交替单胞菌中协调铁的吸收和铁依赖性的前列腺碱的生物合成。R3.这两个监管机构独立工作，但是它们的功能可以补偿对方，它们的表达可以受到对方的影响。此外，它们的表达可以被细胞外铁缺乏和过量激活和抑制，分别。值得注意的是,铜绿假单胞菌PAO1中的SspA和PvdS同系物在铁吸收方面表现出与假单胞菌中的对应物相似的功能，这表明这种新型的铁稳态微调模式可以在典型的革兰氏阴性菌中得到保留。
