Fe–S clusters are essential cofactors involved in many reactions across all domains of life. Their biogenesis in Escherichia coli and other enterobacteria involves two machineries: Isc and Suf. Under conditions where cells operate with the Suf system, such as during oxidative stress or iron limitation, the entry of aminoglycosides is reduced, leading to resistance to these antibiotics. The transition between Isc and Suf machineries is controlled by the transcriptional regulator IscR. Here, we found that two small regulatory RNAs (sRNAs), FnrS and OxyS, control iscR expression by base pairing to the 5′-UTR of the iscR mRNA. These sRNAs act in opposite ways and in opposite conditions: FnrS, expressed in anaerobiosis, represses the expression of iscR while OxyS, expressed during oxidative stress, activates it. Using an E. coli strain experiencing protracted oxidative stress, we further demonstrate that iscR expression is rapidly and significantly enhanced in the presence of OxyS. Consequently, we further show that OxyS induces resistance to aminoglycosides during oxidative stress through regulation of Fe–S cluster biogenesis, revealing a major role for this sRNA.

中文翻译：

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小 RNA OxyS 通过控制大肠杆菌中的 Fe-S 簇生物发生，在氧化应激期间诱导对氨基糖苷类抗生素的抗性


Fe-S 簇是参与生命所有领域中许多反应的重要辅助因子。它们在大肠杆菌和其他肠杆菌中的生物发生涉及两种机制：Isc 和 Suf。在细胞与 Suf 系统一起运作的条件下，例如在氧化应激或铁限制期间，氨基糖苷类抗生素的进入减少，导致对这些抗生素的耐药性。Isc 和 Suf 机制之间的转换由转录调节因子 IscR 控制。在这里，我们发现两个小调节 RNA （sRNA） FnrS 和 OxyS 通过与 iscR mRNA 的 5′-UTR 碱基配对来控制 iscR 表达。这些 sRNA 以相反的方式和相反的条件下发挥作用：在厌氧中表达的 FnrS 抑制 iscR 的表达，而在氧化应激期间表达的 OxyS 激活它。使用经历长期氧化应激的大肠杆菌菌株，我们进一步证明在 OxyS 存在下 iscR 表达迅速而显着增强。因此，我们进一步表明，OxyS 通过调节 Fe-S 簇生物发生在氧化应激期间诱导对氨基糖苷类抗生素的抗性，揭示了该 sRNA 的主要作用。