Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.

中文翻译：

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葡萄球菌中 sRNA 控制的铁保留反应

金黄色葡萄球菌是一种人类机会主义病原体，它会调整其新陈代谢以应对宿主体内的铁缺乏。我们调查了小型非编码 RNA (sRNA) 在决定这一过程中的潜在作用。一个单一的 sRNA，在此命名为 IsrR，是从具有标记突变库的竞争分析中出现的，这是铁饥饿期间所必需的。IsrR 被铁抑制并预测靶向表达含铁酶的 mRNA。其中，我们证明了 IsrR 下调了催化厌氧硝酸盐呼吸的酶的 mRNA 的翻译。IsrR 序列揭示了三个单链富含 C 的区域 (CRR)。突变和结构分析表明这些 CRR 根据目标的不同贡献。我们还报告说，在小鼠败血症模型中，金黄色葡萄球菌的完全致死需要 IsrR，强调其作为感染期间细菌存活的保铁反应的主要贡献者的作用。IsrR 在葡萄球菌中是保守的，但它不是变形菌 sRNA RyhB 的直系同源物，也不是其他特征性的 sRNA 下调含铁酶的 mRNA。值得注意的是，这些不同的 sRNA 调节共同的目标，说明基于 RNA 的调节提供了最佳的进化解决方案，以在铁缺乏时提高细菌的适应性。