Université de Rennes I, Inserm U835, Upres EA2311, Biochimie Pharmaceutique, 2 avenue du Prof. Léon Bernard, 35043 Rennes, France.
Nucleic Acids Res. 2014 Apr;42(8):4892-905. doi: 10.1093/nar/gku149. Epub 2014 Feb 20.
The emergence of Staphylococcus aureus strains that are resistant to glycopeptides has led to alarming scenarios where serious staphylococcal infections cannot be treated. The bacterium expresses many small regulatory RNAs (sRNAs) that have unknown biological functions for the most part. Here we show that an S. aureus sRNA, SprX (alias RsaOR), shapes bacterial resistance to glycopeptides, the invaluable treatments for Methicillin-resistant staphylococcal infections. Modifying SprX expression levels influences Vancomycin and Teicoplanin glycopeptide resistance. Comparative proteomic studies have identified that SprX specifically downregulates stage V sporulation protein G, SpoVG. SpoVG is produced from the yabJ-spoVG operon and contributes to S. aureus glycopeptide resistance. SprX negatively regulates SpoVG expression by direct antisense pairings at the internal translation initiation signals of the second operon gene, without modifying bicistronic mRNA expression levels or affecting YabJ translation. The SprX and yabJ-spoVG mRNA domains involved in the interaction have been identified, highlighting the importance of a CU-rich loop of SprX in the control of SpoVG expression. We have shown that SpoVG might not be the unique SprX target involved in the glycopeptide resistance and demonstrated that the regulation of glycopeptide sensitivity involves the CU-rich domain of SprX. Here we report the case of a sRNA influencing antibiotic resistance of a major human pathogen.
金黄色葡萄球菌菌株对糖肽类抗生素的耐药性的出现，导致了严重的葡萄球菌感染无法治疗的可怕情况。该细菌表达了许多小的调控 RNA（sRNA），其中大部分具有未知的生物学功能。在这里，我们表明金黄色葡萄球菌 sRNA SprX（又名 RsaOR）影响细菌对糖肽类抗生素的耐药性，而糖肽类抗生素是治疗耐甲氧西林金黄色葡萄球菌感染的宝贵药物。改变 SprX 的表达水平会影响万古霉素和替考拉宁等糖肽类抗生素的耐药性。比较蛋白质组学研究表明，SprX 特异性地下调了阶段 V 孢子形成蛋白 G，即 SpoVG。SpoVG 由 yabJ-spoVG 操纵子产生，并有助于金黄色葡萄球菌对糖肽类抗生素的耐药性。SprX 通过在第二个操纵子基因的内部翻译起始信号处进行直接反义配对，负调控 SpoVG 的表达，而不改变双顺反子 mRNA 的表达水平或影响 YabJ 的翻译。已经确定了参与相互作用的 SprX 和 yabJ-spoVG mRNA 结构域，突出了 SprX 中富含 CU 的环在控制 SpoVG 表达中的重要性。我们已经表明，SpoVG 可能不是参与糖肽类抗生素耐药性的唯一 SprX 靶标，并证明了调节糖肽类抗生素敏感性涉及 SprX 的富含 CU 的结构域。在这里，我们报告了一种 sRNA 影响主要人类病原体抗生素耐药性的情况。
