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首页> 外文期刊>The FEBS journal >Ribosomal RNA methyltransferases contribute to Staphylococcusaureus virulence
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Ribosomal RNA methyltransferases contribute to Staphylococcusaureus virulence

机译:核糖体RNA甲基转移酶有助于葡萄球菌的致病性

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Post-transcriptional modifications in rRNA, such as methylation, are observed in functionally important regions of the ribosome. The methyltransferases responsible for these modifications work as housekeeping enzymes to fine-tune ribosomal function, and the roles of some methyltransferases become more evident under stress conditions. Recently, the 16S rRNA methyltransferases RsmI and RsmH, which are responsible for cytidine dimethylation at the decoding center of the ribosome, were identified in Escherichiacoli. The physiological relevance of the rRNA modification, however, remains obscure. We identified rsmI and rsmH as novel virulence genes in Staphylococcusaureus using a silkworm infection model. These genes induced 2-O- and N-4-methylations, respectively, of m(4)Cm1412 of S.aureus 16S rRNA. Deletion of either rsmI or rsmH in S.aureus attenuated the virulence of S.aureus in silkworms, and led to its sensitivity to oxidative stress. Dual luciferase assay revealed that the double-knockout strain exhibited decreased translational fidelity under oxidative stress conditions. In addition, administration of N-acetyl-l-cysteine, a free-radical scavenger, restored the killing ability of the double-knockout strain against silkworms. These findings suggest that the methyl-modifications of cytidine at position 1412 in 16S rRNA contribute to S.aureus animal killing by conferring resistance to oxidative stress in host animals.
机译:在核糖体的功能重要区域中观察到rRNA的转录后修饰,例如甲基化。负责这些修饰的甲基转移酶作为管家酶来微调核糖体功能,某些甲基转移酶的作用在压力条件下变得更加明显。最近,在大肠杆菌中鉴定了负责核糖体解码中心胞苷二甲基化的16S rRNA甲基转移酶RsmI和RsmH。然而,rRNA修饰的生理相关性仍然不清楚。我们使用家蚕感染模型将rsmI和rsmH确定为葡萄球菌中的新型毒力基因。这些基因分别诱导金黄色葡萄球菌16S rRNA的m(4)Cm1412的2-O-和N-4-甲基化。金黄色葡萄球菌中rsmI或rsmH的缺失减弱了家蚕中金黄色葡萄球菌的毒力,并导致其对氧化应激的敏感性。双重荧光素酶测定法显示,双敲除菌株在氧化应激条件下表现出降低的翻译保真度。另外,施用自由基清除剂N-乙酰基-1-半胱氨酸恢复了双敲除菌株对蚕的杀灭能力。这些发现表明16S rRNA中1412位的胞苷的甲基修饰通过赋予宿主动物抗氧化性而有助于金黄色葡萄球菌的杀死。

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