Little is known about the mechanisms by which ileS mutations induce vancomycin tolerance in Staphylococcus aureus. This study showed that transcriptome profiles were similar in vancomycin-tolerant mutants and the IleRS-inhibitor-treated parent. Notably, ileS and relA, which induce a stringent response, were upregulated. The same mechanism was responsible for cross-tolerance to vancomycin and ciprofloxacin. These findings suggest that the accumulation of uncharged isoleucyl-tRNA following ileS mutations in S. aureus was responsible for drug tolerance.

中文翻译：

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RNA测序确定了由ileS突变诱导的耐万古霉素和环丙沙星的金黄色葡萄球菌的常见生理现象。

关于ileS突变诱导金黄色葡萄球菌对万古霉素耐受的机制鲜为人知。这项研究表明，耐万古霉素的突变体和接受IleRS抑制剂治疗的亲本的转录组谱相似。值得注意的是，诱导严格反应的ileS和relA被上调。相同的机制对万古霉素和环丙沙星具有交叉耐受性。这些发现表明，金黄色葡萄球菌中的ileS突变后不带电荷的异亮氨酰tRNA的积累是药物耐受性的原因。