Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors
Transcriptional and translational control of the mlr operon, which confers resistance to seven classes of protein synthesis inhibitors
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DOI：
10.1128/aac.01583-07
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发表时间：
2008-05-01
影响因子：
4.9
通讯作者：
Mankin, Alexander S.
中科院分区：
文献类型：
--
作者：
Smith, Lisa K.;Mankin, Alexander S.
在耐甲氧西林金黄色葡萄球菌菌株CM 05的染色体中，甲基转移酶基因cfr（B）和cfr彼此相邻。对菌株CM 05染色体中的MLR、（B）和cfr基因的转录组织的分析表明，这两个基因被组织成一个操纵子，命名为mLR（用于修饰核糖体大亚基），其由MLR（B）启动子控制。分析的翻译控制和诱导的mlr操纵子中的cfr（B）和cfr基因表明，尽管存在推定的调控短开放阅读框，这两个基因的组成型表达。mlr操纵子中编码的两种甲基转移酶的联合作用导致23S rRNA中两个特定残基A2058和A2503的修饰，并使细胞对靶向核糖体大亚基的所有临床有用的抗生素产生抗性。此外，同时修饰两个rRNA位点协同增强对16元环大环内酯类的抗性。
The methyltransferase genes erm(B) and cfr are adjacent to each other in the chromosome of methicillin-resistant Staphylococcus aureus strain CM05. Analyses of the transcriptional organization of the erm,(B) and cfr genes in the chromosome of strain CM05 showed that the two genes are organized into an operon, designated mlr (for modification of the large ribosomal subunit), which is controlled by the erm(B) promoter. Analysis of the translation control and the inducibility of the erm(B) and cfr genes in the mlr operon showed that despite the presence of putative regulatory short open reading frames, both genes are expressed constitutively. The combined action of the two methyltransferases encoded in the mlr operon results in modification of two specific residues in 23S rRNA, A2058 and A2503, and renders cells resistant to all clinically useful antibiotics that target the large ribosomal subunit. Furthermore, simultaneous modification of both rRNA sites synergistically enhances resistance to 16-member-ring macrolides.