Mechanism of action of oxazolidinones: Effects of linezolid and eperezolid on translation reactions
Mechanism of action of oxazolidinones: Effects of linezolid and eperezolid on translation reactions
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DOI：
10.1128/aac.41.10.2132
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发表时间：
1997-10-01
影响因子：
4.9
通讯作者：
Buysse, JM
中科院分区：
文献类型：
--
作者：
Shinabarger, DL;Marotti, KR;Buysse, JM
恶唑烷酮类化合物是一类新的合成抗生素，对革兰氏阳性菌有较好的抗菌活性。用敏感的大肠杆菌UC 6782株进行的实验表明，在体内蛋白质合成均被利奈唑胺（以前称为U-100592）和利奈唑胺（以前称为U-100766）抑制。大肠杆菌，表现出50%抑制浓度（IC（50））分别为1.8和2.5 μ M。证明抑制由噬菌体MS 2 RNA指导的体外翻译的能力在很大程度上取决于加入到测定中的RNA的量。对于依哌唑胺，128 μ g/ml的RNA产生50 μ M的IC 50，而32 μ g/ml的浓度产生20 μ M的IC 50。在利奈唑胺抑制实验中研究较低的RNA模板浓度显示，每毫升32和8 μ g MS 2噬菌体RNA分别产生24和15 μ M的IC（50）。翻译起始抑制剂春雷霉素（kasugamycin）而非链霉素（streptomycin）共享此现象。恶唑烷酮均不抑制N-甲酰甲硫氨酰-tRNA的形成、延伸或细菌翻译的终止反应。恶唑烷酮似乎在蛋白质合成的起始阶段抑制细菌翻译。
The oxazolidinones are a new class of synthetic antibiotics with good activity against gram-positive pathogenic bacteria, Experiments with a susceptible Escherichia coli strain, UC6782, demonstrated that in vivo protein synthesis was inhibited by both eperezolid (formerly U-100592) and linezolid (formerly U-100766), Both linezolid and eperezolid were potent inhibitors of cell-free transcription-translation in E. coli, exhibiting 50% inhibitory concentrations (IC(50)s) of 1.8 and 2.5 mu M, respectively. The ability to demonstrate inhibition of in vitro translation directed by phage MS2 RNA was greatly dependent upon the amount of RNA added to the assay, For eperezolid, 128 mu g of RNA per mi produced an IC50 of 50 mu M whereas a concentration of 32 mu g/ml yielded an IC50 of 20 mu M. Investigating lower RNA template concentrations in linezolid inhibition experiments revealed that 32 and 8 mu g of MS2 phage RNA per mi produced IC(50)s of 24 and 15 mu M, respectively, This phenomenon was shared by the translation initiation inhibitor kasugamycin but not by streptomycin, Neither oxazolidinone inhibited the formation of N-formylmethionyl-tRNA, elongation, or termination reactions of bacterial translation. The oxazolidinones appear to inhibit bacterial translation at the initiation phase of protein synthesis.