Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea.
Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea.
Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.02752-16. Print 2017 Sep.
is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the , intracellular, and activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several strains and in a macrophage model of infection. In the murine model, a similar efficacy to linezolid was achieved, especially in the lungs. We induced laboratory-generated resistance to LCB01-0371; sequencing analysis revealed mutations in of T424C and G419A and a nucleotide insertion at the 503 position. Furthermore, LCB01-0371 inhibited the growth of amikacin-, cefoxitin-, and clarithromycin-resistant strains. Collectively, our data indicate that LCB01-0371 might represent a promising new class of oxazolidinones with improved safety, which may replace linezolid for the treatment of .
是一种高致病性耐药快速生长分枝杆菌。在这项研究中，我们评估了新型安全的恶唑烷酮衍生物 LCB01-0371 治疗 感染的细胞内和细胞外活性，并比较了其耐药性与其他恶唑烷酮药物的耐药性。LCB01-0371 对几种 株有效，并且在感染的巨噬细胞模型中有效。在小鼠模型中，与利奈唑胺的疗效相似，特别是在肺部。我们诱导了对 LCB01-0371 的实验室产生的耐药性；测序分析显示 T424C 和 G419A 的 424 位 T424C 和 G419A 突变以及 503 位的核苷酸插入。此外，LCB01-0371 抑制了阿米卡星、头孢西丁和克拉霉素耐药株的生长。总之，我们的数据表明，LCB01-0371 可能代表一类具有改善安全性的有前途的新型恶唑烷酮类药物，可替代利奈唑胺治疗 。
