中国防痨杂志2017，Vol.39Issue(4)：397-401,5.DOI:10.3969/j.issn.1000-6621.2017.04.017
体外诱导获取对利奈唑胺耐药的结核分枝杆菌菌株及其稳定性研究
Induction in vitro and stability of Mycobacterium tuberculosis resistance to Linezolid
摘要
Abstract
Objective To gain strains of Mycobacterium tuberculosis (MTB) resistance with Linezolid (Lzd) utilizing twice increasing concentration induction in vitro,investigating its stability of drug resistance and using which to screen for anti-tuberculosis (anti-TB) activity of new compounds.Methods MTB standard strains H37Rv (ATCC27294) were sub-cultured on solid culture medium containing twice increasing concentration of Lzd and induced the drug resistance to Lzd.The minimal inhibitory concentrations (MIC) of partial anti-TB drugs against induced drug resistant strains in vitro were detected through micro-plate alamar blue assay (MABA),rplC genes of drug resistant strains obtained from induction in vitro were sequenced and identified for mutations.Induced drug resistant strains were continuously subcultured 10 generations on solid medium without drug to observe the resistance stability,including varieties of MIC and rplC gene mutations.Results Seven MTB monoclonal strains were obtained after induction with the MTB standard strains,the ranges of MIC values of Lzd against these strains were 5.99-18.28 μg/ml,which were eight times higher than before (0.25 μg/ml),drug resistant strains were successfully acquired and were resistant to Sutezolid (PNU-100480) simultaneously.T460C mutation in gene rplC was detected in all 7 strains by sequencing.After 10 serially generations on solid culture medium without drug,MIC values of induced drug resistant strains were slightly declined (4.71-7.47 μg/ml),but all were stable for more than eight times than before.Conclusion MTB strains resistant to two kinds of Oxazolidinones antibiotic were obtained by induction in vitro.Mutation of rplC gene was related to Oxazolidinones antibiotic drug resistance of MTB.Drug resistant stability of MTB to Oxazolidinones antibiotic was strong,and it is difficult for MTB to resume susceptibility.关键词
分枝杆菌,结核/恶唑烷酮类/体外研究/抗药性,细菌/连续传代Key words
Mycobacterium tuberculosis/Oxazolidinones/In vitro/Drug resistance, bacterial/Serial passage引用本文复制引用
胡明豪,王彬,付雷,徐建,陆宇..体外诱导获取对利奈唑胺耐药的结核分枝杆菌菌株及其稳定性研究[J].中国防痨杂志,2017,39(4):397-401,5.基金项目
“十二五”国家科技重大专项(2015ZX09102007-015) （2015ZX09102007-015）
北京市医院管理局“登峰”计划(DFL20151501) （DFL20151501）
