产bla_(NDM-1)肺炎克雷伯菌的高水平多黏菌素耐药株制备及耐药机制研究  

High level polymyxin resistantisolates induced by colistin in bla_(NDM-1) carrying K.pneumoniae and study of the resistance mechanisms

作　　者：梁振伟 胡辛欣 聂彤颖 卢曦 李雪 王秀坤 杨信怡 李聪然 游雪甫 Liang Zhen-wei;Hu Xin-xin;Nie Tong-ying;Lu Xi;Li Xue;Wang Xiu-kun;Yang Xin-yi;Li Cong-ran;You Xue-fu(Beijing Key Laboratory of Antimicrobial Agents,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050)

机构地区：[1]中国医学科学院医药生物技术研究所抗感染药物研究北京市重点实验室,北京100050

出　　处：《中国抗生素杂志》2021年第9期873-878,共6页Chinese Journal of Antibiotics

基　　金：中国医学科学院医学与健康科技创新工程(No.2016-12M-3-014);“十三五”国家科技重大专项(No.2019ZX09721001);国家自然科学基金资助项目(No.81703399)。

摘　　要：目的研究产bla_(NDM-1)肺炎克雷伯菌产生多黏菌素耐药的可能性,并对相关机制进行分析。方法通过黏菌素肉汤传代培养研究携带bla_(NDM-1)菌株产生多黏菌素耐药的可能性,并对分离出的耐药株通过PCR、Real-time PCR、脉冲场凝胶电泳等方法进行耐药分子机制研究。结果通过黏菌素肉汤传代培养,产bla_(NDM-1)肺炎克雷伯菌可进一步表现高水平多黏菌素耐药表型。检测发现耐药株中膜孔蛋白基因及双组分调节系统中多黏菌素耐药相关基因发生表达水平变化,可能导致菌株对多黏菌素高水平耐药。结论产bla_(NDM-1)肺炎克雷伯菌经黏菌素传代诱导培养后可进一步发展多黏菌素耐药,需要引起临床注意。Objective To study the possibility of polymyxin resistance development in bla_(NDM-1)-carrying K.pneumoniae strains and to analyze the resistance mechanisms of the related isolates.Methods The possibility of polymyxin resistance development in bla_(NDM-1)-carryingstrains was studied by colistin induction in broth.Phenotypic analysis of drug resistance was performed by minimal inhibitory concentration(MIC)determination.The related mechanisms were explored by PCR,Real-time PCR and pulse-field gel electrophoresis analysis(PFGE).Results After colistin induction,the bla_(NDM-1)-carryingstrains demonstrated high level polymyxin resistance phenotype.Further mechanism explorations demonstrated the expression level changes of the membrane porin protein genes and the polymyxin resistance related two-component regulatory system genes in the related isolates,which are the possible reasons for the high level polymyxin resistance.Conclusion The bla_(NDM-1)-carrying K.pneumoniae canfurther develop polymyxin resistance by colistin induction in broth,which deserves attention in clinic.

关 键 词：肺炎克雷伯菌 bla_(NDM-1) 多黏菌素 诱导耐药 

分 类 号：R978.1[医药卫生—药品]