肺炎支原体外排泵ABC Transporter在大环内酯类耐药中的作用机制研究

项目名称： 肺炎支原体外排泵ABC Transporter在大环内酯类耐药中的作用机制研究

项目编号： No.81672062

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 孙红妹

作者单位： 首都儿科研究所

项目金额： 25万元

中文摘要： 目前Mp耐药机制研究主要局限于23S rRNA基因点突变。项目组前期在Mp全基因组测序分析中发现Mp耐药株与敏感株的差异SNPs富集于外排泵系统ABC Transporter基因区，并实验证实外排泵抑制剂可显著降低耐药株MIC值，推测ABC Transporter可能在Mp大环内酯类耐药中发挥作用。本研究拟采用同源重组方法构建ABC Transporter基因突变株和ABC Transporter基因与23S rRNA基因同时突变菌株，检测两者耐药性差异，并以标准株做对照，了解ABC Transporter基因突变与菌株耐药及原有23SrRNA基因突变相关性；检测临床标本ABC Transporter基因，探讨其在临床耐药性中的作用，为进一步阐明Mp耐药机制，开辟Mp新的治疗靶点和药物提供新思路。

中文关键词： 肺炎支原体；抗药性；外排泵；ABC；转座子；基因突变

英文摘要： The mutations on 23S ribosomal RNA gene were known to be the major mechanism that gives rise to the macrolide resistance in M.pneumoniae, It is important to find new resistant mechanism. In our previous study, more new SNPs were found focus on ABC Transporter genes by using whole genome sequencing method, and efflux pump inhibitor could reduce the MIC values of macrolide resistant MP, it was speculated that SNPs in ABC Transporter genes may play a great role in M. pneumoniae drug resistance. In this study, we will construct the ABC Transporter gene mutation strains and ABC Transporter gene combined with 23S ribosomal RNA gene mutations strains, observe their macrolide resistance and compare with reference strains, to identify the mechanism of the ABC Transporter genes in M. pneumoniae resistance and explore the relationship between ABC Transporter gene mutations and 23S rRNA mutations. Combining with the clinical data, the SNPs of ABC Transporter genes were detected in clinical specimens for the further research of the role of ABC Transporter genes in M. pneumoniae macrolide resistance.

英文关键词： Mycoplasma pneumoniae;drug resistance; efflux pump;ABC Tansportor;gene mutation