vanM型万古霉素耐药肠球菌（VRE）自2010年首次报道以来，已在我国多地及新加坡出现并逐渐增多，值得关注。部分异质性耐药vanM型VRE耐药表型隐匿，常规方法无法准确判断其耐药性，易延误临床诊治及防控，其危害不容忽视。本课题针对此类耐药株万古霉素诱导前后可出现耐药基因串联复制、拷贝增加，以及耐药性升高这一现象；并根据其他细菌中已有研究显示，SOS应答可通过RecA及IS形成基因串联复制介导细菌耐药水平升高，推测vanM型VRE异质性耐药株由SOS应答激发，RecA及IS共同参与的vanM基因串联复制可导致高水平耐药。本课题拟通过大范围菌株收集、耐药表型与基因型分析，明确异质性耐药vanM型VRE分布；通过RecA 及IS转座酶基因敲除、回补明确相关基因在vanM基因串联复制及耐药性上升中的作用；并采用环丙沙星等药物激发细菌SOS反应，进一步明确SOS反应在细菌耐药基因串联复制中的作用。

Since the first report of the vanM type Vancomycin resistant Enterococcus (VRE) in 2010, it has appeared in many areas of China and in Singapore. Some heterogeneous vancomycin-resistant vanM VRE phenotype is concealed. Conventional methods can not accurately determine their resistance, which is easy to delay clinical diagnosis and treatment, and its harm can not be ignored. In this project, we aimed at the phenomena of tandem replication, increased gene copy and increased drug resistance of vancomycin-resistant strains after vancomycin induction; and SOS response resulting the increase of bacterial resistance level through RecA and IS mediated tandem replication. It is speculated that vanM VRE heterogeneous drug-resistant strains are stimulated by SOS response, and the tandem replication of vanM genes involving RecA and IS can lead to high level of drug resistance. This project through the analysis of a wide range of strain's resistant phenotype and genotype to clear heterogeneous resistance type vanM VRE distribution; through gene knockout and compensation of RecA and IS transposase genes to identification of the role of related genes in vanM gene tandem replication and drug resistance; and the use of ciprofloxacin and other drugs to stimulate bacterial SOS reaction, and further clarify the role of SOS reaction in tandem replication of bacterial resistance genes.