万古霉素耐药肠球菌（VRE）主要由van基因簇造成，可编码多种功能蛋白导致万古霉素耐药。获得性van基因簇有8种，以vanA及vanB基因簇为主。国外已出现携带vanA基因的VVE菌株（具备万古霉素耐药性转换能力：万古霉素敏感菌转换为耐药菌）的局部爆发流行。近年来我国出现了携带新发现的vanM基因簇的屎肠球菌局部流行，我们在前期研究中首次发现了携带vanM基因的VVE菌株，可导致临床万古霉素治疗失败，但其确切机制仍不清。本研究将继续收集临床分离及肠道定植的肠球菌菌株，多重PCR法筛选van基因，结合药敏及诱导试验，获得VVE菌株，采用MLST分型阐明VVE主要流行克隆及克隆进化；采用转座子序列分析、全基因测序、质粒复制子分型等方法，阐明我国VVE菌株及van基因型分布，揭示VVE菌株万古霉素耐药性转换以及传播机制。为我国VVE菌株防控提供科学依据。

The van genes clusters are the main vancomycin resistance mechanism of vancomycin-resistant Enterococcus (VRE), which encode various functional proteins. A total of eight van gene clusters have been associated with acquired vancomycin resistance in enterococci,of which vanA and vanB clusters are dominant. Recently, outbreak of vancomycin susceptible enterococci containing vanA and capable of converting into a glycopeptide-resistant phenotype has been reported in aboard. Such strains were termed vancomycin-variable enterococci (VVE) due to this ability. In recent,the vanM clusters have been detected in China. The VVE isolates containing vanM were firstly found in our study, which have the ability of converting to vancomycin-resistant isolates causing the failure of vancomycin treatment.However, the mechansim is still unclear.In this study, we will continue to collect Enterococcus isolates in clinic and from intestinal colonization. The methods including multiplex PCR of van genes, susceptibility testing, vancomycin incubation experiment,PFGE and MLST, Whole-genome sequencing (WGS), plasmid replicon typing and so on, will be used to demonstrate the molecular mechanisms for in vivo switching into vancomycin resistance of VVE and horizontal spread of the van genes clusters. This study will supply the foundation of controlling VVE outbreak.