近期，NDM-1酶在河南地区肠杆菌科细菌中出现高度流行和跨种属传播，导致了不同种属XDR菌株的产生，给临床治疗带来了极大困难。质粒是介导blaNDM-1播散的重要工具。我们前期在1株XDR 阴沟肠杆菌中发现了一个不相容性未知的新型NDM-1质粒，该质粒可通过接合转移使全敏感的E. coli J53变成XDR菌株。另外，1株XDR奇异变形杆菌在携带类似质粒的同时还携带沙门氏菌基因岛1的新变异体（SGI1-Z），结合最新报道的携带blaNDM-1的奇异变形杆菌基因岛1（PGI1），我们推测结构多变的可移动元件SGI1/PGI1将在介导blaNDM-1传播中发挥重要作用。本项目拟通过全质粒测序分析和适应性代价研究探讨新型NDM质粒的进化过程和播散稳定性；同时探查SGI1/PGI1在奇异变形杆菌中的流行，通过结构解析和可转移性分析，探讨该类元件在介导blaNDM-1传播和XDR菌株产生中的作用。

The sporadic emergence of New Delhi metallo-β-lactamase 1 (NDM-1) producing Enterobacteriaceae in mainland China has been reported increasingly since 2013. Unexpectedly, the prevalence and active spread of blaNDM-1 in Enterobacteriaceae was observed in Henan province, leading to the emergence of extensively drug-resistant (XDR) isolates, presents an urgent threat to human health.Given that the blaNDM-1 gene is located mostly on conjugative plasmids and always associated with other antibiotic resistance determinants, the acquisition of conjugative plasmids co-harboring blaNDM-1 and multiple resistance genes in clinical Enterobacteriaceae isolates may lead to the emergence of XDR strains and seriously limit the therapeutic options. Our recent study demonstrated that a pan-susceptible Escherichia coli J53 became an XDR strain susceptible only to tigecycline and colistin after accepting a self-transferable NDM-1 plasmid from a clinical XDR isolate of Enterobacter cloacae via conjugation under the laboratory conditions. This self-transferable plasmid of ca.360 kb is unique, which co-harboring multiple resistance determinants including blaNDM-1, fosA3 and armA, and may belong to a novel incompatibility group. In order to characterize the novel conjugative plasmid, the whole sequence analysis and fitness cost assay will be conducted to illuminate the structure, evolution and capability for dissemination of resistance genes of this plasmid. Moreover, a novel variant of Salmonella genomic island 1 (SGI1-Z) carrying multiple resistance genes was identified in an XDR Proteus mirabilis which harbored a similar conjugative NDM-1 plasmid, this finding together with a recent report of the emergence of a novel SGI1 variant, named PGI1 (Proteus genomic island 1) carrying blaNDM-1 in a P. mirabilis clinical isolate, indicating the integrative mobilizable elements of SGI1/PGI1 may play an important role in dissemination resistance genes including blaNDM-1. Thus, we plan to evaluate the prevalence, molecular characterization and mobility of SGI1/PGI1 in carbapenem-resistant P. mirabilis to highlight the potential role of these elements in spread of resistance determinants.