新德里金属β-内酰胺酶-1（NDM-1）在全世界范围内广泛流行，产酶菌可抵抗几乎所有类型的β-内酰胺类抗生素，是“超级细菌”事件的罪魁祸首。NDM-1是一种胞外酶，成熟后由产酶菌释放至胞外发挥水解作用。最新文献报道其释放过程依赖于细菌外膜囊泡（OMV）的载体运输功能，我们在前期工作中对这一结论进行验证，并发现添加细菌OMV抑制剂可显著降低产NDM-1菌株的耐药能力。因此我们提出科学问题：能否通过抑制细菌OMV分泌的方式显著降低“超级细菌”的耐药性以辅助临床治疗？其作用机制如何？为回答这一问题，我们将设计体内/体外实验观察抑制细菌OMV分泌对于“超级细菌”耐药性和生存性的影响，讨论这一辅助抗菌策略的作用效果和作用机制；随后尝试筛选细菌的关键OMV调控靶点，为高效抑制细菌OMV分泌打下基础。本项目另辟蹊径，探讨了一种新型辅助抗菌策略的应用价值和作用机制，为拓宽新型抗菌药物研发思路提供线索。

New Delhi Metallo-β-lactamase-1 (NDM-1) has been widely disseminated in recent years, the NDM-1 producing strains can hydrolyze almost all types of β-lactam antibiotics, and was responsible for the superbug incident. NDM-1 is an extracellular enzyme, which is released to extracellular space by NDM-1-producing bacteria. Recent literatures reported that the release process of NDM-1 depends on the carrier transport function of bacterial outer membrane vesicles (OMV). We validated this conclusion in previous work and found that bacterial OMV secretion inhibitor could significantly reduce the resistance of NDM-1-producing strains. We therefore ask the following questions: Can we attenuating the antimicribial aesistance and viability of NDM-1 producing strain by inhibiting it’s OMV secretion level? What is the mechanism of its action? To answer these questions, we will design in vivo / in vitro experiments to observe the effects of this antibacterial strategy, and we will also screen the new OMV regulatory proteins for inhibition the OMV secretion efficiently in future. This project explores a new type of auxiliary antibacterial strategy, provides a new idea for antimicrobial agents research.