To eliminate multidrug-resistant bacteria of Acinetobacter baumannii, we screened 1100 Food and Drug Administration–approved small molecule drugs and accessed the broxyquinoline (Bq) efficacy in combination with various metal ions. Antibacterial tests demonstrated that the prepared Zn(Bq)₂ complex showed ultralow minimum inhibitory concentration of ~0.21 micrograms per milliliter with no resistance after 30 passages. We then constructed the nano zeolitic imidazolate framework-8 (ZIF-8) as a drug carrier of Zn(Bq)₂ and also incorporated the photosensitizer chlorin e6 (Ce6) to trace and boost the antibacterial effect. To further ensure the stable and targeted delivery, we genetically engineered outer membrane vesicles (OMVs) with the ability to selectively target A. baumannii. By coating the ZnBq/Ce6@ZIF-8 core with these OMV, the resulted drug (ZnBq/Ce6@ZIF-8@OMV) exhibited exceptional killing efficacy (>99.9999999%) of A. baumannii. In addition, in vitro and in vivo tests were also respectively carried out to inspect the remarkable efficacy of this previously unknown nanodrug in eradicating A. baumannii infections, including biofilms and meningitis.

中文翻译：

---

增压精准杀手：针对鲍曼不动杆菌筛选金属抗生素的基因工程仿生药物

为了消除鲍曼不动杆菌的多重耐药菌，我们筛选了1100种FDA批准的小分子药物，并评估了溴喹啉（Bq）与各种金属离子结合的疗效。抗菌测试表明，制备的Zn(Bq) ₂配合物具有超低的最低抑菌浓度，约为0.21微克/毫升，传代30次后无耐药性。然后，我们构建了纳米沸石咪唑骨架-8（ZIF-8）作为Zn(Bq) ₂的药物载体，并掺入光敏剂二氢卟酚e6（Ce6）来跟踪和增强抗菌效果。为了进一步确保稳定和有针对性的递送，我们对外膜囊泡（OMV）进行了基因改造，使其能够选择性地靶向鲍曼不动杆菌。通过用这些 OMV 包覆 ZnBq/Ce6@ZIF-8 核心，所得药物 (ZnBq/Ce6@ZIF-8@OMV) 对鲍曼不动杆菌表现出卓越的杀灭功效 (>99.9999999%) 。此外，还分别进行了体外和体内测试，以检验这种以前未知的纳米药物在根除鲍曼不动杆菌感染（包括生物膜和脑膜炎）方面的显着功效。