Supercharged precision killers: Genetically engineered biomimetic drugs of screened metalloantibiotics against <i>Acinetobacter baumanni</i>.

Abstract

To eliminate multidrug-resistant bacteria of <i>Acinetobacter baumannii</i>, 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 <i>A. baumannii</i>. 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 <i>A. baumannii</i>. 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 <i>A. baumannii</i> infections, including biofilms and meningitis.