普鲁士蓝类似物抗生素增敏剂构建及应用
Construction and Application of Prussian Blue Analogue Antibiotic Sensitizers
李佳欣 1方舸2
作者信息
- 1. 苏州大学放射医学与辐射防护学院，苏州 215123
- 2. 苏州大学放射医学与辐射防护学院，苏州 215123;中国科学技术大学化学与材料科学学院，合肥 230026
- 折叠
摘要
研究目的：多重耐药革兰氏阴性菌传播及mcr-1耐药基因扩散，显著削弱多黏菌素的临床抗感染效能。亟需研发高效且安全的多黏菌素增敏策略，以提升对mcr-1介导耐药菌感染的防控能力。研究方法：本研究拟开发一种配位结构可调的银基普鲁士蓝类似物，并完成系统的理化表征；结合体外抗菌评价、生物膜抑制实验与耐药进化分析，探究该材料对多黏菌素 B 的增敏作用；进一步通过构建小鼠细菌性腹膜炎感染模型，系统评价其体内治疗效果，并深入揭示其协同抗菌的潜在机制。研究结果：本研究成功制备了两种银基普鲁士蓝类似物（AgPBsⅠ和AgPBsⅡ）。结果表明，AgPBsⅡ 展现出更卓越的多黏菌素 B 增敏效能。机制探究证实，AgPBsⅡ 不仅能协同破坏细菌细胞膜完整性，增加膜通透性，还能有效干扰细菌内部铁稳态，从而深度抑制生物膜的形成并显著延缓耐药表型的演化。在小鼠细菌性腹膜炎模型中，联合给药策略大幅降低了靶器官的细菌负荷，并有效缓解了感染引发的全身性炎症与组织损伤。研究结论： AgPBsⅡ 可通过"强化膜损伤-干扰铁稳态"的多维度协同机制，实现对多黏菌素 B 的高效增敏与抗耐药逆转。本研究为开发靶向细菌金属稳态的新型纳米抗菌增敏剂提供了极具潜力的设计思路。
Abstract
Research Objective: The transmission of multidrug-resistant Gram-negative bacteria and the spread of mcr-1 resistance genes have markedly weakened the clinical anti-infective efficacy of polymyxins. It is urgent to develop efficient and safe polymyxin sensitization strategies to improve the prevention and control of mcr-1-mediated resistant bacterial infections. Research Methods: This study designed silver-based Prussian blue analogs with adjustable coordination structures and performed systematic physicochemical characterization. Combined with in vitro antibacterial evaluation, biofilm inhibition experiments and drug resistance evolution analysis, the sensitizing effect of the materials on polymyxin B was explored. A mouse bacterial peritonitis model was further constructed to evaluate the in vivo therapeutic effect and reveal the potential synergistic antibacterial mechanism. Research Results: Two silver-based Prussian blue analogswere successfully prepared. With optimized coordination structure, AgPBs Ⅱ exhibited better polymyxin B sensitization performance. Mechanistic studies showed that AgPBs Ⅱ could synergistically damage bacterial membrane integrity, increase membrane permeability, interfere with bacterial iron homeostasis, inhibit biofilm formation and delay the evolution of drug-resistant phenotypes. In the mouse peritonitis model, combined administration reduced the bacterial load of target organs and alleviated systemic inflammation and tissue injury caused by infection. Research Conclusion: AgPBs Ⅱ achieves efficient polymyxin B sensitization and drug resistance reversal through the multi-dimensional synergistic mechanism of "enhanced membrane damage-interfered iron homeostasis". This study provides a promising design strategy for developing novel nano antibacterial sensitizers targeting bacterial metal homeostasis.关键词
普鲁士蓝类似物/多粘菌素B/mcr-1耐药菌/抗菌增敏剂/铁代谢Key words
Prussian blue analogs/Polymyxin B/mcr-1 drug-resistant bacteria/antibacterial sensitizer/iron metabolism引用本文复制引用
李佳欣,方舸.普鲁士蓝类似物抗生素增敏剂构建及应用[EB/OL].(2026-06-12)[2026-06-15].http://www.paper.edu.cn/releasepaper/content/202606-40.学科分类
医药卫生理论
