生物膜
流出
群体感应
微生物学
多重耐药
光敏剂
金黄色葡萄球菌
抗生素耐药性
聚糖
抗菌剂
抗药性
耐甲氧西林金黄色葡萄球菌
生物
抗生素
细菌
化学
生物化学
糖蛋白
遗传学
有机化学
作者
Feng‐Wei Xia,Bin Guo,Yu Zhao,Jiali Wang,Yuan Chen,Pan Xiu,Xin Li,Jia‐Xing Song,Yu Wan,Shun Feng,Mingyu Wu
标识
DOI:10.1002/adma.202309797
摘要
Stubborn biofilm infections pose serious threats to human health due to the persistence, recurrence, and dramatically magnified antibiotic resistance. Photodynamic therapy has emerged as a promising approach to combat biofilm. Nevertheless, how to inhibit the bacterial signal transduction system and the efflux pump to conquer biofilm recurrence and resistance remains a challenging and unaddressed issue. Herein, a boric acid-functionalized lipophilic cationic type I photosensitizer, ACR-DMP, is developed, which efficiently generates •OH to overcome the hypoxic microenvironment and photodynamically eradicates methicillin-resistant Staphylococcus aureus (MRSA) and biofilms. Furthermore, it not only alters membrane potential homeostasis and osmotic pressure balance due to its strong binding ability with plasma membrane but also inhibits quorum sensing and the two-component system, reduces virulence factors, and regulates the activity of the drug efflux pump attributed to the glycan-targeting ability, helping to prevent biofilm recurrence and conquer biofilm resistance. In vivo, ACR-DMP successfully obliterates MRSA biofilms attached to implanted medical catheters, alleviates inflammation, and promotes vascularization, thereby combating infections and accelerating wound healing. This work not only provides an efficient strategy to combat stubborn biofilm infections and bacterial multidrug resistance but also offers systematic guidance for the rational design of next-generation advanced antimicrobial materials.
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