Sun Rui, Cui Yueting, Wu Yining, Gao Meng, Xue Shiyuan, Li Ruibin, Zboril Radek, Zhang Chengdong
School of Environment, Beijing Normal University, 19 Xinjiekouwai Street, Haidian District, Beijing 100875, China.
State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, China.
ACS Nano. 2025 Jan 14;19(1):1702-1712. doi: 10.1021/acsnano.4c15607. Epub 2024 Dec 31.
The rapid spread of antimicrobial resistance poses a critical threat to global health and the environment. Antimicrobial nanomaterials, including silver nanoparticles (AgNPs), are being explored as innovative solutions; however, the emergence of nanoresistance challenges their effectiveness. Understanding resistance mechanisms is essential for developing antievolutionary strategies. AgNPs exhibit diverse resistance mechanisms, and our findings reveal a dynamic transition between these mechanisms: from flagellin-mediated AgNP precipitation (state I) to activation of the copper efflux pump (CusCFBA) system (state II). We designed targeted physicochemical interventions to counteract these mechanisms. Energy supply blocking was effective for state I, while for state II, neutralizing intracellular acidic pH significantly reduced resistance. These strategies reduced nanoresistance/tolerance by up to 10,000-fold. Additionally, resistance evolution can be completely halted by disrupting the energy supply using carbonyl cyanide 3-chlorophenylhydrazone and overactivating sigma E, one of the key envelope stress regulators that govern resistance transitions. Our findings provide practical strategies to overcome nanoresistance, offering a groundbreaking approach to enhance nanoantimicrobials' efficacy in medical therapies and combat resistance evolution.
抗菌耐药性的迅速传播对全球健康和环境构成了严重威胁。包括银纳米颗粒(AgNPs)在内的抗菌纳米材料正在作为创新解决方案进行探索;然而,纳米耐药性的出现对其有效性提出了挑战。了解耐药机制对于制定抗进化策略至关重要。AgNPs表现出多种耐药机制,我们的研究结果揭示了这些机制之间的动态转变:从鞭毛蛋白介导的AgNP沉淀(状态I)到铜外排泵(CusCFBA)系统的激活(状态II)。我们设计了有针对性的物理化学干预措施来对抗这些机制。能量供应阻断对状态I有效,而对于状态II,中和细胞内酸性pH值可显著降低耐药性。这些策略将纳米耐药性/耐受性降低了多达10000倍。此外,通过使用羰基氰化物3-氯苯腙破坏能量供应并过度激活σE(一种控制耐药性转变的关键包膜应激调节因子),可以完全阻止耐药性的进化。我们的研究结果提供了克服纳米耐药性的实用策略,为提高纳米抗菌剂在医学治疗中的疗效和对抗耐药性进化提供了一种开创性的方法。
Nat Nanotechnol. 2017-12-4
ACS Appl Mater Interfaces. 2021-8-11