The decline of clinically effective antibiotics has made it necessary to develop more effective antimicrobial agents, especially for refractory biofilm-related infections. Silver nanoparticles (AgNPs) are a new type of antimicrobial agent that can eradicate biofilms and reduce bacterial resistance, but its anti-biofilm mechanism has not been elucidated. In this study, we investigated the molecular mechanism of AgNPs against multidrug-resistant Pseudomonas aeruginosa by means of anti-biofilm tests, scanning electron microscopy (SEM), and tandem mass tag (TMT)-labeled quantitative proteomics. The results of anti-biofilm tests demonstrated that AgNPs inhibited the formation of P. aeruginosa biofilm and disrupted its preformed biofilm. SEM showed that when exposed to AgNPs, the structure of the P. aeruginosa biofilm was destroyed, along with significant reduction of its biomass. TMT-labeled quantitative proteomic analysis revealed that AgNPs could defeat the P. aeruginosa biofilm in multiple ways by inhibiting its adhesion and motility, stimulating strong oxidative stress response, destroying iron homeostasis, blocking aerobic and anaerobic respiration, and affecting quorum sensing systems. Our findings offer a new insight into clarifying the mechanism of AgNPs against biofilms, thus providing a theoretical basis for its clinical application.

中文翻译：

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定量蛋白质组学揭示了银纳米颗粒对抗多药耐药的铜绿假单胞菌生物膜的机制。

临床上有效的抗生素的下降使得必须开发更有效的抗菌剂，尤其是对于难治性生物膜相关感染。银纳米颗粒（AgNPs）是一种新型的抗菌剂，可以消灭生物膜并降低细菌的抵抗力，但其抗生物膜的作用机理尚未阐明。在这项研究中，我们通过抗生物膜试验，扫描电子显微镜（SEM）和串联质量标签（TMT）标记的定量蛋白质组学研究了AgNPs对抗多药耐药的铜绿假单胞菌的分子机制。抗生物膜试验的结果表明，AgNPs抑制了铜绿假单胞菌的形成。生物膜并破坏了其预制的生物膜。SEM显示，暴露于AgNPs时，铜绿假单胞菌生物膜的结构被破坏，其生物量显着减少。TMT标记的定量蛋白质组分析表明，AgNPs可以通过抑制铜绿假单胞菌的粘附和运动，刺激强烈的氧化应激反应，破坏铁稳态，阻断有氧和无氧呼吸以及影响群体感应系统，以多种方式击败铜绿假单胞菌生物膜。我们的发现为阐明AgNPs对抗生物膜的机制提供了新的见识，从而为其临床应用提供了理论基础。