Chiral Nanoclusters as Alternative Therapeutic Strategies to Confront the Health Threat from Antibiotic-Resistant Pathogens

文献类型： 外文期刊

第一作者： Wang, Zhe

作者： Wang, Zhe;Tian, Yijin;Hao, Jinghua;Liu, Ya;Tang, Jie;Liu, Yin;Zhu, Nali;Li, Zhigang;Li, Lingxiangyu;Wang, Zhe;Tian, Yijin;Hao, Jinghua;Tang, Jie;Hu, Ligang;Wang, Yawei;Jiang, Guibin;Wang, Zhe;Tian, Yijin;Hao, Jinghua;Tang, Jie;Xu, Zhenlan;Tang, Biao;Huang, Xiu;Huang, Xiu

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关键词： Antibacterial activity; chiral silver nanoclusters; antimicrobial resistance; cytocompatibility; Pseudomonas aeruginosa

期刊名称：ACS NANO （ 影响因子：17.1； 五年影响因子：17.1 ）

ISSN： 1936-0851

年卷期： 2024 年 18 卷 9 期

页码：

收录情况： SCI

摘要： Pseudomonas aeruginosa (P. aeruginosa), a drug-resistant Gram-negative pathogen, is listed among the "critical" group of pathogens by the World Health Organization urgently needing efficacious antibiotics in the clinics. Nanomaterials especially silver nanoparticles (AgNPs) due to the broad-spectrum antimicrobial activity are tested in antimicrobial therapeutic applications. Pathogens rapidly develop resistance to AgNPs; however, the health threat from antibiotic-resistant pathogens remains challenging. Here we present a strategy to prevent bacterial resistance to silver nanomaterials through imparting chirality to silver nanoclusters (AgNCs). Nonchiral AgNCs with high efficacy against P. aeruginosa causes heritable resistance, as indicated by a 5.4-fold increase in the minimum inhibitory concentration (MIC) after 9 repeated passages. Whole-genome sequencing identifies a Rhs mutation related to the wall of Gram-negative bacteria that possibly causes morphology changes in resistance compared to susceptible P. aeruginosa. Nevertheless, AgNCs with laevorotary chirality (l-AgNCs) induce negligible resistance even after 40 repeated passages and maintain a superior antibacterial efficiency at the MIC. l-AgNCs also show high cytocompatibility; negligible cytotoxicity to mammalian cells including JB6, H460, HEK293, and RAW264.7 is observed even at 30-fold MIC. l-AgNCs thus are examined as an alternative to levofloxacin in vivo, healing wound infections of P. aeruginosa efficaciously. This work provides a potential opportunity to confront the rising threat of antimicrobial resistance by developing chiral nanoclusters.

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