Synergistic wall digestion and cuproptosis against fungal infections using lywallzyme-induced self-assembly of metal-phenolic nanoflowers

Fang Liu, Yongcheng Chen, Yue Huang, Yutong Li, Zhouyu Lu, Haijie Han, Xiaohui Song (), Qiao Jin () and Jian Ji
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Fang Liu: Zhejiang University
Yongcheng Chen: Zhejiang University
Yue Huang: Zhejiang University
Yutong Li: Zhejiang University
Zhouyu Lu: Zhejiang University
Haijie Han: Zhejiang University
Xiaohui Song: Zhejiang University
Qiao Jin: Zhejiang University
Jian Ji: Zhejiang University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Fungi are very common infectious pathogens, which may cause invasive and potentially life-threatening infections. However, the efficacy of antifungal medications remains limited. Herein, a Cu2+-phenolic nanoflower is designed to combat fungal infections by combining cuproptosis and cell wall digestion. Firstly, protocatechuic acid (PA)-Cu2+ (PC) nanopetals are prepared by coordination interaction. Lywallzyme (Lyw) is then added to induce the self-assembly of PC to form Lyw loaded PC (PCW) nanoflowers. PCW nanoflowers can effectively adhere to fungal surface and Lyw can digest fungal cell walls to facilitate Cu2+ to penetrate into fungal interior, thereby exerting a synergistic fungicidal effect. PCW nanoflowers exhibit excellent fungicidal activity even in protein-rich and high-salt conditions, where dissociative Cu2+ completely loses fungicidal activity. Transcriptome sequencing analysis reveals that PCW can lead to fungal cuproptosis. The in vivo fungicidal effect of PCW nanoflowers is confirmed on a murine skin fungal infection model and a murine fungal keratitis model.

Date: 2024
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DOI: 10.1038/s41467-024-53410-2

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