Stable peptide-assembled nanozyme mimicking dual antifungal actions

Ye Yuan, Lei Chen, Kexu Song, Miaomiao Cheng, Ling Fang, Lingfei Kong, Lanlan Yu, Ruonan Wang, Zhendong Fu, Minmin Sun, Qian Wang, Chengjun Cui, Haojue Wang, Jiuyang He, Xiaonan Wang, Yuan Liu, Bing Jiang, Jing Jiang, Chenxuan Wang, Xiyun Yan, Xinzheng Zhang and Lizeng Gao ()
Additional contact information
Ye Yuan: Zhengzhou University
Lei Chen: Chinese Academy of Sciences
Kexu Song: Zhengzhou University
Miaomiao Cheng: Zhengzhou University
Ling Fang: Chinese Academy of Sciences
Lingfei Kong: Chinese Academy of Sciences
Lanlan Yu: School of Basic Medicine Peking Union Medical College
Ruonan Wang: School of Basic Medicine Peking Union Medical College
Zhendong Fu: Chinese Academy of Sciences
Minmin Sun: Chinese Academy of Sciences
Qian Wang: Chinese Academy of Sciences
Chengjun Cui: Wuxi Branch of Zhongda Hospital Southeast University
Haojue Wang: Wuxi Branch of Zhongda Hospital Southeast University
Jiuyang He: Chinese Academy of Sciences
Xiaonan Wang: Chinese Academy of Sciences
Yuan Liu: Zhengzhou University
Bing Jiang: Zhengzhou University
Jing Jiang: Chinese Academy of Sciences
Chenxuan Wang: School of Basic Medicine Peking Union Medical College
Xiyun Yan: Zhengzhou University
Xinzheng Zhang: Chinese Academy of Sciences
Lizeng Gao: Zhengzhou University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Date: 2024
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DOI: 10.1038/s41467-024-50094-6

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