An antimicrobial peptide as a potential therapy for bacterial pneumonia that alleviates antimicrobial resistance

Chao Zhong, Yongtao He, Jing Zou, Luyang Gao, Jiahui Wang, Jingyi Zhu, Wenjing Xue, Sanhu Gou, Yun Zhang, Hui Liu and Jingman Ni ()
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Chao Zhong: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Yongtao He: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Jing Zou: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Luyang Gao: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Jiahui Wang: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Jingyi Zhu: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Wenjing Xue: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Sanhu Gou: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Yun Zhang: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Hui Liu: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066
Jingman Ni: Lanzhou University, Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: Abstract Bacterial pneumonia remains a global health threat that is worsened by drug-resistant bacteria, underscoring the need for the development of new antimicrobial agents. Antimicrobial peptides are promising new candidates with broad-spectrum activity and low potential for resistance development. Here, we report a linear antimicrobial peptide (AMP) that consists of four repeating units of (D-tryptophan)-(D-arginine)-(D-lysine). This peptide exhibits high stability and robust antimicrobial activity against multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and Klebsiella pneumoniae, and improved biocompatibility. Furthermore, the AMP shows low potential for resistance development and the ability to alleviate resistance and restore antibiotic sensitivity due to multiple mechanisms, including membrane targeting and non-membrane lysis (DNA binding, reactive oxygen species accumulation, ATP depletion, metabolic interference). In vivo, the peptide showed promising therapeutic efficacy in a model of methicillin-resistant Staphylococcus aureus and K. pneumoniae pneumonia, as well as in a lipopolysaccharide-induced lung injury model.

Date: 2025
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DOI: 10.1038/s41467-025-65449-w

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