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

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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
    Jinan University, State Key Laboratory of Bioactive Molecules and Druggability Assessment
    State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology)

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.

Suggested Citation

  • Chao Zhong & Yongtao He & Jing Zou & Luyang Gao & Jiahui Wang & Jingyi Zhu & Wenjing Xue & Sanhu Gou & Yun Zhang & Hui Liu & Jingman Ni, 2025. "An antimicrobial peptide as a potential therapy for bacterial pneumonia that alleviates antimicrobial resistance," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65449-w
    DOI: 10.1038/s41467-025-65449-w
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