2. Academic Validation
  3. LL-37-derived peptide shows promising antimicrobial potential against multidrug-resistance pathogens

LL-37-derived peptide shows promising antimicrobial potential against multidrug-resistance pathogens

  • Eur J Med Chem. 2026 Feb 15:304:118547. doi: 10.1016/j.ejmech.2025.118547.
Demeke Asmamaw 1,  Huajun Cai 2,  Prateeksha Prateeksha 3,  Mehwish Khalid 1,  James Mwangi 1,  Wang Yi 4,  Quimin Lu 5,  Ren Lai 6,  Zilei Duan 7
Affiliations

Affiliations

  • 1 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan, 650201, China; Kunming College of Life Science, University of Academy of Sciences, Kunming, 650204, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan, 650201, China; Kunming College of Life Science, University of Academy of Sciences, Kunming, 650204, China; University of Chinese Academy of Sciences, Beijing, 100049, China; School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
  • 3 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan, 650201, China.
  • 4 Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou, 511458, China.
  • 5 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan, 650201, China; Kunming College of Life Science, University of Academy of Sciences, Kunming, 650204, China; Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Yunnan, 650106, China.
  • 6 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan, 650201, China; Kunming College of Life Science, University of Academy of Sciences, Kunming, 650204, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: [email protected].
  • 7 Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), State Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, The Chinese Academy of Sciences, No.17 Longxin Road, Kunming, Yunnan, 650201, China; Kunming College of Life Science, University of Academy of Sciences, Kunming, 650204, China. Electronic address: [email protected].
PMID: 41485275 DOI: 10.1016/j.ejmech.2025.118547
Abstract

The increasing prevalence of multidrug-resistant (MDR) Bacterial infections poses global health challenges, highlighting the urgent need for new antimicrobial agents. The key advantages of antimicrobial peptides are their ability to rapid bactericidal activity and their low propensity for resistance development. In this study, we designed a series of antimicrobial peptides by fusing the two fragments of antimicrobial peptides Cathelicidin-BF (1-9) and LL-37 (17-29), and then tested against selected Gram-negative and Gram-positive Bacterial strains. Among these peptides, KF-22 displayed potent Antibacterial activity against a panel of Gram-negative and Gram-positive pathogens with MICs less than 5 μg/mL, with demonstrating low toxicity. Moreover, KF-22 exhibits rapid bactericidal activity and a low propensity to induce resistance, simultaneously showing excellent anti-biofilm and persisters activity. Mechanistic studies revealed that KF-22 induces membrane damage by targeting bacterial-specific membrane components, leading to the dissipate the proton motive force (PMF) and resulting in metabolic perturbations. Furthermore, in mice models no significant change was observed in plasma biochemical parameters between the treated and the control groups. In addition, in vivo studies confirmed that KF-22 are effective against drug-resistant pathogens. Taken together, the findings suggest that KF-22 is a promising candidate for further development to tackle MDR Bacterial infections.

Keywords

Antimicrobial peptide; Bacterial membrane; Efficacy; Fragment fusion; Multidrug-resistant.

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