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

Demeke Asmamaw1, Huajun Cai2, Prateeksha Prateeksha3

  • 1Engineering 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.

Insights

A novel antimicrobial peptide, KF-22, shows potent activity against multidrug-resistant bacteria. This peptide demonstrates rapid killing, low resistance development, and anti-biofilm properties, offering a promising new therapeutic candidate.

Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • Multidrug-resistant (MDR) bacterial infections are a growing global health threat.
  • New antimicrobial agents are urgently needed to combat resistant pathogens.
  • Antimicrobial peptides (AMPs) offer rapid bactericidal activity and low resistance potential.

Purpose of the Study:

  • To design and evaluate novel antimicrobial peptides derived from Cathelicidin-BF and LL-37 fragments.
  • To assess the antibacterial efficacy, toxicity, and resistance potential of the designed peptides.
  • To investigate the mechanism of action and in vivo effectiveness of the lead candidate peptide.

Main Methods:

  • Fusion of Cathelicidin-BF (1-9) and LL-37 (17-29) fragments to create novel antimicrobial peptides.
  • In vitro testing against Gram-negative and Gram-positive bacterial strains to determine Minimum Inhibitory Concentrations (MICs).
  • Assessment of cytotoxicity, anti-biofilm activity, persister cell activity, mechanism of action (membrane damage, proton motive force dissipation), and in vivo efficacy in mouse models.

Main Results:

  • KF-22 demonstrated potent antibacterial activity against a range of pathogens, with MICs < 5 μg/mL.
  • KF-22 exhibited low toxicity, rapid bactericidal effects, and a low propensity for resistance development.
  • Mechanistic studies indicated KF-22 targets bacterial membranes, dissipates proton motive force, and shows anti-biofilm and anti-persister activity.
  • In vivo studies confirmed KF-22's effectiveness against drug-resistant pathogens with no observed significant toxicity in mice.

Conclusions:

  • KF-22 is a potent antimicrobial peptide with broad-spectrum activity against Gram-negative and Gram-positive bacteria.
  • KF-22 displays favorable properties including low toxicity, rapid action, and anti-resistance potential.
  • KF-22 represents a promising therapeutic candidate for combating multidrug-resistant bacterial infections.

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