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Antimicrobial Activity of an Fmoc-Plantaricin 149 Derivative Peptide against Multidrug-Resistant Bacteria

Gabriela Marinho Righetto1, José Luiz de Souza Lopes2, Paulo José Martins Bispo3

  • 1Laboratory of Molecular Epidemiology and Microbiology, Department of Physics and Interdisciplinary Science, São Carlos Institute of Physics, University of São Paulo, São Carlos 13563-120, Brazil.

Antibiotics (Basel, Switzerland)
|February 25, 2023
PubMed

Insights

A novel antimicrobial peptide, Pln149-PEP20, shows potent bactericidal activity against multidrug-resistant bacteria. This peptide likely targets bacterial membranes, offering a promising new therapeutic avenue for combating antimicrobial resistance.

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Antimicrobial resistance (AMR) is a significant global health threat.
  • Novel antimicrobial agents are urgently needed to combat multidrug-resistant (MDR) bacteria.
  • Antimicrobial peptides (AMPs) are being investigated as potential therapeutics against resistant infections.

Purpose of the Study:

  • To design and characterize a novel analog of the antimicrobial peptide Plantaricin 149 (Pln149-PEP20).
  • To evaluate the antimicrobial activity and resistance development potential of Pln149-PEP20.
  • To elucidate the mechanism of action of Pln149-PEP20 against bacteria.

Main Methods:

  • Minimal inhibitory concentrations (MICs) determination for 60 bacterial strains.
  • In vitro directed-evolution experiment to assess resistance development.
  • Whole-genome sequencing of resistant mutants.
  • Synchrotron radiation circular dichroism, membrane depolarization, and transmission electron microscopy (TEM) assays.

Main Results:

  • Pln149-PEP20 exhibited potent bactericidal activity against Gram-positive and Gram-negative bacteria, with MICs ranging from 1 to 512 mg/L.
  • Most mutations in resistant mutants were found in genes related to membrane metabolism.
  • Pln149-PEP20 was shown to disturb bacterial membranes, suggesting a carpet-like mechanism of action.

Conclusions:

  • Pln149-PEP20 demonstrates significant potential as a novel antimicrobial therapeutic.
  • The peptide's primary mechanism involves disruption of bacterial membranes.
  • Further optimization of Pln149-PEP20 may lead to effective treatments for resistant bacterial infections.
Keywords:
Plantaricin 149carpet-like mechanismsynergism

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