Antimicrobial activity of an Fmoc-Plantaricin 149 derivative peptide against multidrug-resistant bacteria.
RIGHETTO, Gabriela Marinho; LOPES, José Luiz de Souza; BISPO, Paulo José Martins; ANDRÉ, Camille; SOUZA, Julia Medeiros; ANDRICOPULO, Adriano Defini; BELTRAMINI, Leila Maria; CAMARGO, Ilana Lopes Baratella da Cunha.
RIGHETTO, Gabriela Marinho; LOPES, José Luiz de Souza; BISPO, Paulo José Martins; ANDRÉ, Camille; SOUZA, Julia Medeiros; ANDRICOPULO, Adriano Defini; BELTRAMINI, Leila Maria; CAMARGO, Ilana Lopes Baratella da Cunha.
Abstract: Antimicrobial resistance poses a major threat to public health. Given the paucity of novel antimicrobials to treat resistant infections, the emergence of multidrug-resistant bacteria renewed interest in antimicrobial peptides as potential therapeutics. This study designed a new analog of the antimicrobial peptide Plantaricin 149 (Pln149-PEP20) based on previous Fmoc-peptides. The minimal inhibitory concentrations of Pln149-PEP20 were determined for 60 bacteria of different species and resistance profiles, ranging from 1 mg/L to 128 mg/L for Gram-positive bacteria and 16 to 512 mg/L for Gram-negative. Furthermore, Pln149-PEP20 demonstrated excellent bactericidal activity within one hour. To determine the propensity to develop resistance to Pln149-PEP20, a directed-evolution in vitro experiment was performed. Whole-genome sequencing of selected mutants with increased MICs and wild-type isolates revealed that most mutations were concentrated in genes associated with membrane metabolism, indicating the most likely target of Pln149-PEP20. Synchrotron radiation circular dichroism showed how this molecule disturbs the membranes, suggesting a carpet mode of interaction. Membrane depolarization and transmission electron microscopy assays supported these two hypotheses, although a secondary intracellular mechanism of action is possible. The molecule studied in this research has the potential to be used as a novel antimicrobial therapy, although further modifications and optimization remain possible.
@article={003121882,author = {RIGHETTO, Gabriela Marinho; LOPES, José Luiz de Souza; BISPO, Paulo José Martins; ANDRÉ, Camille; SOUZA, Julia Medeiros; ANDRICOPULO, Adriano Defini; BELTRAMINI, Leila Maria; CAMARGO, Ilana Lopes Baratella da Cunha.},title={Antimicrobial activity of an Fmoc-Plantaricin 149 derivative peptide against multidrug-resistant bacteria},journal={Antibiotics},note={v. 12, n. 2, p. 391-1-391-27},year={2023}}