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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

Antibiotics (Basel), 2023-02, Vol.12 (2), p.391 [Periódico revisado por pares]

Switzerland: MDPI AG

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Antimicrobial Activity of an Fmoc-Plantaricin 149 Derivative Peptide against Multidrug-Resistant Bacteria
Autor: 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
Assuntos: Antibiotics ; Antimicrobial activity ; Antimicrobial agents ; Antimicrobial peptides ; Antimicrobial resistance ; Bacteria ; Bactericidal activity ; Biomass ; Cancer ; carpet-like mechanism ; Circular dichroism ; Cytotoxicity ; Depolarization ; Dichroism ; Drug resistance ; Drug resistance in microorganisms ; Evolution ; Gene sequencing ; Genomes ; Gram-negative bacteria ; Gram-positive bacteria ; Health aspects ; Health risks ; Membrane potential ; Membranes ; Metabolism ; Multidrug resistance ; Mutation ; Optimization ; Peptides ; Plantaricin 149 ; Public health ; Radiation ; Staphylococcus infections ; Synchrotron radiation ; Synchrotrons ; synergism ; Transmission electron microscopy ; Whole genome sequencing
É parte de: Antibiotics (Basel), 2023-02, Vol.12 (2), p.391
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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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

Switzerland: MDPI AG

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