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Author(s): Claudia Monteiro
Mariana Fernandes
Marina Pinheiro
Silvia Maia
Catarina L Seabra
Frederico Ferreira da Silva
Fabiola Costa
Salette Reis
Paula Gomes
Cristina C L Martins
Title: Antimicrobial properties of membrane-active dodecapeptides derived from MSI-78
Issue Date: 2015
Abstract: Antimicrobial peptides (AMPs) are a class of broad-spectrum antibiotics known by their ability to disrupt bacterial membranes and their low tendency to induce bacterial resistance, arising as excellent candidates to fight bacterial infections. In this study we aimed at designing short 12-mer AMPs, derived from a highly effective and broad spectrum synthetic AMP, MSI-78 (22 residues), by truncating this peptide at the N- and/or C-termini while spanning its entire sequence with 1 amino add (aa) shifts. These designed peptides were evaluated regarding antimicrobial activity against selected gram-positive Staphylococcus strains and the gram-negative Pseudomonas aeruginosa (P. aeruginosa). The short 12-mer peptide CEM1 (GIGMFLKKAKICF) was identified as an excellent candidate to fight P. aeruginosa infections as it displays antimicrobial activity against this strain and selectivity, with negligible toxicity to mammalian cells even at high concentrations. However, in general most of the short 12-mer peptides tested showed a reduction in antimicrobial activity, an effect that was more pronounced for gram-positive Staphylococcus strains. Interestingly, CEM1 and a highly similar peptide differing by only one aa-shift (CEM2: IGKFLKKAKICFG), showed a remarkably contrasting AMP activity. These two peptides were chosen for a more detailed study regarding their mechanism of action, using several biophysical assays and simple membrane models that mimic the mammalian and bacterial lipid composition. We confirmed the correlation between peptide helicity and antimicrobial activity and propose a mechanism of action based on the disruption of the bacterial membrane permeability barrier.
Subject: Ciências biológicas
Biological sciences
Scientific areas: Ciências exactas e naturais::Ciências biológicas
Natural sciences::Biological sciences
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:FCUP - Artigo em Revista Científica Internacional
FFUP - Artigo em Revista Científica Internacional

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