Antimicrobial properties of membrane-active dodecapeptides derived from MSI-78

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Claudia Monteiro (Author) Other; Mariana Fernandes (Author) Other; Marina Pinheiro (Author) Other; Silvia Maia (Author) Other; Catarina L Seabra (Author) Other; Frederico Ferreira da Silva (Author) Other; Fabiola Costa (Author) Other; Salette Reis (Author) FFUP; Paula Gomes (Author) FCUP; Cristina C L Martins (Author) Other

Journal

Title: Biochimica et Biophysica Acta: Biomembranes

Vol. 1848

Pages: 1139-1146

ISSN: 0005-2736

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 27 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-00A-7EQ

DOI: 10.1016/j.bbamem.2015.02.001

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific