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Synergistic effects of the membrane actions of cecropin-melittin antimicrobial hybrid peptide BP100

BP100 (KKLFKKILKYL-NH2) is a short cecropin A-melittin hybrid peptide, obtained through a combinatorial chemistry approach, which is highly effective in inhibiting both the in vitro and in vivo growth of economically important plant pathogenic Gram-negatives. The intrinsic Tyr fluorescence of BP100 was taken advantage of to study the peptide’s binding affinity and damaging effect on phospholipid bilayers modeling the bacterial and mammalian cytoplasmic membranes. In vitro cytotoxic effects of this peptide were also studied on mammalian fibroblast cells. Results show a stronger selectivity of BP100 toward anionic bacterial membrane models as indicated by the high obtained partition constants, one order of magnitude greater than for the neutral mammalian membrane models. For the anionic systems, membrane saturation was observed at high peptide/lipid ratios and found to be related with BP100-induced vesicle permeabilization, membrane electroneutrality, and vesicle aggregation. Occurrence of BP100 translocation was unequivocally detected at both high and low peptide/lipid ratios using a novel and extremely simple method. Moreover, cytotoxicity against mammalian models was reached at a concentration considerably higher than the minimum inhibitory concentration. Our findings unravel the relationships among the closely coupled processes of charge neutralization, permeabilization, and translocation in the mechanism of action of antimicrobial peptides

This work was supported by grants from the Ministry of Education and Science of Spain (No. AGL2006-13564/AGR), and from the Catalan Government (No. 2005SGR00275)

© Biophysical Journal, 2009, vol. 96, núm. 5, p. 1815-1827

Biophysical Society

Author: Ferre Malagon, Rafael
Melo, Manuel N.
Correia, Ana Dulce
Feliu Soley, Lídia
Bardají Rodríguez, Eduard
Planas i Grabuleda, Marta
Castanho, Miguel Augusto Rico Botas
Date: 2009
Abstract: BP100 (KKLFKKILKYL-NH2) is a short cecropin A-melittin hybrid peptide, obtained through a combinatorial chemistry approach, which is highly effective in inhibiting both the in vitro and in vivo growth of economically important plant pathogenic Gram-negatives. The intrinsic Tyr fluorescence of BP100 was taken advantage of to study the peptide’s binding affinity and damaging effect on phospholipid bilayers modeling the bacterial and mammalian cytoplasmic membranes. In vitro cytotoxic effects of this peptide were also studied on mammalian fibroblast cells. Results show a stronger selectivity of BP100 toward anionic bacterial membrane models as indicated by the high obtained partition constants, one order of magnitude greater than for the neutral mammalian membrane models. For the anionic systems, membrane saturation was observed at high peptide/lipid ratios and found to be related with BP100-induced vesicle permeabilization, membrane electroneutrality, and vesicle aggregation. Occurrence of BP100 translocation was unequivocally detected at both high and low peptide/lipid ratios using a novel and extremely simple method. Moreover, cytotoxicity against mammalian models was reached at a concentration considerably higher than the minimum inhibitory concentration. Our findings unravel the relationships among the closely coupled processes of charge neutralization, permeabilization, and translocation in the mechanism of action of antimicrobial peptides
This work was supported by grants from the Ministry of Education and Science of Spain (No. AGL2006-13564/AGR), and from the Catalan Government (No. 2005SGR00275)
Format: application/pdf
ISSN: 0006-3495 (versió paper)
1542-0086 (versió electrònica)
Document access: http://hdl.handle.net/10256/12314
Language: eng
Publisher: Biophysical Society
Collection: MEC/PN 2006-2009/ AGL2006-13564-C02-02/AGR
AGAUR/2005-2008/2005 SGR-275
Reproducció digital del document publicat a: http://dx.doi.org/10.1016/j.bpj.2008.11.053
Articles publicats (D-Q)
Is part of: © Biophysical Journal, 2009, vol. 96, núm. 5, p. 1815-1827
Rights: Tots els drets reservats
Subject: Antibiòtics pèptids
Peptide antibiotics
Pèptids -- Síntesi
Peptides -- Synthesis
Antibiòtics pèptids
Peptide antibiotics
Title: Synergistic effects of the membrane actions of cecropin-melittin antimicrobial hybrid peptide BP100
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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