Publicação
Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria
| dc.contributor.author | Torcato, Inês M. | |
| dc.contributor.author | Huang, Yen-Hua | |
| dc.contributor.author | Franquelim, Henri G. | |
| dc.contributor.author | Gaspar, Diana | |
| dc.contributor.author | Craik, David J. | |
| dc.contributor.author | Castanho, Miguel A. R. B. | |
| dc.contributor.author | Henriques, Sónia Troeira | |
| dc.date.accessioned | 2014-03-06T11:37:53Z | |
| dc.date.available | 2014-03-06T11:37:53Z | |
| dc.date.issued | 2013 | |
| dc.description | © 2012 Elsevier B.V. All rights reserved. | eng |
| dc.description.abstract | BP100 is a short cationic antimicrobial peptide with a mechanism of action dependent on peptide–lipid interactions and microbial surface charge neutralization. Although active against Gram-negative bacteria, BP100 is inactive against Gram-positive bacteria. In this study we report two newly designed BP100 analogues, RW-BP100 and R-BP100 that have the Tyr residue replaced with a Trp and/or the Lys residues replaced with an Arg. The new analogues in addition to being active against Gram-negative bacteria, possess activity against all tested Gram-positive bacteria. Mechanistic studies using atomic force microscopy, surface plasmon resonance and fluorescence methodologies reveal that the antibacterial efficiency follows the affinity for bacterial membrane. The studies suggest that the activity of BP100 and its analogues against Gram-negative bacteria is mainly driven by electrostatic interactions with the lipopolysaccharide layer and is followed by binding to and disruption of the inner membrane, whereas activity against Gram-positive bacteria, in addition to electrostatic attraction to the exposed lipoteichoic acids, requires an ability to more deeply insert in the membrane environment, which is favoured with Arg residues and is facilitated in the presence of a Trp residue. Knowledge on the mechanism of action of these antimicrobial peptides provides information that assists in the design of antimicrobials with higher efficacy and broader spectra of action, but also on the design of peptides with higher specificity if required. | eng |
| dc.description.sponsorship | IMT work was supported by a grant (PTDC/SAU-BEB/099142/2008), HGF and DG held a scholarship from the Fundação para a Ciência e Tecnologia, Portugal, SFRH/BD/39039/2007 and SFRH/BPD/73500/2010, respectively. STH is the recipient of a Discovery Early Career Researcher Award (DE120103152), awarded by Australian Research Council. DJC is a National Health and Medical Research Council Fellow. We thank Marta Ribeiro (IMM, Lisbon University) for the valuable scientific discussions. We thank Dr Mark Blaskovich (IMB, UQ) for kindly providing the bacterial strains employed in this study and Angela Kavanagh (IMB, UQ) for the help in establishing the antimicrobial assays. | eng |
| dc.identifier.citation | Biochimica et Biophysica Acta 1828 (2013) 944–955 | eng |
| dc.identifier.issn | 0006-3002 | |
| dc.identifier.uri | http://hdl.handle.net/10451/10694 | |
| dc.identifier.uri | http://dx.doi.org/10.1016/j.bbamem.2012.12.002 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Elsevier | eng |
| dc.relation.publisherversion | The definitive version is available at http://www.elsevier.com | eng |
| dc.subject | Antimicrobial peptide | eng |
| dc.subject | Model membrane | eng |
| dc.subject | Peptide–membrane interaction | eng |
| dc.subject | Atomic force microscopy | eng |
| dc.subject | Trp/Tyr fluorescence | por |
| dc.title | Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria | eng |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 955 | por |
| oaire.citation.startPage | 944 | por |
| oaire.citation.title | Biochimica et Biophysica Acta | eng |
| oaire.citation.volume | 1828 | por |
| rcaap.rights | closedAccess | por |
| rcaap.type | article | por |