Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria

Torcato, Inês M., Huang, Yen-Hua, Franquelim, Henri G., Gaspar, Diana, Craik, David J., Castanho, Miguel A. R. B. and Henriques, Sonia Troeira (2013) Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria. Biochimica et Biophysica Acta, 1828 3: 944-955. doi:10.1016/j.bbamem.2012.12.002


Author Torcato, Inês M.
Huang, Yen-Hua
Franquelim, Henri G.
Gaspar, Diana
Craik, David J.
Castanho, Miguel A. R. B.
Henriques, Sonia Troeira
Title Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria
Journal name Biochimica et Biophysica Acta   Check publisher's open access policy
ISSN 0006-3002
Publication date 2013-03-01
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.bbamem.2012.12.002
Volume 1828
Issue 3
Start page 944
End page 955
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2013
Language eng
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.
Keyword Antimicrobial peptide
Model membrane
Peptide–membrane interaction
Atomic force microscopy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 13 December 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 21 Jan 2013, 19:46:57 EST by Susan Allen on behalf of Institute for Molecular Bioscience