title: Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria.
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.
authors.affiliation: Instituto de Medicina Molecular, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Inês M
authors.initials: IM
authors.lastname: Torcato
authors.forename: Yen-Hua
authors.initials: YH
authors.lastname: Huang
authors.forename: Henri G
authors.initials: HG
authors.lastname: Franquelim
authors.forename: Diana
authors.initials: D
authors.lastname: Gaspar
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
authors.forename: Miguel A R B
authors.initials: MA
authors.lastname: Castanho
authors.forename: Sónia
authors.initials: S
authors.lastname: Troeira Henriques
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D016923:Cell Death; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D018625:Microscopy, Atomic Force / Q000379:methods; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D055672:Static Electricity; D020349:Surface Plasmon Resonance / Q000379:methods; D013682:Teichoic Acids / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D008055:Lipids; D008070:Lipopolysaccharides; D010455:Peptides; C579490:R-BP100 peptide; C579491:RW-BP100 peptide; D013682:Teichoic Acids; C009900:lipoteichoic acid; D014364:Tryptophan