title: Antimicrobial peptides at work: interaction of myxinidin and its mutant WMR with lipid bilayers mimicking the P. aeruginosa and E. coli membranes.
abstract: Antimicrobial peptides are promising candidates as future therapeutics in order to face the problem of antibiotic resistance caused by pathogenic bacteria. Myxinidin is a peptide derived from the hagfish mucus displaying activity against a broad range of bacteria. We have focused our studies on the physico-chemical characterization of the interaction of myxinidin and its mutant WMR, which contains a tryptophan residue at the N-terminus and four additional positive charges, with two model biological membranes (DOPE/DOPG 80/20 and DOPE/DOPG/CL 65/23/12), mimicking respectively Escherichia coli and Pseudomonas aeruginosa membrane bilayers. All our results have coherently shown that, although both myxinidin and WMR interact with the two membranes, their effect on membrane microstructure and stability are different. We further have shown that the presence of cardiolipin plays a key role in the WMR-membrane interaction. Particularly, WMR drastically perturbs the DOPE/DOPG/CL membrane stability inducing a segregation of anionic lipids. On the contrary, myxinidin is not able to significantly perturb the DOPE/DOPG/CL bilayer whereas interacts better with the DOPE/DOPG bilayer causing a significant perturbing effect of the lipid acyl chains. These findings are fully consistent with the reported greater antimicrobial activity of WMR against P. aeruginosa compared with myxinidin.
authors.affiliation: Department of Experimental Medicine, Università della Campania "Luigi Vanvitelli", via De Crecchio, 80134 Naples, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lombardi
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", via Cintia, 80126 Naples, Italy.
authors.forename: Marco Ignazio
authors.initials: MI
authors.lastname: Stellato
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", via Cintia, 80126 Naples, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Oliva
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Falanga
authors.affiliation: Department of Experimental Medicine, Università della Campania "Luigi Vanvitelli", via De Crecchio, 80134 Naples, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Galdiero
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", via Cintia, 80126 Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Petraccone
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", via Cintia, 80126 Naples, Italy.
authors.forename: Geradino
authors.initials: G
authors.lastname: D'Errico
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", via Cintia, 80126 Naples, Italy.
authors.forename: Augusta
authors.initials: A
authors.lastname: De Santis
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Galdiero
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", via Cintia, 80126 Naples, Italy.
authors.forename: Pompea
authors.initials: P
authors.lastname: Del Vecchio
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects / Q000472:pathogenicity; D029941:Fish Proteins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008051:Lipid Bilayers / Q000037:antagonists & inhibitors / Q000737:chemistry; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D023181:Antimicrobial Cationic Peptides; D029941:Fish Proteins; D008051:Lipid Bilayers; D050505:Mutant Proteins; D009842:Oligopeptides; C000601319:myxinidin peptide, Myxine glutinosa