title: A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.
abstract: Eradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and/or biofilm forms of Pseudomonas aeruginosa strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain ester.boix@uab.cat David.Pulido@e-campus.uab.cat.
authors.forename: David
authors.initials: D
authors.lastname: Pulido
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Prats-Ejarque
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Villalba
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Marcel
authors.initials: M
authors.lastname: Albacar
authors.affiliation: Microbiology Service, Hospital del Valle Hebron, Barcelona, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: González-López
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Torrent
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Moussaoui
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain ester.boix@uab.cat David.Pulido@e-campus.uab.cat.
authors.forename: Ester
authors.identifier: 0000-0003-1790-2142
authors.initials: E
authors.lastname: Boix
mesh_terms: D000371:Agglutination / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D047150:Eosinophil Cationic Protein / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010933:Plankton / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human