title: Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: potent activity against oral pathogens.
abstract: Cationic amphipathic α-helical peptides are intensively studied classes of host defence peptides (HDPs). Three peptides, peptide glycine-leucine-amide (PGLa-AM1), caerulein-precursor fragment (CPF-AM1) and magainin-AM1, originally isolated from norepinephrine-stimulated skin secretions of the African volcano frog Xenopus amieti (Pipidae), were studied for their antimicrobial and immunomodulatory activities against oral and respiratory pathogens. Minimal effective concentrations (MECs), determined by radial diffusion assay, were generally lower than minimal inhibitory concentrations (MICs) determined by microbroth dilution. PGLa-AM1 and CPF-AM1 were particularly active against Streptococcus mutans and all three peptides were effective against Fusobacterium nucleatum, whereas Enterococcus faecalis and Candida albicans proved to be relatively resistant micro-organisms. A type strain of Pseudomonas aeruginosa was shown to be more susceptible than the clinical isolate studied. PGLa-AM1 displayed the greatest propensity to bind lipopolysaccharide (LPS) from Escherichia coli, P. aeruginosa and Porphyromonas gingivalis. All three peptides showed less binding to P. gingivalis LPS than to LPS from the other species studied. Oral fibroblast viability was unaffected by 50 μM peptide treatments. Production of the pro-inflammatory cytokine IL-8 by oral fibroblasts was significantly increased following treatment with 1 or 10 μM magainin-AM1 but not following treatment with PGLa-AM1 or CPF-AM1. In conclusion, as well as possessing potent antimicrobial actions, the X. amieti peptides bound to LPS from three human pathogens and had no effect on oral fibroblast viability. CPF-AM1 and PGLa-AM1 show promise as templates for the design of novel analogues for the treatment of oral and dental diseases associated with bacteria or fungi.
authors.affiliation: Centre for Infection & Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, Northern Ireland, UK.
authors.forename: Denise T F
authors.initials: DT
authors.lastname: McLean
authors.affiliation: Centre for Infection & Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, Northern Ireland, UK.
authors.forename: Maelíosa T C
authors.initials: MT
authors.lastname: McCrudden
authors.affiliation: Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, Northern Ireland, UK.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Linden
authors.affiliation: Centre for Dentistry, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, Northern Ireland, UK.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Irwin
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, 17666 Al-Ain, United Arab Emirates.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
authors.affiliation: Centre for Infection & Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, Northern Ireland, UK. Electronic address: f.lundy@qub.ac.uk.
authors.forename: Fionnuala T
authors.initials: FT
authors.lastname: Lundy
mesh_terms: D029845:Amphibian Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D016967:Fusobacterium nucleatum / Q000187:drug effects; D016209:Interleukin-8 / Q000096:biosynthesis; D054806:Magainins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009055:Mouth / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D013295:Streptococcus mutans / Q000187:drug effects; D013329:Structure-Activity Relationship; D014981:Xenopus; D029867:Xenopus Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; C582629:CPF-AM1 peptide, Xenopus; D016209:Interleukin-8; D054806:Magainins; C000603829:PGLa-AM1 peptide, Xenopus amieti; D029867:Xenopus Proteins; C582630:magainin-AM1, Xenopus
keywords: Antimicrobial peptide; Cytokine; Host defence peptide; Lipopolysaccharide