title: Killing of Fusobacterium nucleatum, Porphyromonas gingivalis and Prevotella intermedia by protegrins.
abstract: Protegrins are broad spectrum antibiotic peptides isolated from porcine leukocytes. In this study, we (i) examine the sensitivity of Gram-negative, anaerobic periodontal pathogens to synthetic protegrins; (ii) determine the relative potencies of protegrin congeners against these bacteria; and (iii) compare the potency of protegrins with other antibiotic peptides, including magainin MSI-78, tachyplesin I, cecropin P1, human defensins HNP-1-3, and clavanin A. Synthetic L- and D-enantiomers of protegrin 1 (PG-1 and D-PG-1, respectively), and L-enantiomers of protegrins 2, 3 and 5 (PG-2, PG-3 and PG-5) were tested against Fusobacterium nucleatum, and black-pigmented organisms including Porphyromonas gingivalis and Prevotella intermedia. Strains of both F. nucleatum and the black-pigmented organisms were sensitive to PG-1, and exhibited mean ED99 of 2.2-2.3 micrograms/ml and 3.4-9.9 micrograms/ml, respectively. The D-form was statistically more potent than the L-form against these oral anaerobes, and although this difference in potency is unlikely to be of decisive therapeutic significance, the D-form may be of value given ability to resist microbial and host-derived proteases. PG-1 was more potent than magainin, tachyplesin, cecropin, defensins and clavanin under test conditions. Hypertonic salt concentrations and heat-inactivated serum were found to be inhibitory to the bactericidal activity of PG-1. PG-1 was found to induce morphologic alterations in the ultrastructural appearance of F. nucleatum consistent with damage to the bacterial membranes. We conclude that protegrins may be useful antimicrobial agents in therapy against Gram-negative anaerobic bacteria believed to be involved in chronic, adult forms of periodontal infections.
authors.affiliation: Section of Oral Biology, UCLA School of Dentistry 90095-1668, USA. kmiyasak@ucla.edu
authors.forename: K T
authors.initials: KT
authors.lastname: Miyasaki
authors.forename: R
authors.initials: R
authors.lastname: Iofel
authors.forename: A
authors.initials: A
authors.lastname: Oren
authors.forename: T
authors.initials: T
authors.lastname: Huynh
authors.forename: R I
authors.initials: RI
authors.lastname: Lehrer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D015169:Colony Count, Microbial; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000494:pharmacology; D023082:Defensins; D016967:Fusobacterium nucleatum / Q000187:drug effects; D006089:Gram-Negative Anaerobic Bacteria / Q000187:drug effects*; D054806:Magainins; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000187:drug effects; D018713:Prevotella intermedia / Q000187:drug effects; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology; D013552:Swine; D018675:Toxicity Tests; D029867:Xenopus Proteins; D023084:alpha-Defensins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004268:DNA-Binding Proteins; D023082:Defensins; D054806:Magainins; D010455:Peptides; D010456:Peptides, Cyclic; D011506:Proteins; D029867:Xenopus Proteins; D023084:alpha-Defensins; C106713:clavanin A; C406413:human neutrophil peptide 1; C094880:protegrin-1; C084516:protegrin-2; C094881:protegrin-3; C094882:protegrin-5; C053301:magainin 2 peptide, Xenopus; C057636:tachyplesin peptide, Tachypleus tridentatus; C070016:cecropin P1-LI; C093828:pexiganan