title: Antibacterial Peptide Nucleic Acid-Antimicrobial Peptide (PNA-AMP) Conjugates: Antisense Targeting of Fatty Acid Biosynthesis.
abstract: Antisense peptide nucleic acid (PNA) oligomers constitute a novel class of potential antibiotics that inhibit bacterial growth via specific knockdown of essential gene expression. However, discovery of efficient, nontoxic delivery vehicles for such PNA oligomers has remained a challenge. In the present study we show that antimicrobial peptides (AMPs) with an intracellular mode of action can be efficient vehicles for bacterial delivery of an antibacterial PNA targeting the essential acpP gene. The results demonstrate that buforin 2-A (BF2-A), drosocin, oncocin 10, Pep-1-K, KLW-9,13-a, (P59→W59)-Tat48-60, BF-2A-RXR, and drosocin-RXR are capable of transporting PNA effectively into E. coli (MICs of 1-4 μM). Importantly, presence of the inner-membrane peptide transporter SbmA was not required for antibacterial activity of PNA-AMP conjugates containing Pep-1-K, KLW-9,13-a, or drosocin-RXR (MICs of 2-4 μM).
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Anna Mette
authors.initials: AM
authors.lastname: Hansen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Bonke
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Camilla Josephine
authors.initials: CJ
authors.lastname: Larsen
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Panum Institute, University of Copenhagen , Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Yavari
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Panum Institute, University of Copenhagen , Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nielsen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Franzyk
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D005227:Fatty Acids / Q000096:biosynthesis*; D008826:Microbial Sensitivity Tests; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids