title: Insect-derived proline-rich antimicrobial peptides kill bacteria by inhibiting bacterial protein translation at the 70S ribosome.
abstract: Proline-rich antimicrobial peptides (PrAMPs) have been investigated and optimized by several research groups and companies as promising lead compounds to treat systemic infections caused by Gram-negative bacteria. PrAMPs, such as apidaecins and oncocins, enter the bacteria and kill them apparently through inhibition of specific targets without a lytic effect on the membranes. Both apidaecins and oncocins were shown to bind with nanomolar dissociation constants to the 70S ribosome. In apidaecins, at least the two C-terminal residues (Arg17 and Leu18) interact strongly with the 70S ribosome, whereas residues Lys3, Tyr6, Leu7, and Arg11 are the major interaction sites in oncocins. Oncocins inhibited protein biosynthesis very efficiently in vitro with half maximal inhibitory concentrations (IC50 values) of 150 to 240 nmol L(-1). The chaperone DnaK is most likely not the main target of PrAMPs but it binds them with lower affinity.
authors.affiliation: Institut für Bioanalytische Chemie, Biotechnologisch-Biomedizinisches Zentrum (BBZ), Universität Leipzig, Deutscher Platz 5, 04103 Leipzig (Germany).
authors.forename: Andor
authors.initials: A
authors.lastname: Krizsan
authors.forename: Daniela
authors.initials: D
authors.lastname: Volke
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weinert
authors.forename: Norbert
authors.initials: N
authors.lastname: Sträter
authors.forename: Daniel
authors.initials: D
authors.lastname: Knappe
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001426:Bacterial Proteins / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D007313:Insecta; D008826:Microbial Sensitivity Tests; D011392:Proline / Q000032:analysis*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012270:Ribosomes / Q000235:genetics*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C551620:oncocin; D011392:Proline
keywords: Gram-negative bacteria; antibiotics; inhibitors; peptides; ribosomes