title: Short Proline-Rich Antimicrobial Peptides Inhibit Either the Bacterial 70S Ribosome or the Assembly of its Large 50S Subunit.
abstract: Short proline-rich antimicrobial peptides (PrAMPs) are a promising class of antibiotics that use novel mechanisms, thus offering the potential to overcome the health threat of multiresistant pathogens. The peptides bind to the bacterial 70S ribosome and can inhibit protein translation. We report that PrAMPs can be divided into two classes, with each class binding to a different site, and thus use different lethal mechanisms. Oncocin-type peptides inhibit protein translation in Escherichia coli by binding to the exit tunnel of the 70S ribosome with half maximal inhibitory concentrations (IC50 values) of around 2 to 6 μmol  L(-1), whereas apidaecin-type peptides block the assembly of the large (50S) subunit of the ribosome, resulting in similar IC50 values. The revealed mechanisms should allow the design of new antibiotics to overcome current bacterial resistance mechanisms.
authors.affiliation: Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany.
authors.forename: Andor
authors.initials: A
authors.lastname: Krizsan
authors.affiliation: Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Prahl
authors.affiliation: Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Goldbach
authors.affiliation: Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Knappe
authors.affiliation: Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany. hoffmann@chemie.uni-leipzig.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054681:Ribosome Subunits, Large, Bacterial / Q000737:chemistry / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; C061361:apidaecin; D011392:Proline
keywords: Gram-negative bacteria; antibiotics; apidaecin; oncocin; peptides; protein translation