title: Oncocin Onc72 is efficacious against antibiotic-susceptible Klebsiella pneumoniae ATCC 43816 in a murine thigh infection model.
abstract: Oncocins and apidaecins are short proline-rich antimicrobial peptides (PrAMPs) representing novel antibiotic drug lead compounds that kill bacteria after internalization and inhibition of intracellular targets (e.g. 70S ribosome and DnaK). Oncocin Onc72 is highly active against Gram-negative bacteria in vitro and in vivo protecting mice in systemic infection models with Escherichia coli and KPC-producing Klebsiella pneumoniae. Here we studied its efficacy in a murine thigh infection model using meropenem as antibiotic comparator that had a 44-fold higher molar in vitro activity than Onc72. Male CD1 mice were rendered neutropenic using cyclophosphamide for four days before intramuscular infection with K. pneumoniae ATCC 43816. After 75 min oncocin Onc72 or the antibiotic comparator meropenem were administered subcutaneously with 100 mg (43 µmol) and 25 mg (65 µmol) per kg of body weight, respectively, six times every 75 min. Onc72 and meropenem administered subcutaneously reduced the thigh tissue burden of K. pneumoniae ATCC 43816 in neutropenic mice significantly by 4.14 and 4.65 a log10 cfu/g, respectively. The bacterial counts were ∼0.5 and ∼1 log10 below the pre-treatment burden, respectively, indicating bactericidal effects for both compounds. Thus, Onc72 was as efficacious as meropenem in vivo despite its much lower in vitro activity determined according to CLSI standard antimicrobial activity tests.
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig, Germany.|Center for Biotechnology and Biomedicine, Universität Leipzig, Leipzig, Germany.|AMP-Therapeutics GmbH, Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Knappe
authors.affiliation: AMP-Therapeutics GmbH, Leipzig, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Adermann
authors.affiliation: Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig, Germany.|Center for Biotechnology and Biomedicine, Universität Leipzig, Leipzig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D051379:Mice; D018482:Muscle, Skeletal / Q000382:microbiology*
chemical_list: D023181:Antimicrobial Cationic Peptides; C551620:oncocin
keywords: Klebsiella pneumonia; antimicrobial peptide; meropenem; oncocin; proline-rich; thigh infection