Luzia Holfeld1,2, Nicole Herth1,2, David Singer1,2, Ralf Hoffmann1,2, Daniel Knappe1,2. 1. Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany. 2. Center for Biotechnology and Biomedicine, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany.
Abstract
AIM: The potential of proline-rich antimicrobial peptides (PrAMPs) to treat multidrug-resistant Gram-negative pathogens has been intensively investigated. They are efficacious at low doses in infection models and well tolerated in healthy mice at high doses. METHODS & RESULTS: PrAMPs Onc72 and Api88 were nonimmunogenic in mice unless conjugated to a carrier protein. Monoclonal IgG1/IgG2b antibodies produced by hybridoma cells were mapped to different Onc72 regions and combined in a sandwich-ELISA in a pharmacokinetic study. Onc72 was detected at concentrations up to 32 µg/ml in murine blood after administering 20 mg/kg and reached several organs within 10 min. CONCLUSION: Both PrAMPs were not immunogenic and Onc72 concentrations in blood were well above the minimal inhibitory concentrations for Enterobacteriaceae further confirming their potential as novel antibiotics.
AIM: The potential of proline-rich antimicrobial peptides (PrAMPs) to treat multidrug-resistant Gram-negative pathogens has been intensively investigated. They are efficacious at low doses in infection models and well tolerated in healthy mice at high doses. METHODS & RESULTS: PrAMPs Onc72 and Api88 were nonimmunogenic in mice unless conjugated to a carrier protein. Monoclonal IgG1/IgG2b antibodies produced by hybridoma cells were mapped to different Onc72 regions and combined in a sandwich-ELISA in a pharmacokinetic study. Onc72 was detected at concentrations up to 32 µg/ml in murine blood after administering 20 mg/kg and reached several organs within 10 min. CONCLUSION: Both PrAMPs were not immunogenic and Onc72 concentrations in blood were well above the minimal inhibitory concentrations for Enterobacteriaceae further confirming their potential as novel antibiotics.
Authors: Pavel V Panteleev; Victoria N Safronova; Roman N Kruglikov; Ilia A Bolosov; Ivan V Bogdanov; Tatiana V Ovchinnikova Journal: Membranes (Basel) Date: 2022-05-12