title: The functional interaction between abaecin and pore-forming peptides indicates a general mechanism of antibacterial potentiation.
abstract: Long-chain proline-rich antimicrobial peptides such as bumblebee abaecin show minimal activity against Gram-negative bacteria despite binding efficiently to specific intracellular targets. We recently reported that bumblebee abaecin interacts with Escherichia coli DnaK but shows negligible antibacterial activity unless it is combined with sublethal doses of the pore-forming peptide hymenoptaecin. These two bumblebee peptides are co-expressed in vivo in response to a bacterial challenge. Here we investigated whether abaecin interacts similarly with pore-forming peptides from other organisms by replacing hymenoptaecin with sublethal concentrations of cecropin A (0.3 μM) or stomoxyn (0.05 μM). We found that abaecin increased the membrane permeabilization effects of both peptides, confirming that it can reduce the minimal inhibitory concentrations of pore-forming peptides from other species. We also used atomic force microscopy to show that 20 μM abaecin combined with sublethal concentrations of cecropin A or stomoxyn causes profound structural changes to the bacterial cell surface. Our data indicate that the potentiating functional interaction between abaecin and pore-forming peptides is not restricted to specific co-expressed peptides from the same species but is likely to be a general mechanism. Combination therapies based on diverse insect-derived peptides could therefore be used to tackle bacteria that are recalcitrant to current antibiotics.
authors: Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchester Strasse 2, D-35394 Giessen, Germany. Electronic address: Mohammad.Rahnamaeian@agrar.uni-giessen.de.
authors: Mohammad
authors: M
authors: Rahnamaeian
authors: Department of Immunobiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka St. 19, 20-033 Lublin, Poland.
authors: Małgorzata
authors: M
authors: Cytryńska
authors: Department of Immunobiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka St. 19, 20-033 Lublin, Poland.
authors: Agnieszka
authors: A
authors: Zdybicka-Barabas
authors: Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchester Strasse 2, D-35394 Giessen, Germany; Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany.
authors: Andreas
authors: A
authors: Vilcinskas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D001516:Bees / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004338:Drug Combinations; D004357:Drug Synergism; D057075:Enzyme Assays; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D019476:Insect Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D018625:Microscopy, Atomic Force; D009117:Muscidae / Q000737:chemistry; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004338:Drug Combinations; D019476:Insect Proteins; C510762:stomoxyn; C062933:abaecin protein, Apis mellifera; C031161:cecropin A; D001616:beta-Galactosidase
keywords: Atomic force microscopy; Combination therapy; Membrane permeabilization; Proline-rich peptides; Therapeutic leads; β-galactosidase assay