Functional synergism of the magainins PGLa and magainin-2 in Escherichia coli, tumor cells and liposomes.
Xenopus laevis skin secretion contains a mixture of magainins, which are small positively charged oligopeptides with antimicrobial activity. In this study, we show that two of these peptides, i.e. magainin-2 and PGLa, are much more active in biological functions when added together than when added alone. This synergy applies for the antimicrobial activity of these peptides, and for the toxic effects on tumor cells. We show that this peptide combination is also synergistic when permeabilizing protein-free liposomes for glucose, when dissipating the membrane potential in cytochrome oxidase liposomes and Escherichia coli, and, reversibly, when stimulating respiration in the liposomes. The occurrence of synergy in these diverse systems (complex and simple) suggests that the biological synergy results from synergy in the primary activity of the magainin peptides, namely the permeabilization of free-energy transducing membranes, possibly by forming a multimeric transmembrane pore of mixed peptide composition. The antimicrobial activity of X. laevis skin secretions may be greatly enhanced by the application of this binary weapon.
Westerhoff
H V
HV
Division of Molecular Biology, Netherlands Cancer Institute/AvL.
Zasloff
M
M
Rosner
J L
JL
Hendler
R W
RW
De Waal
A
A
Vaz Gomes
A
A
Jongsma
P M
PM
Riethorst
A
A
Juretić
D
D
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004357:Drug Synergism; D003576:Electron Transport Complex IV / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D054806:Magainins; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011402:Pronase / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D008081:Liposomes; D054806:Magainins; D010455:Peptides; D029867:Xenopus Proteins; C045866:peptide-Gly-Leu-amide; C053301:magainin 2 peptide, Xenopus; D003576:Electron Transport Complex IV; D011402:Pronase; D005947:Glucose