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 a re small positively charged oligopeptides with antimicrobial activity. In this study, we show that two of these peptides, i.e. magainin-2 an d PGLa, are much more active in biological functions when added togeth er than when added alone. This synergy applies for the antimicrobial a ctivity of these peptides, and for the toxic effects on tumor cells. W e show that this peptide combination is also synergistic when permeabi lizing protein-free liposomes for glucose, when dissipating the membra ne potential in cytochrome oxidase liposomes and Escherichia coli, and , reversibly, when stimulating respiration in the liposomes. The occur rence of synergy in these diverse systems (complex and simple) suggest s that the biological synergy results from synergy in the primary acti vity of the magainin. peptides, namely the permeabilization of free-en ergy transducing membranes, possibly by forming a multimeric transmemb rane pore of mixed peptide composition. The antimicrobial activity of X. laevis skin secretions may be greatly enhanced by the application o f this binary weapon.