melitten and 1-palmitoyl-2-oleoylphosphatidylethanolamine

An understanding of the mechanism of action of antimicrobial peptides is fundamental to the development of new and more active antibiotics. In the present work, we use a wide range of techniques (SANS, SAXD, DSC, ITC, CD, and confocal and electron microscopy) in order to fully characterize the interaction of a cecropin A-melittin hybrid antimicrobial peptide, CA(1-7)M(2-9), of known antimicrobial activity, with a bacterial model membrane of POPE/POPG in an effort to unravel its mechanism of action. We found that CA(1-7)M(2-9) disrupts the vesicles, inducing membrane condensation and forming an onionlike structure of multilamellar stacks, held together by the intercalated peptides. SANS and SAXD revealed changes induced by the peptide in the lipid bilayer thickness and the bilayer stiffening in a tightly packed liquid-crystalline lamellar phase. The analysis of the observed abrupt changes in the repeat distance upon the phase transition to the gel state suggests the formation of an L

Topics: Amino Acid Sequence; Antimicrobial Cationic Peptides; Melitten; Phosphatidylethanolamines; Phosphatidylglycerols

We have studied the influence of four antimicrobial peptides of different secondary and ternary structure--melittin (Mel), protegrin-1 (PG-1), peptidyl-glycylleucine-carboxyamide (PGLa), and gramicidin S (GS)--on the lamellar-to-nonlamellar transition of palmitoyloleoyl phosphatidylethanolamine (POPE) applying differential scanning calorimetry and small-angle X-ray diffraction. None of the peptides studied led to the formation of an inverted hexagonal phase observed for pure POPE at high temperatures. Instead either cubic or lamellar phases were stabilized to different degrees. GS was most effective in inducing a cubic phase, whereas Mel fully stabilized the lamellar phase. The behavior of POPE in the presence of PG-1 and PGLa was intermediate to GS and Mel. In addition to the known role of membrane elasticity we propose two mechanisms, which cause stabilization of the lamellar phase: electrostatic repulsion and lipid/peptide pore formation. Both mechanisms prevent transmembrane contact required to form either an inverted hexagonal phase or fusion pores, as precursors of the cubic phase.

Topics: Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Calorimetry, Differential Scanning; Gramicidin; Lipids; Liposomes; Melitten; Models, Molecular; Phase Transition; Phosphatidylethanolamines; Protein Precursors; Protein Structure, Secondary; Protein Structure, Tertiary; X-Ray Diffraction