Membrane curvature stress and antibacterial activity of lactoferricin derivatives.
We have studied correlation of non-lamellar phase formation and antimicrobial activity of two cationic amphipathic peptides, termed VS1-13 and VS1-24 derived from a fragment (LF11) of human lactoferricin on Escherichia coli total lipid extracts. Compared to LF11, VS1-13 exhibits minor, but VS1-24 significantly higher antimicrobial activity. X-ray experiments demonstrated that only VS1-24 decreased the onset of cubic phase formation of dispersions of E. coli lipid extracts, significantly, down to physiological relevant temperatures. Cubic structures were identified to belong to the space groups Pn3m and Im3m. Formation of latter is enhanced in the presence of VS1-24. Additionally, the presence of this peptide caused membrane thinning in the fluid phase, which may promote cubic phase formation. VS1-24 containing a larger hydrophobic volume at the N-terminus than its less active counterpart VS1-13 seems to increase curvature stress in the bilayer and alter the behaviour of the membrane significantly enhancing disruption.
Zweytick
Dagmar
D
Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Schmiedlstrasse 6, A-8042 Graz, Austria.
Tumer
Sabine
S
Blondelle
Sylvie E
SE
Lohner
Karl
K
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D004548:Elasticity; D004926:Escherichia coli / Q000737:chemistry*; D007781:Lactoferrin / Q000737:chemistry*; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry*; D008968:Molecular Conformation; D013314:Stress, Mechanical; D013499:Surface Properties
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008563:Membrane Lipids; C082171:lactoferricin B; D007781:Lactoferrin