Membrane interactions of novicidin, a novel antimicrobial peptide: phosphatidylglycerol promotes bilayer insertion.
Novicidin is an antimicrobial peptide derived from ovispirin, a cationic peptide which originated from the ovine cathelicidin SMAP-29. Novicidin, however, has been designed to minimize the cytotoxic properties of SMAP-29 and ovisipirin toward achieving potential therapeutic applications. We present an analysis of membrane interactions and lipid bilayer penetration of novicidin, using an array of biophysical techniques and biomimetic membrane assemblies, complemented by Monte Carlo (MC) simulations. The data indicate that novicidin interacts minimally with zwitterionic bilayers, accounting for its low hemolytic activity. Negatively charged phosphatidylglycerol, on the other hand, plays a significant role in initiating membrane binding of novicidin, and promotes peptide insertion into the interface between the lipid headgroups and the acyl chains. The significant insertion into bilayers containing negative phospholipids might explain the enhanced antibacterial properties of novicidin. Overall, this study highlights two distinct outcomes for membrane interactions of novicidin, and points to a combination between electrostatic attraction to the lipid/water interface and penetration into the subsurface lipid headgroups region as important determinants for the biological activity of novicidin.
Dorosz
Jerzy
J
Department of Chemistry and Ilse Katz Institute for Nanotechnology, Ben Gurion University, Beer Sheva 84105, Israel.
Gofman
Yana
Y
Kolusheva
Sofiya
S
Otzen
Daniel
D
Ben-Tal
Nir
N
Nielsen
Niels Chr
NC
Jelinek
Raz
R
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D010715:Phosphatidylglycerols / Q000737:chemistry*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; C554278:novicidin; C440189:ovispirin