Membrane Interactions of Novicidin, a Novel Antimicrobial Peptide: Phosphatidylglycerol Promotes Bilayer Insertion

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  • Jerzy Dorosz, Denmark
  • Yana Gofman
  • ,
  • Sofiya Kolusheva, Ben-Gurion University, Israel
  • Daniel Otzen
  • Nir Ben-Tal, Tel Aviv University, Israel
  • Niels Christian Nielsen
  • Raz Jelinek, Ben-Gurion University, Israel
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.
Original languageEnglish
JournalThe Journal of Physical Chemistry B
Volume114
Issue34
Pages (from-to)11053-60
Number of pages8
DOIs
Publication statusPublished - 2010

    Research areas

  • Amino Acid Sequence, Anti-Infective Agents, Antimicrobial Cationic Peptides, Circular Dichroism, Erythrocytes, Hemolysis, Humans, Lipid Bilayers, Microbial Sensitivity Tests, Monte Carlo Method, Phosphatidylglycerols

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