Can we predict biological activity of antimicrobial peptides from their interactions with model phospholipid membranes?
Cationic antibacterial peptides are produced in all living organisms and possess either selective activity toward a certain type of cell or microorganism, or a broad spectrum of activity toward several types of cells including prokaryotic and mammalian cells. In order to exert their activity, peptides first interact with and traverse an outer barrier, e.g., mainly LPS and peptidoglycan in bacteria or a glycocalix layer and matrix proteins in mammalian cells. Only then, can the peptides bind and insert into the cytoplasmic membrane. The mode of action of many antibacterial peptides is believed to be the disruption of the lipidic plasma membrane. Therefore, model phospholipid membranes have been used to study the mode of action of antimicrobial peptides. These studies have demonstrated that peptides that act preferentially on bacteria are also able to interact with and permeate efficiently anionic phospholipids, whereas peptides that lyse mammalian cells bind and permeate efficiently both acidic and zwitterionic phospholipids membranes, mimicking the plasma membranes of these cells. It is now becoming increasingly clear that selective activity of these peptides against different cells depends also on other parameters that characterize both the peptide and the target cell. With respect to the peptide's properties, these include the volume of the molecule, its structure, and its oligomeric state in solution and in membranes. Regarding the target membrane, these include the structure, length, and complexity of the hydrophilic polysaccharide found in its outer layer. These parameters affect the ability of the peptides to diffuse through the cell's outer barrier and to reach its cytoplasmic plasma membrane.
Papo
Niv
N
Department of Biological Chemistry, The Weizmann Institute of Science, Herzel Street, Rehovot 76100, Israel.
Shai
Yechiel
Y
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008567:Membranes, Artificial; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D008567:Membranes, Artificial; D010743:Phospholipids