Molecular Basis for Membrane Selectivity of Antimicrobial Peptide Pleurocidin in the Presence of Different Eukaryotic and Prokaryotic Model Membranes

Abstract

Pleurocidin, a 25-residue cationic peptide, has antimicrobial activity against bacteria and fungi but exhibits very low hemolytic activity against human red blood cells (RBC). The peptide inserts into the bacterial membrane and causes the membrane to become permeable by either toroidal or carpet mechanism. Herein, to investigate the molecular basis for membrane selectivity of Pleurocidin, the interaction of the peptide with the different membrane models including the RBC, DOPC, DOPC/DOPG (3:1), POPE/POPG (3:1), and POPE/POPG (1:3) bilayers were studied by performing all-atom molecular dynamics (MD) simulation. The MD results indicated that the peptide interacted weakly with the neutral phospholipid bilayers (DOPC), whereas it made strong interactions with the negatively charged phospholipids. Pleurocidin maintained its α-helical structure during interactions with the anionic model membranes, but the peptide lost its secondary structure adjacent to the neutral model membranes. The results also revealed that the Trp-2, Phe-5, and Phe-6 residues, located in the N-terminal region of the peptide, played major roles in the insertion of the peptide into the model membranes. In addition, the peptide deeply inserted into the DOPC/DOPG membrane. The order analysis showed that Pleurocidin affected the order of anionic phospholipids more than zwitterionic phospholipids. The cholesterol molecules help the RBC membrane conserve integrity in response to Pleurocidin. This research has provided data on the Pleurocidin–membrane interactions and the reasons of resistance of eukaryotic membrane to the Pleurocidin at atomic details that are useful to develop potent AMPs targeting multidrug-resistant bacteria.

[Retracted] Atomic Scale Interactions between RNA and DNA Aptamers with the TNF‐α Protein

“…Moreover, the results of the contact number analyses have shown the significant role of the basic residues of TNF-α that have in the interactions with aptamers. Previous investigations indicate that in the interactions with anionic molecules such as antimicrobial peptides and nucleic acids the basic residues in the proteins play a major role [72,73].…”

Investigating Potential Applications of the Fish Anti-Microbial Peptide Pleurocidin: A Systematic Review

“…This amphipathic property allows for pleurocidin to actively interact with the polar and nonpolar components of cell membranes. Studies that investigate the action of AMPs such as pleurocidin typically use model membranes composed of zwitterionic phosphatidylcholine (PC) or phosphatidylcholine/phosphatidylglycerol (PC/PG) membranes to elucidate the peptide interactions with various types of membrane bilayers [ 36 , 37 ]. Upon contact with anionic membranes, pleurocidin conforms to an α-helix [ 37 ].…”

“…Studies that investigate the action of AMPs such as pleurocidin typically use model membranes composed of zwitterionic phosphatidylcholine (PC) or phosphatidylcholine/phosphatidylglycerol (PC/PG) membranes to elucidate the peptide interactions with various types of membrane bilayers [ 36 , 37 ]. Upon contact with anionic membranes, pleurocidin conforms to an α-helix [ 37 ]. Like other AMPs, the tryptophan residues on the peptide allow pleurocidin to anchor to the membrane surface [ 37 ].…”

“…Upon contact with anionic membranes, pleurocidin conforms to an α-helix [ 37 ]. Like other AMPs, the tryptophan residues on the peptide allow pleurocidin to anchor to the membrane surface [ 37 ]. The formation of this secondary structure occurs in the presence of charged molecules; pleurocidin does not conform to a helix in the presence of zwitterionic phospholipids [ 36 , 37 ].…”

“…Like other AMPs, the tryptophan residues on the peptide allow pleurocidin to anchor to the membrane surface [ 37 ]. The formation of this secondary structure occurs in the presence of charged molecules; pleurocidin does not conform to a helix in the presence of zwitterionic phospholipids [ 36 , 37 ]. The reason behind this is due to electrostatic repulsions between the NH 3 groups of aromatic residues of the peptide and the positive charge of choline on the neutral phospholipids [ 37 ].…”