Different mechanisms of action of antimicrobial peptides: insights from fluorescence spectroscopy experiments and molecular dynamics simulations.
Most antimicrobial peptides exert their activity by interacting with bacterial membranes, thus perturbing their permeability. They are investigated as a possible solution to the insurgence of bacteria resistant to the presently available antibiotic drugs. However, several different models have been proposed for their mechanism of membrane perturbation, and the molecular details of this process are still debated. Here, we compare fluorescence spectroscopy experiments and molecular dynamics (MD) simulations regarding the association with lipid bilayers and lipid perturbation for two different amphiphilic helical antimicrobial peptides, PMAP-23 and trichogin GA IV. PMAP-23, a cationic peptide member of the cathelicidin family, is considered to induce membrane permeability according to the Shai-Matsuzaki-Huang "carpet" model, while trichogin GA IV is a neutral peptide, member of the peptaibol family. Although several lines of evidence suggest a "barrel-stave" mechanism of pore formation for the latter peptide, its length is only half the normal thickness of a lipid bilayer. Both fluorescence spectroscopy experiments and MD simulations indicated that PMAP-23 associates with membranes close to their surface and parallel to it, and in this arrangement it causes a severe perturbation to the bilayer, both regarding its surface tension and lipid order. By contrast, trichogin GA IV can undergo a transition from a surface-bound state to a transmembrane orientation. In the first arrangement, it does not cause any strong membrane perturbation, while in the second orientation it might be able to span the bilayer from one side to the other, despite its relatively short length, by causing a significant thinning of the membrane.
Bocchinfuso
Gianfranco
G
Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, 00133 Rome, Italy.
Palleschi
Antonio
A
Orioni
Barbara
B
Grande
Giacinto
G
Formaggio
Fernando
F
Toniolo
Claudio
C
Park
Yoonkyung
Y
Hahm
Kyung-Soo
KS
Stella
Lorenzo
L
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry; D055666:Lipopeptides / Q000737:chemistry; D008962:Models, Theoretical; D013050:Spectrometry, Fluorescence / Q000379:methods*
D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D055666:Lipopeptides; C086301:porcine myeloid antibacterial peptide 23; C116419:trichogin GA IV