Lantibiotics, a group of lanthionine-containing peptides, display their 
antibiotic activity by combining different killing mechanisms within one 
molecule. The prototype lantibiotic nisin was shown to possess both inhibition 
of peptidoglycan synthesis and pore formation in bacterial membranes by 
interacting with lipid II. Gallidermin, which shares the lipid II binding motif 
with nisin but has a shorter molecular length, differed from nisin in pore 
formation in several strains of bacteria. To simulate the mode of action, we 
applied cyclic voltammetry and quartz crystal microbalance to correlate pore 
formation with lipid II binding kinetics of gallidermin in model membranes. The 
inability of gallidermin to form pores in DOPC 
(1,2-dioleoyl-sn-glycero-3-phosphocholine) (C18/1) and DPoPC 
(1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine) (C16/1) membranes was related 
to the membrane thickness. For a better simulation of bacterial membrane 
characteristics, two different phospholipids with branched fatty acids were 
incorporated into the DPoPC matrix. Phospholipids with methyl branches in the 
middle of the fatty acid chains favored a lipid II-independent DPoPC 
permeabilization by gallidermin, while long-branched phospholipids in which the 
branch is placed near the hydrophilic region induced an identical lipid 
II-dependent pore formation of gallidermin and nisin. Obviously, the branched 
lipids altered lipid packing and reduced the membrane thickness. Therefore, the 
duality of gallidermin activity (pore formation and inhibition of the cell wall 
synthesis) seems to be balanced by the bacterial membrane composition.