title: Membrane lipids determine the antibiotic activity of the lantibiotic gallidermin.
abstract: 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.
authors.affiliation: Department of Pharmacy, Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany. kchrist@uni-bonn.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Christ
authors.forename: Saad
authors.initials: S
authors.lastname: Al-Kaddah
authors.forename: Imke
authors.initials: I
authors.lastname: Wiedemann
authors.forename: Bernd
authors.initials: B
authors.lastname: Rattay
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.forename: Gerd
authors.initials: G
authors.lastname: Bendas
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000595:Amino Acid Sequence; D001430:Bacteriocins / Q000737:chemistry*; D001667:Binding, Competitive; D007700:Kinetics; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009561:Nisin / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D001430:Bacteriocins; D008567:Membranes, Artificial; D010455:Peptides; D010713:Phosphatidylcholines; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C057656:gallidermin; D009561:Nisin; D015060:1,2-Dipalmitoylphosphatidylcholine; C017251:1,2-oleoylphosphatidylcholine