The impact of membrane lipid composition on antimicrobial function of an alpha-helical peptide.
VP1, a putative alpha-helical antimicrobial peptide (alpha-AMP) inhibited growth of Bacillus subtilis and Escherichia coli at 500microM. The peptide induced stable surface pressure changes in monolayers formed from B. subtilis native lipid extract (circa 4.5mNm(-1)) but transient pressure changes in corresponding E. coli monolayers (circa 1.0mNm(-1)), which led to monolayer disintegration. Synthetic lipid monolayers mimetic of the extracts were used to generate compression isotherms. Thermodynamic analysis of B. subtilis isotherms indicated membrane stabilisation by VP1 (DeltaG(Mix)<0), via a mechanism dependent upon the phosphatidylglycerol to cardiolipin ratio. Corresponding analysis of E. coli isotherms indicated membrane destabilisation by the peptide (DeltaG(Mix)>0). Destabilisation correlated with PE levels present and appeared to involve a mechanism resembling those used by tilted peptides. These data emphasise that structure/function analysis of alpha-AMPs must consider not only their structural characteristics but also the lipid make-up of the target microbial membrane.
Faculty of Science and Technology, University of Central Lancashire, Preston PR1 2HE, UK.
Sarah R
SR
Dennison
Leslie H G
LH
Morton
Frederick
F
Harris
David A
DA
Phoenix
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000737:chemistry / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects; D008563:Membrane Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011312:Pressure; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D008563:Membrane Lipids; D009842:Oligopeptides; C523526:glycyl-threonyl-alanyl-methionyl-arginyl-isoleucyl-leucyl-glycyl-glycyl-valyl-isoleucine