Dennison Sarah R, Morton Leslie H G, Harris Frederick, Phoenix David A
Faculty of Science and Technology, University of Central Lancashire, Preston PR1 2HE, UK.
Chem Phys Lipids. 2008 Feb;151(2):92-102. doi: 10.1016/j.chemphyslip.2007.10.007. Epub 2007 Nov 17.
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.
VP1是一种假定的α-螺旋抗菌肽（α-AMP），在500微摩尔浓度时可抑制枯草芽孢杆菌和大肠杆菌的生长。该肽在由枯草芽孢杆菌天然脂质提取物形成的单层膜中引起稳定的表面压力变化（约4.5毫牛顿/米），但在相应的大肠杆菌单层膜中引起短暂的压力变化（约1.0毫牛顿/米），这导致单层膜解体。使用模拟提取物的合成脂质单层膜来生成压缩等温线。枯草芽孢杆菌等温线的热力学分析表明，VP1通过一种依赖于磷脂酰甘油与心磷脂比例的机制使膜稳定（混合自由能<0）。大肠杆菌等温线的相应分析表明该肽使膜不稳定（混合自由能>０）。不稳定与存在的磷脂酰乙醇胺水平相关，并且似乎涉及一种类似于倾斜肽所使用的机制。这些数据强调，α-AMPs的结构/功能分析不仅必须考虑其结构特征，还必须考虑目标微生物膜的脂质组成。
