Membrane Lipids Determine the Antibiotic Activity of the Lantibiotic Gallidermin
Membrane Lipids Determine the Antibiotic Activity of the Lantibiotic Gallidermin
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DOI：
10.1007/s00232-008-9134-4
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发表时间：
2008-12-01
影响因子：
2.4
通讯作者：
Bendas, Gerd
中科院分区：
文献类型：
--
作者：
Christ, Katrin;Al-Kaddah, Saad;Bendas, Gerd
羊毛硫抗生素是一组含有羊毛硫氨酸的肽，通过在一个分子内结合不同的杀伤机制来显示其抗生素活性。原型lantibiotic nisin被证明通过与脂质II相互作用而具有肽聚糖合成和细菌膜中孔形成的抑制。Gallidermin与乳链菌肽共享脂质II结合基序，但具有较短的分子长度，在几种细菌菌株中与乳链菌肽的孔形成不同。为了模拟的行动模式，我们采用循环伏安法和石英晶体微天平与模型膜中的gallidermin的脂质II结合动力学的孔形成。Gallidermin不能在DOPC（1，2-二油酰基-sn-甘油-3-磷酸胆碱）（C18/1）和DPoPC（1，2-二棕榈油酰基-sn-甘油-3-磷酸胆碱）（C16/1）膜中形成孔，这与膜厚度有关。为了更好地模拟细菌膜特性，将两种不同的具有支链脂肪酸的磷脂掺入DPoPC基质中。在脂肪酸链的中间具有甲基分支的磷脂有利于通过Gallidermin的脂质II-独立的DPoPC透化，而长分支磷脂，其中分支被放置在亲水区域附近诱导了相同的脂质II-依赖性孔的Gallidermin和乳链菌肽的形成。显然，分支的脂质改变脂质包装和减少膜厚度。因此，gallidermin活性的双重性（孔形成和细胞壁合成的抑制）似乎通过细菌膜组成来平衡。
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.