Short linear antimicrobial peptides are attractive templates for developing new antibiotics. Here, it is described a study of the interaction between two short Trp-rich peptides, horine and verine-L, and model membranes. Isothermal titration calorimetry studies showed that the affinity of these peptides towards large unilamellar vesicles (LUV) having a lipid composition mimicking the lipid composition of S. aureus membranes is ca. 30-fold higher than that towards E. coli mimetics. The former interaction is driven by enthalpy and entropy, while the latter case is driven by entropy, suggesting differences in the forces that play a role in the binding to the two types of model membranes. Upon membrane binding the peptides acquired different conformations according to circular dichroism (CD) studies; however, in both cases CD studies indicated stacked W-residues. Peptide-induced membrane permeabilization, lipid flip-flop, molecular packing at the membrane-water interface, and lateral lipid segregation were observed in all cases. However, the extent of these peptide-induced changes on membrane properties was always higher in S. aureus than E. coli mimetics. Both peptides seem to act via a similar mechanism of membrane permeabilization of S. aureus membrane mimetics, while their mechanisms seem to differ in the case of E. coli. This may be the result of differences in both the peptides´ structure and the membrane lipid composition between both types of bacteria.

中文翻译：

---

两种富含Trp的两亲性短肽的膜活性。

短线性抗菌肽是开发新抗生素的有吸引力的模板。在这里，它描述了两种短的富含Trp的肽，尿液和verine-L与模型膜之间相互作用的研究。等温滴定量热法研究表明，这些肽对具有模拟金黄色葡萄球菌膜脂质组成的脂质组成的大单层囊泡（LUV）的亲和力约为。比模拟大肠杆菌高30倍。前者的相互作用是由焓和熵驱动的，而后者的情况是由熵驱动的，这表明在与两种类型的模型膜结合中起作用的力的差异。膜结合后，根据圆二色性（CD）研究，这些肽获得了不同的构象；然而，在这两种情况下，CD研究均显示堆积的W残基。在所有情况下均观察到肽诱导的膜通透性，脂质翻转，膜-水界面处的分子堆积以及脂质的侧向分离。然而，这些肽诱导的膜性质变化的程度在金黄色葡萄球菌中总是比大肠杆菌模拟物更高。两种肽似乎都通过金黄色葡萄球菌膜模拟物的膜透化相似机制起作用，而在大肠杆菌中它们的机制似乎不同。这可能是两种细菌之间的肽结构和膜脂质组成不同的结果。这些肽诱导的膜性质变化的程度在金黄色葡萄球菌中总是比大肠杆菌模拟物高。两种肽似乎都通过金黄色葡萄球菌膜模拟物的膜透化相似机制起作用，而在大肠杆菌中它们的机制似乎有所不同。这可能是两种细菌之间的肽结构和膜脂质组成不同的结果。这些肽诱导的膜性质变化的程度在金黄色葡萄球菌中总是比大肠杆菌模拟物高。两种肽似乎都通过金黄色葡萄球菌膜模拟物的膜透化相似机制起作用，而在大肠杆菌中它们的机制似乎有所不同。这可能是两种细菌之间的肽结构和膜脂质组成不同的结果。