Model membrane studies for characterization of different antibiotic activities of lipopeptides from Pseudomonas.
Model membrane studies for characterization of different antibiotic activities of lipopeptides from Pseudomonas.
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假单胞菌脂肽不同抗生素活性表征的模型膜研究
DOI：
10.1016/j.bbamem.2011.08.007
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Bendas
中科院分区：
文献类型：
--
作者：
Reder-Christ;Schmidt;Josten;Raaijmakers;Bendas
脂肽（LPs）是一类结构多样的两亲性天然产物，过去主要以其表面活性剂特性而闻名。然而，最近发现的它们的抗菌和细胞毒性生物活性已经点燃并重新燃起了对这类化合物的兴趣。在这类化合物的抗菌潜力的推动下，本研究对来自假单胞菌的六种未被充分研究的LPs进行了对细菌的抗生素活性研究。结果表明，由SH-C52假单胞菌产生的糖基化脂二肽SB-253514具有明显的抑菌活性。由于脂多糖的生物活性通常归因于膜相互作用，我们通过互补的生物物理方法更详细地分析了脂多糖和细菌样脂质模型膜之间的分子相互作用。石英晶体微天平（QCM）的应用表明，所有LPs对模型膜具有高的结合亲和力。尽管它们具有相似的膜亲和性，但单层研究显示，LPs融入膜的倾向不同。膜的掺入程度可能与所研究的LPs的特定结构特征有关，如肽大环与脂肪酸之间的距离，但不能完全反映它们各自的抗菌活性。循环伏安法（CV）实验进一步证实了SB-253514在抑制浓度下没有膜透性作用。总的来说，这些结果表明SB-253514的抗菌活性不能用一种非特异性的类似洗涤剂的机制来解释，这种机制通常是针对两亲分子提出的，而是通过一个确定的结构靶标来解释的。
Lipopeptides (LPs) are a structurally diverse class of amphipathic natural products that were in the past mainly known for their surfactant properties. However, the recent discovery of their antimicrobial and cytotoxic bioactivities have fueled and renewed the interest in this compound class. Propelled by the antimicrobial potential of this compound class, in this study a range of six underinvestigated LPs from Pseudomonads were examined with respect to their antibiotic activities towards bacteria. The assays revealed that only the glycosylated lipodipeptide SB-253514, produced by Pseudomonas strain SH-C52, showed significant antibacterial activity. Since the bioactivity of LPs is commonly attributed to membrane interactions, we analyzed the molecular interactions between the LPs and bacteria-like lipid model membranes in more detail via complementary biophysical approaches. Application of the quartz crystal microbalance (QCM) showed that all LPs possess a high binding affinity towards the model membranes. Despite their similar membrane affinity, monolayer studies displayed different tendencies of LPs to incorporate into the membrane. The degree of membrane incorporation could be correlated with specific structural features of the investigated LPs, such as distance between the peptidic macrocycle and the fatty acid, but did not fully reflect their respective antibacterial activity. Cyclic voltammetry (CV) experiments further demonstrated that SB-253514 showed no membrane permeabilization effects at inhibitory concentrations. Collectively, these results suggests that the antibacterial activity of SB-253514 cannot be explained by an unspecific detergent-like mechanism generally proposed for amphiphilic molecules but instead appears to occur via a defined structural target.
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影响因子：
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作者：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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作者：
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