Antimicrobial peptides (AMPs) are promising candidates for anti-infective drugs. The majority of AMPs are considered to disrupt the lipid matrix of bacterial membranes, exerting bactericidal activity. A number of biophysical studies have been carried out to elucidate the underlying molecular mechanisms. However, the fact that the number of peptide molecules bound to a bacterial cell under bactericidal conditions is much larger than that expected from liposomal studies raises the question of whether membrane permeabilization mechanisms proposed by liposomal studies are relevant to bacteria. In this study, the peptide-to-lipid molar ratio needed for an antimicrobial magainin peptide to permeabilize the cell membrane of the Gram-positive bacterium Bacillus megaterium was estimated by random fluorescence resonance energy transfer from a BODIPY FL-labeled lipid to a Texas Red-labeled peptide. The comparison of the observed energy transfer efficiency with the two-dimensional energy transfer theory estimated that the leakage of the calcein dye from bacterial cells occurred at a peptide-to-lipid molar ratio of 0.025. At this ratio, the peptide induced dye leakage from liposomes mimicking the bacterial membrane, indicating that the lipid matrix is a target of membrane-acting AMPs and that liposomes are a useful model system to investigate their mechanisms of action. Furthermore, a binding assay suggested that most peptide molecules were bound to cellular components other than cell membranes.

中文翻译：

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细胞内 FRET 表明 Magainin 肽在与脂质体研究相关的较低肽与脂质比率下诱导细菌细胞膜的透化

抗微生物肽 (AMP) 是抗感染药物的有希望的候选者。大多数 AMP 被认为会破坏细菌膜的脂质基质，发挥杀菌活性。已经进行了许多生物物理学研究以阐明潜在的分子机制。然而，在杀菌条件下与细菌细胞结合的肽分子数量远大于脂质体研究的预期这一事实提出了脂质体研究提出的膜透化机制是否与细菌相关的问题。在这项研究中，抗菌 magainin 肽使革兰氏阳性细菌巨大芽孢杆菌的细胞膜通透所需的肽与脂质摩尔比通过从 BODIPY FL 标记的脂质到德克萨斯红标记的肽的随机荧光共振能量转移来估计。将观察到的能量转移效率与二维能量转移理论进行比较，估计细菌细胞中钙黄绿素染料的泄漏发生在肽与脂质的摩尔比为 0.025 时。在这个比例下，肽诱导染料从模拟细菌膜的脂质体中泄漏，表明脂质基质是膜作用 AMP 的目标，并且脂质体是研究其作用机制的有用模型系统。此外，结合测定表明大多数肽分子与细胞膜以外的细胞成分结合。