Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal.
PLoS One. 2011;6(12):e28549. doi: 10.1371/journal.pone.0028549. Epub 2011 Dec 14.
Consensus is gathering that antimicrobial peptides that exert their antibacterial action at the membrane level must reach a local concentration threshold to become active. Studies of peptide interaction with model membranes do identify such disruptive thresholds but demonstrations of the possible correlation of these with the in vivo onset of activity have only recently been proposed. In addition, such thresholds observed in model membranes occur at local peptide concentrations close to full membrane coverage. In this work we fully develop an interaction model of antimicrobial peptides with biological membranes; by exploring the consequences of the underlying partition formalism we arrive at a relationship that provides antibacterial activity prediction from two biophysical parameters: the affinity of the peptide to the membrane and the critical bound peptide to lipid ratio. A straightforward and robust method to implement this relationship, with potential application to high-throughput screening approaches, is presented and tested. In addition, disruptive thresholds in model membranes and the onset of antibacterial peptide activity are shown to occur over the same range of locally bound peptide concentrations (10 to 100 mM), which conciliates the two types of observations.
人们越来越认为，在膜水平发挥抗菌作用的抗菌肽必须达到局部浓度阈值才能发挥作用。对肽与模型膜相互作用的研究确实确定了这种破坏阈值，但最近才提出了这些阈值与体内活性起始之间可能存在相关性的证明。此外，在模型膜中观察到的这些阈值出现在局部肽浓度接近完全膜覆盖的位置。在这项工作中，我们充分开发了抗菌肽与生物膜相互作用的模型；通过探索基础分区形式主义的后果，我们得到了一个关系，该关系提供了从两个生物物理参数预测抗菌活性的方法：肽与膜的亲和力和临界结合肽与脂质的比率。提出并测试了一种简单而稳健的实现该关系的方法，该方法具有潜在的应用于高通量筛选方法的潜力。此外，模型膜中的破坏阈值和抗菌肽活性的起始都发生在局部结合肽浓度（10 至 100mM）相同的范围内，这调和了这两种观察结果。
