Alvares Dayane S, Viegas Taisa Giordano, Ruggiero Neto João
Department of Physics, UNESP - São Paulo State University, IBILCE, R. Cristóvão Colombo, 2265, São José do Rio Preto, SP, CEP 15054-000, Brazil.
Biophys Rev. 2017 Oct;9(5):669-682. doi: 10.1007/s12551-017-0296-0. Epub 2017 Aug 29.
The indiscriminate use of conventional antibiotics is leading to an increase in the number of resistant bacterial strains, motivating the search for new compounds to overcome this challenging problem. Antimicrobial peptides, acting only in the lipid phase of membranes without requiring specific membrane receptors as do conventional antibiotics, have shown great potential as possible substituents of these drugs. These peptides are in general rich in basic and hydrophobic residues forming an amphipathic structure when in contact with membranes. The outer leaflet of the prokaryotic cell membrane is rich in anionic lipids, while the surface of the eukaryotic cell is zwitterionic. Due to their positive net charge, many of these peptides are selective to the prokaryotic membrane. Notwithstanding this preference for anionic membranes, some of them can also act on neutral ones, hampering their therapeutic use. In addition to the electrostatic interaction driving peptide adsorption by the membrane, the ability of the peptide to perturb lipid packing is of paramount importance in their capacity to induce cell lysis, which is strongly dependent on electrostatic and hydrophobic interactions. In the present research, we revised the adsorption of antimicrobial peptides by model membranes as well as the perturbation that they induce in lipid packing. In particular, we focused on some peptides that have simultaneously acidic and basic residues. The net charges of these peptides are modulated by pH changes and the lipid composition of model membranes. We discuss the experimental approaches used to explore these aspects of lipid membranes using lipid vesicles and lipid monolayer as model membranes.
常规抗生素的滥用导致耐药细菌菌株数量增加，促使人们寻找新的化合物来克服这一具有挑战性的问题。抗菌肽仅在膜的脂质相中起作用，不像常规抗生素那样需要特定的膜受体，已显示出作为这些药物可能替代物的巨大潜力。这些肽通常富含碱性和疏水残基，与膜接触时形成两亲结构。原核细胞膜的外小叶富含阴离子脂质，而真核细胞表面是两性离子的。由于它们带正净电荷，这些肽中的许多对原核膜具有选择性。尽管对阴离子膜有这种偏好，但其中一些也可作用于中性膜，这妨碍了它们的治疗用途。除了静电相互作用驱动肽被膜吸附外，肽扰乱脂质堆积的能力对其诱导细胞裂解的能力至关重要，这强烈依赖于静电和疏水相互作用。在本研究中，我们修订了抗菌肽在模型膜上的吸附以及它们在脂质堆积中引起的扰动。特别是，我们关注了一些同时具有酸性和碱性残基的肽。这些肽的净电荷受pH变化和模型膜的脂质组成调节。我们讨论了使用脂质囊泡和脂质单层作为模型膜来探索脂质膜这些方面的实验方法。
