Instituto de Agroquímica y Tecnología de Alimentos (IATA), Apartado de Correos 73, Burjassot, E-46100 Valencia, Spain +34 96 3900022 ; +34 96 3636301 ;
Expert Opin Drug Discov. 2009 Jun;4(6):659-71. doi: 10.1517/17460440902992888.
Antimicrobial peptides (AMP) are widely recognized as promising alternatives to the current use of antibiotics and fungicides. Amino-acid sequences of a vast majority of AMP share cationic and amphipathic biophysical properties that allow their insertion into lipid bilayers and can lead to alteration of biological membrane functions. Initial characterization studies linked these properties to antimicrobial killing activity. However, further data indicate that this is not the sole mode of action and that more subtle mechanisms might mediate the interaction with and effect to target microbes, as well as the specificity and toxicity of peptides. As such, AMP are increasingly viewed as powerful multifunctional drugs.
This review summarizes findings on these alternative non-lytic modes of antimicrobial action that go beyond membrane disruption, with an emphasis on the specific interaction with microbial cell wall/membrane components, signaling of AMP exposure and intracellular targets of peptide action. We also explore how novel technologies can help to reveal, characterize and exploit these antimicrobial properties.
Detailed knowledge on non-lytic modes of action of AMP will help in the design and discovery of novel antibacterial and antifungal compounds.
抗菌肽（Antimicrobial peptides，AMP）被广泛认为是替代当前抗生素和杀真菌剂使用的有前途的方法。绝大多数 AMP 的氨基酸序列具有阳离子性和两亲性的生物物理特性，这使其能够插入脂质双分子层，并导致生物膜功能的改变。最初的特性研究将这些特性与抗菌杀伤活性联系起来。然而，进一步的数据表明，这不是唯一的作用模式，更微妙的机制可能介导与靶微生物的相互作用以及肽的特异性和毒性。因此，抗菌肽越来越被视为强大的多功能药物。
本综述总结了这些超越膜破坏的抗菌作用的替代非溶细胞模式的发现，重点是与微生物细胞壁/膜成分的特异性相互作用、抗菌肽暴露的信号转导以及肽作用的细胞内靶点。我们还探讨了新技术如何帮助揭示、表征和利用这些抗菌特性。
对抗菌肽非溶细胞作用模式的详细了解将有助于设计和发现新型的抗细菌和抗真菌化合物。
