Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design.
Membrane Active Antimicrobial Peptides: Translating Mechanistic Insights to Design.
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DOI：
10.3389/fnins.2017.00073
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发表时间：
2017
影响因子：
4.3
通讯作者：
Beuerman RW
中科院分区：
文献类型：
--
作者：
Li J;Koh JJ;Liu S;Lakshminarayanan R;Verma CS;Beuerman RW
抗菌肽（Antimicrobial peptides，AMP）是新一代的抗生素，在对抗细菌耐药性方面具有巨大的潜力。AMP可以是抑菌和杀菌的，诱导快速杀灭，并且显示出比常规抗生素更低的产生耐药性的倾向。尽管在过去的30年里取得了重大进展，但还没有肽抗生素进入临床。对作用机理的认识不足和缺乏合理的设计原则是阻碍进展的两大障碍。技术的发展现在使多学科的方法，包括分子动力学模拟结合生物物理学和微生物学提供有价值的见解AMP与膜在原子水平上的相互作用。这导致AMP作用机制的模型越来越强大，并开始为发现新的AMP做出有意义的贡献。这篇综述讨论了已经提出的详细的作用机制，详细的原子论的见解AMP如何与细菌膜相互作用。审查进一步讨论了如何利用这方面的知识对开发新的AMP的设计原则。最后，AMP治疗的发展现状，相关的挑战和未来的方向进行了讨论。
Antimicrobial peptides (AMPs) are promising next generation antibiotics that hold great potential for combating bacterial resistance. AMPs can be both bacteriostatic and bactericidal, induce rapid killing and display a lower propensity to develop resistance than do conventional antibiotics. Despite significant progress in the past 30 years, no peptide antibiotic has reached the clinic yet. Poor understanding of the action mechanisms and lack of rational design principles have been the two major obstacles that have slowed progress. Technological developments are now enabling multidisciplinary approaches including molecular dynamics simulations combined with biophysics and microbiology toward providing valuable insights into the interactions of AMPs with membranes at atomic level. This has led to increasingly robust models of the mechanisms of action of AMPs and has begun to contribute meaningfully toward the discovery of new AMPs. This review discusses the detailed action mechanisms that have been put forward, with detailed atomistic insights into how the AMPs interact with bacterial membranes. The review further discusses how this knowledge is exploited toward developing design principles for novel AMPs. Finally, the current status, associated challenges, and future directions for the development of AMP therapeutics are discussed.