Developing Antimicrobial Synergy With AMPs.
Developing Antimicrobial Synergy With AMPs.
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DOI：
10.3389/fmedt.2021.640981
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发表时间：
2021
影响因子：
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通讯作者：
Siryaporn A
中科院分区：
文献类型：
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作者：
Duong L;Gross SP;Siryaporn A
抗菌肽（AMP）由于其大量的天然丰度和杀死微生物的能力而被广泛研究。在一个严重缺乏新抗生素的时代，操纵AMP用于治疗应用是一个有前途的选择。然而，对AMP具有抗性的细菌病原体仍然存在问题。为了提高AMP的抗微生物功效，已经提出了它们与其他抗微生物剂联合使用。这是如何工作的？抗菌肽通过在细菌膜上形成孔或抑制细菌大分子功能来杀死细菌。目前尚不清楚的是AMP保持细菌孔开放的持续时间，以及细菌通过修复这些孔可以恢复的程度。在这篇简短的综述中，我们讨论了与AMP的各种抗菌协同作用。如果抗菌剂有助于保持细菌孔开放更长的时间，防止孔修复，在更大的水平上扰乱细菌细胞内功能，或执行其他独立的细菌杀灭机制，则可能产生这种协同作用。我们首先讨论AMP的组合，然后集中于组蛋白，其具有抗微生物活性并与AMP在脂滴和中性粒细胞胞外陷阱（NET）中共定位。最近的工作表明，组蛋白可以增强AMP诱导的膜渗透。组蛋白、组蛋白片段和组蛋白样肽可能会增强抗菌肽的抗菌作用，从而产生抗菌协同作用。如果是这样，阐明这些机制将提高我们对抗菌过程的整体理解，并可能有助于改进药物设计。
Antimicrobial peptides (AMPs) have been extensively studied due to their vast natural abundance and ability to kill microbes. In an era critically lacking in new antibiotics, manipulating AMPs for therapeutic application is a promising option. However, bacterial pathogens resistant to AMPs remain problematic. To improve AMPs antimicrobial efficacy, their use in conjunction with other antimicrobials has been proposed. How might this work? AMPs kill bacteria by forming pores in bacterial membranes or by inhibiting bacterial macromolecular functions. What remains unknown is the duration for which AMPs keep bacterial pores open, and the extent to which bacteria can recover by repairing these pores. In this mini-review, we discuss various antimicrobial synergies with AMPs. Such synergies might arise if the antimicrobial agents helped to keep bacterial pores open for longer periods of time, prevented pore repair, perturbed bacterial intracellular functions at greater levels, or performed other independent bacterial killing mechanisms. We first discuss combinations of AMPs, and then focus on histones, which have antimicrobial activity and co-localize with AMPs on lipid droplets and in neutrophil extracellular traps (NETs). Recent work has demonstrated that histones can enhance AMP-induced membrane permeation. It is possible that histones, histone fragments, and histone-like peptides could amplify the antimicrobial effects of AMPs, giving rise to antimicrobial synergy. If so, clarifying these mechanisms will thus improve our overall understanding of the antimicrobial processes and potentially contribute to improved drug design.