Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autonoma de Barcelona, Cerdanyola del Valles, Spain.
Curr Top Med Chem. 2020;20(14):1238-1263. doi: 10.2174/1568026620666200303122626.
Antimicrobial resistance (AMR) to conventional antibiotics is becoming one of the main global health threats and novel alternative strategies are urging. Antimicrobial peptides (AMPs), once forgotten, are coming back into the scene as promising tools to overcome bacterial resistance. Recent findings have attracted attention to the potentiality of AMPs to work as antibiotic adjuvants.
In this review, we have tried to collect the currently available information on the mechanism of action of AMPs in synergy with other antimicrobial agents. In particular, we have focused on the mechanisms of action that mediate the inhibition of the emergence of bacterial resistance by AMPs.
We find in the literature many examples where AMPs can significantly reduce the antibiotic effective concentration. Mainly, the peptides work at the bacterial cell wall and thereby facilitate the drug access to its intracellular target. Complementarily, AMPs can also contribute to permeate the exopolysaccharide layer of biofilm communities, or even prevent bacterial adhesion and biofilm growth. Secondly, we find other peptides that can directly block the emergence of bacterial resistance mechanisms or interfere with the community quorum-sensing systems. Interestingly, the effective peptide concentrations for adjuvant activity and inhibition of bacterial resistance are much lower than the required for direct antimicrobial action. Finally, many AMPs expressed by innate immune cells are endowed with immunomodulatory properties and can participate in the host response against infection. Recent studies in animal models confirm that AMPs work as adjuvants at non-toxic concentrations and can be safely administrated for novel combined chemotherapies.
传统抗生素的抗药性（AMR）正成为全球主要健康威胁之一，因此迫切需要新的替代策略。抗菌肽（AMPs）曾一度被忽视，如今作为克服细菌耐药性的有前途的工具重新受到关注。最近的研究结果引起了人们对 AMP 作为抗生素佐剂的潜力的关注。
在这篇综述中，我们试图收集目前关于 AMP 与其他抗菌剂协同作用的作用机制的可用信息。特别是，我们重点关注介导 AMP 抑制细菌耐药性出现的作用机制。
我们在文献中发现了许多例子，其中 AMP 可以显著降低抗生素的有效浓度。主要是，这些肽作用于细菌细胞壁，从而促进药物进入其细胞内靶标。此外，AMP 还可以渗透生物膜群落的胞外多糖层，甚至可以防止细菌黏附和生物膜生长。其次，我们还发现了其他一些可以直接阻断细菌耐药机制的出现或干扰群体感应系统的肽。有趣的是，用于佐剂活性和抑制细菌耐药性的有效肽浓度远低于直接抗菌作用所需的浓度。最后，先天免疫细胞表达的许多 AMP 具有免疫调节特性，可以参与宿主对感染的反应。最近在动物模型中的研究证实，AMP 以非毒性浓度作为佐剂发挥作用，可以安全地用于新型联合化疗。
