Antimicrobial peptides (AMPs) have great potential in treating multi-drug resistant bacterial infections. The antimicrobial activity of d-enantiomers is significantly higher than l-enantiomers and sometimes selectively enhanced against Gram-positive bacteria. Unlike phospholipids in the bacterial plasma membrane, the role of other bacterial cell envelop components is often overlooked in the mode of action of AMPs. In this work, we explored the structural interactions between the main different structural components in Gram-negative/Gram-positive bacteria and the two enantiomers of a designer AMP, GL13K. We observed that both l-GL13K and d-GL13K formed self-assembled amyloid-like nanofibrils when the peptides interacted with lipopolysaccharide and lipoteichoic acid, components of the outer membrane of Gram-negative bacteria and cell wall of Gram-positive bacteria, respectively. Another cell wall component, peptidoglycan, showed strong interactions exclusively with d-GL13K and formed distinct laminar structures. This specific interaction between peptidoglycans and d-GL13K might contribute to the enhanced activity of d-GL13K against Gram-positive bacteria as they have a much thicker peptidoglycan layer than Gram-negative bacteria. A better understanding of the specific role of bacterial cell envelop components in the AMPs mechanism of action can guide the design of more effective Gram-selective AMPs.

中文翻译：

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设计抗菌肽的两种对映体与细菌细胞包膜结构成分的相互作用

抗菌肽 (AMP) 在治疗多重耐药细菌感染方面具有巨大潜力。d-对映体的抗菌活性明显高于l-对映体，有时选择性地增强对革兰氏阳性菌的抗菌活性。与细菌质膜中的磷脂不同，其他细菌细胞膜成分的作用在 AMP 的作用模式中经常被忽视。在这项工作中，我们探索了革兰氏阴性/革兰氏阳性细菌中主要不同结构成分与设计师 AMP GL13K 的两种对映体之间的结构相互作用。我们观察到l -GL13K 和d-当多肽与脂多糖和脂磷壁酸相互作用时，GL13K 形成自组装的淀粉样蛋白样纳米纤维，脂多糖和脂磷壁酸分别是革兰氏阴性菌外膜和革兰氏阳性菌细胞壁的成分。另一种细胞壁成分，肽聚糖，仅与d -GL13K 表现出强烈的相互作用，并形成独特的层状结构。肽聚糖和d -GL13K之间的这种特定相互作用可能有助于增强d的活性-GL13K 对抗革兰氏阳性菌，因为它们的肽聚糖层比革兰氏阴性菌厚得多。更好地了解细菌细胞包膜成分在 AMP 作用机制中的具体作用可以指导设计更有效的革兰氏选择性 AMP。