Acta Biomaterialia ( IF 9.4 ) Pub Date : 2023-02-17 , DOI: 10.1016/j.actbio.2023.02.017 Wei Zhou 1 , Ge Shi 2 , Peng Zhao 1 , Gai Zhang 3 , Peilang Yang 3 , Bohan Li 1 , Bowen Li 4 , Xinhua Wan 4 , Yijun Zheng 1
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The antimicrobial activity of native antimicrobial peptides (AMPs) is often attributed to their helical structure, but the effectiveness of synthetic mimics with dynamic helical conformations, such as antimicrobial cationic polymers (ACPs), has not been well studied. Herein we demonstrate the antimicrobial activity of pyrrolidinium-pendant polyacetylenes (PAs) with dynamic helical conformations. The PAs exhibit fast and efficient antimicrobial activity against a wide range of pathogens, with low toxicity to mammalian cells and minimal risk of antibiotic resistance. In addition, the full-thickness wound infection model in mice has demonstrated the favorable biocompatibility and effective in vivo antibacterial capabilities of these PAs. Our data suggest that the dynamic helical structure of these PAs allows them to adapt and form pores in the bacterial membrane upon interaction, leading to their potent antimicrobial activity. This work investigated the antibacterial mechanism of dynamic helical ACPs, which provides valuable guidance for the rational design of high-performance antimicrobial agents.
Statement of significance
Our study represents a significant contribution to the literature on antimicrobial cationic polymers (ACPs) as alternatives to antibiotics. Through a systematic investigation of the role of dynamic helical conformation in polyacetylenes (PAs) and the use of PAs with adaptive structure for the first time, we have provided valuable insights into the bacterial membrane action and killing mechanisms of these polymers. The results of our study, including fast killing rates and minimum inhibitory concentrations as low as 4–16 µg/mL against a broad range of pathogens and strong in vivo antibacterial activity, demonstrate the potential of these ACPs as high-performance antimicrobials. Our findings may guide the design of future ACPs with enhanced antimicrobial activity.
中文翻译：
动态螺旋阳离子聚乙炔快速高效杀灭细菌
天然抗菌肽(AMP)的抗菌活性通常归因于它们的螺旋结构，但具有动态螺旋构象的合成模拟物（例如抗菌阳离子聚合物 (ACP)）的有效性尚未得到很好的研究。在这里，我们展示了具有动态螺旋构象的吡咯烷悬垂聚乙炔 (PA) 的抗菌活性。PA 对多种病原体表现出快速有效的抗菌活性，对哺乳动物细胞毒性低，抗生素耐药性风险最小. 此外，小鼠全层伤口感染模型证明了这些 PA 具有良好的生物相容性和有效的体内抗菌能力。我们的数据表明，这些 PA 的动态螺旋结构允许它们在相互作用时适应并在细菌膜中形成孔隙，从而导致它们具有强大的抗菌活性。该工作探究了动态螺旋ACPs的抗菌机制，为合理设计高性能抗菌剂提供了有价值的指导。
重要性声明
我们的研究对有关抗菌阳离子聚合物 (ACP) 作为抗生素替代品的文献做出了重大贡献。通过系统研究动态螺旋构象在聚乙炔 (PA) 中的作用以及首次使用具有适应性结构的 PA，我们对这些聚合物的细菌膜作用和杀灭机制提供了有价值的见解。我们的研究结果，包括对广泛病原体的快速杀灭率和低至 4-16 µg/mL 的最低抑制浓度以及强大的体内抗菌活性，证明了这些 ACPs 作为高性能抗菌剂的潜力。我们的研究结果可能会指导未来具有增强抗菌活性的 ACP 的设计。
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