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Unnatural Amino-Acid-Based Star-Shaped Poly(l-Ornithine)s as Emerging Long-Term and Biofilm-Disrupting Antimicrobial Peptides to Treat Pseudomonas aeruginosa-Infected Burn Wounds.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-09-06 , DOI: 10.1002/adhm.202000647
Miao Pan 1 , Chao Lu 2, 3 , Maochao Zheng 1 , Wen Zhou 1 , Fuling Song 1 , Weidong Chen 1 , Fen Yao 1 , Daojun Liu 1 , Jianfeng Cai 3
Affiliation  

Peptide‐based antimicrobial materials are recognized as promising alternatives to antibiotics to circumvent the emergence of antibiotic‐resistant bacteria or to combat multiple resistant bacteria by targeting the bacterial cell membrane. The components and conformations of antimicrobial peptides are extensively explored to achieve broad‐spectrum and effective antimicrobial activity. Here, star‐shaped antimicrobial polypeptides are fabricated by employing homologs of poly(l‐lysine)s (i.e., poly(l‐ornithine)s, poly(l‐lysine)s, and poly(lα,ζ‐diaminoheptylic acid)s) with the aim of modulating their charge/hydrophobicity balance and rationalizing their structure–antimicrobial property relationships. The in vitro antibacterial investigation reveals that unnatural amino‐acid‐based star‐shaped poly(l‐ornithine)s have remarkable proteolytic stability, excellent biofilm‐disrupting capacity, and broad‐spectrum antimicrobial activity, even against difficult‐to‐kill Gram‐negative Pseudomonas aeruginosa. Furthermore, star‐shaped poly(l‐ornithine)s significantly reduce the microbial burden and improve the burn wound healing of mouse skin infected with P. aeruginosa. These results demonstrate that unnatural amino‐acid‐based star‐shaped poly(l‐ornithine)s can serve as emerging long‐term and biofilm‐disrupting antimicrobial agents to treat biofilm‐related infections in burn, especially caused by notorious P. aeruginosa.

中文翻译:

基于非天然氨基酸的星形聚(l-鸟氨酸)作为新兴的长期和破坏生物膜的抗菌肽治疗铜绿假单胞菌感染的烧伤。

基于肽的抗菌材料被认为是抗生素的有希望的替代品,可以通过靶向细菌细胞膜来规避抗生素耐药细菌的出现或对抗多种耐药细菌。广泛探索抗菌肽的成分和构象以实现广谱和有效的抗菌活性。在这里,星形抗菌多肽是通过使用多聚(L-赖氨酸)的同系物(即多聚(L-鸟氨酸)、多聚( L-赖氨酸)和多聚(L - αζ )来制造的。-二氨基庚酸),目的是调节它们的电荷/疏水性平衡并合理化它们的结构-抗菌性能关系。体外抗菌研究表明,基于非天然氨基酸的星形聚(L-鸟氨酸)具有显着的蛋白水解稳定性、优异的生物膜破坏能力和广谱抗菌活性,甚至对难以杀死的革兰氏阴性铜绿假单胞菌。此外,星形聚(L-鸟氨酸)显着降低了微生物负荷,改善了感染铜绿假单胞菌的小鼠皮肤烧伤伤口的愈合。这些结果表明,基于非天然氨基酸的星形聚(l-鸟氨酸)可以作为新兴的长期和破坏生物膜的抗菌剂,用于治疗烧伤中与生物膜相关的感染,尤其是由臭名昭著的铜绿假单胞菌引起的感染。
更新日期:2020-10-07
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