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一种用于根除耐甲氧西林金黄色葡萄球菌生物膜和持留菌以减轻抗菌药物耐药性的α/β嵌合肽分子刷。

An alpha/beta chimeric peptide molecular brush for eradicating MRSA biofilms and persister cells to mitigate antimicrobial resistance.

作者信息

Xiao Ximian, Zhang Si, Chen Sheng, Qian Yuxin, Xie Jiayang, Cong Zihao, Zhang Danfeng, Zou Jingcheng, Zhang Wenjing, Ji Zhemin, Cui Ruxin, Qiao Zhongqian, Jiang Weinan, Dai Yidong, Wang Yun, Shao Xiaoyan, Sun Yun, Xia Jiang, Fei Jian, Liu Runhui

机构信息

State Key Laboratory of Bioreactor Engineering, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.

出版信息

Biomater Sci. 2020 Dec 15;8(24):6883-6889. doi: 10.1039/d0bm01211d.

DOI:10.1039/d0bm01211d
PMID:32960197
Abstract

Infections involving methicillin-resistant Staphylococcus aureus present great challenges, especially when biofilms and persister cells are involved. In this work, an α/β chimeric polypeptide molecular brush (α/β CPMB) is reported to show excellent performance in inhibiting the formation of biofilms and eradicating established biofilms. Additionally, the polymer brush efficiently killed metabolically inactive persister cells that are antibiotic-insensitive. Antimicrobial mechanism studies showed that α/β CPMB causes membrane disturbance and a substantial increase in reactive oxygen species (ROS) levels to kill bacteria, and mesosome-like structure formation was also observed. Furthermore, the polymer brush was able to kill clinically isolated multidrug resistant Gram-positive bacteria with no risk of antimicrobial resistance. The α/β CPMB has demonstrated great potential in addressing the great challenge of eradicating multidrug resistant Gram-positive bacterial infections.

摘要

涉及耐甲氧西林金黄色葡萄球菌的感染带来了巨大挑战,尤其是当生物膜和持留菌细胞参与其中时。在这项工作中,据报道一种α/β嵌合多肽分子刷(α/β CPMB)在抑制生物膜形成和根除已形成的生物膜方面表现出优异性能。此外,该聚合物刷能有效杀死对抗生素不敏感的代谢不活跃持留菌细胞。抗菌机制研究表明,α/β CPMB会引起膜扰动并使活性氧(ROS)水平大幅升高以杀死细菌,还观察到了类中间体结构的形成。此外,该聚合物刷能够杀死临床分离的多重耐药革兰氏阳性菌,且不存在产生抗菌耐药性的风险。α/β CPMB在应对根除多重耐药革兰氏阳性菌感染这一巨大挑战方面已展现出巨大潜力。

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