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用于病原体特异性识别和根除以治疗肠炎的超分子开关介导的群体感应陷阱

Supramolecular Switching-Enabled Quorum Sensing Trap for Pathogen-Specific Recognition and Eradication to Treat Enteritis.

作者信息

Wu Xiaojie, Borjihan Qinggele, Su Yueying, Bai Haoran, Hu Xinshang, Wang Xin, Kang Jing, Dong Alideertu, Yang Ying-Wei

机构信息

College of Chemistry and Chemical Engineering, Engineering Research Center of Dairy Quality and Safety Control Technology, Ministry of Education, Inner Mongolia University, 235 Daxue West Road, Hohhot 010021, P. R. China.

Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, 306 Zhaowuda Road, Hohhot 010018, Inner Mongolia, P. R. China.

出版信息

J Am Chem Soc. 2024 Dec 25;146(51):35402-35415. doi: 10.1021/jacs.4c14424. Epub 2024 Dec 12.

DOI:10.1021/jacs.4c14424
PMID:39665393
Abstract

Intestinal bacterial infections have become a significant threat to human health. However, the current typical antibiotic-based therapies not only contribute to drug resistance but also disrupt gut microbiota balance, resulting in additional adverse effects on life activities. There is an urgent need to develop new antibacterial materials that selectively eliminate pathogenic bacteria without disrupting beneficial bacterial communities or promoting drug resistance. Herein, we utilize bacterial quorum sensing (QS), a universal mechanism for regulating community behavior, to develop a supramolecular QS trap by encapsulating cucurbit[7]uril (CB[7]) on 1-vinyl-3-pentylimidazolium bromide ([VPIM]Br) to form a supramolecular switch ([VPIM]Br⊂CB[7]) through host-guest interactions followed by grafting it onto bacterial cell surfaces using atom transfer radical polymerization. Subsequently, the matched pathogens are recognized and aggregated through interbacterial QS signals. Furthermore, the addition of amantadine (AD) facilitates the release of [VPIM]Br by competitive binding of CB[7] on [VPIM]Br⊂CB[7] for sterilization. This QS trap specifically triggers the self-aggregation and efficient elimination of matched bacteria. The [VPIM]Br⊂CB[7]-based trap can increase the diversity and abundance of intestinal microorganisms in mice, effectively treating K88-induced intestinal damage without perturbing gut microbiota balance. This supramolecular-switched QS trap opens up a promising avenue to specifically recognize and eradicate pathogens for the antibiotic-free treatment of intestinal bacterial infections and other inflammatory diseases.

摘要

肠道细菌感染已对人类健康构成重大威胁。然而,当前典型的基于抗生素的疗法不仅会导致耐药性,还会破坏肠道微生物群平衡,对生命活动产生额外的不良影响。迫切需要开发新的抗菌材料,能够选择性地消除病原菌,而不破坏有益细菌群落或促进耐药性。在此,我们利用细菌群体感应(QS)这一调节群落行为的通用机制,通过将葫芦[7]脲(CB[7])包裹在1-乙烯基-3-戊基咪唑溴盐([VPIM]Br)上,通过主客体相互作用形成超分子开关([VPIM]Br⊂CB[7]),随后利用原子转移自由基聚合将其接枝到细菌细胞表面,从而开发出一种超分子QS陷阱。随后,通过细菌间的QS信号识别并聚集匹配的病原体。此外,加入金刚烷胺(AD)通过CB[7]与[VPIM]Br⊂CB[7]上的[VPIM]Br竞争性结合促进[VPIM]Br的释放以进行杀菌。这种QS陷阱特异性地触发匹配细菌的自聚集和有效消除。基于[VPIM]Br⊂CB[7]的陷阱可以增加小鼠肠道微生物的多样性和丰度,有效治疗K88诱导的肠道损伤而不扰乱肠道微生物群平衡。这种超分子开关式QS陷阱为特异性识别和根除病原体开辟了一条有前途的途径,用于肠道细菌感染和其他炎症性疾病的无抗生素治疗。

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