Development of chimeric peptides to facilitate the neutralisation of lipopolysaccharides during bactericidal targeting of multidrug-resistant Escherichia coli

文献类型： 外文期刊

第一作者： Wang, Zhenlong

作者： Wang, Zhenlong;Teng, Da;Mao, Ruoyu;Hao, Ya;Yang, Na;Wang, Xiao;Li, Zhanzhan;Wang, Xiumin;Wang, Jianhua;Wang, Zhenlong;Teng, Da;Mao, Ruoyu;Hao, Ya;Yang, Na;Wang, Xiao;Li, Zhanzhan;Wang, Xiumin;Wang, Jianhua;Liu, Xuehui

作者机构：

期刊名称：COMMUNICATIONS BIOLOGY （ 影响因子：6.268； 五年影响因子：6.268 ）

ISSN：

年卷期： 2020 年 3 卷 1 期

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收录情况： SCI

摘要： Pathogenic Escherichia coli can cause fatal diarrheal diseases in both animals and humans. However, no antibiotics or antimicrobial peptides (AMPs) can adequately kill resistant bacteria and clear bacterial endotoxin, lipopolysaccharide (LPS) which leads to inflammation and sepsis. Here, the LPS-targeted smart chimeric peptides (SCPs)-A6 and G6 are generated by connecting LPS-targeting peptide-LBP14 and killing domain-N6 via different linkers. Rigid and flexible linkers retain the independent biological activities from each component. SCPs-A6 and G6 exert low toxicity and no bacterial resistance, and they more rapidly kill multiple-drug-resistant E. coli and more effectively neutralize LPS toxicity than N6 alone. The SCPs can enhance mouse survival more effectively than N6 or polymyxin B and alleviate lung injuries by blocking mitogen-activated protein kinase and nuclear factor kappa-B p65 activation. These findings uniquely show that SCPs-A6 and G6 may be promising dual-function candidates as improved antibacterial and anti-endotoxin agents to treat bacterial infection and sepsis. Wang ZL and Wang XM design bactericidal peptides in which an antimicrobial domain is fused to a domain that facilitates the neutralisation of lipoplysaccaride (LPS) to prevent inflammation associated with the targeting of Gram-negative bacteria. They characterise their properties and structures, and show their efficiency in vitro and in vivo.

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