A cleavable chimeric peptide with targeting and killing domains enhances LPS neutralization and antibacterial properties against multi-drug resistant E. 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, Xiumin;Wang, Jianhua;Wang, Zhenlong;Teng, Da;Mao, Ruoyu;Hao, Ya;Yang, Na;Wang, Xiumin;Wang, Jianhua

作者机构:

期刊名称:COMMUNICATIONS BIOLOGY ( 影响因子:5.9; 五年影响因子:6.3 )

ISSN:

年卷期: 2023 年 6 卷 1 期

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收录情况: SCI

摘要: Pathogenic Escherichia coli is one of the most common causes of diarrhea diseases and its characteristic component of the outer membrane-lipopolysaccharide (LPS) is a major inducer of sepsis. Few drugs have been proven to kill bacteria and simultaneously neutralize LPS toxicity. Here, the chimeric peptides-R7, A7 and G7 were generated by connecting LBP14 (LPS-targeting domain) with L7 (killing domain) via different linkers to improve antibacterial and anti-inflammatory activities. Compared to parent LBP14-RKRR and L7, the antibacterial activity of R7 with a cleavable "RKRR" linker and the "LBP14-RKRR+L7" cocktail against Escherichia coli, Salmonella typhimurium and Staphylococcus aureus was increased by 2 similar to 4-fold. Both A7 and G7 with non-cleavable linkers almost lost antibacterial activity. The ability of R7 to neutralize LPS was markedly higher than that of LBP14-RKRR and L7. In vivo, R7 could be cleaved by furin in a time-dependent manner, and release L7 and LBP14-RKRR in serum. In vivo, R7 can enhance mouse survival more effectively than L7 and alleviate lung injuries by selective inhibition of the NF-kappa B signaling pathways and promoting higher IAP activity. It suggests that R7 may be promising dual-function candidates as antibacterial and anti-endotoxin agents. Characterisation of an antibacterial peptide able to both enhance LPS neutralization and neutralise multidrug-resistant E.coli.

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