Fatty acid modified-antimicrobial peptide analogues with potent antimicrobial activity and topical therapeutic efficacy against Staphylococcus hyicus

文献类型： 外文期刊

第一作者： Liu, He

作者： Liu, He;Yang, Na;Teng, Da;Mao, Ruoyu;Hao, Ya;Ma, Xuanxuan;Wang, Xiumin;Wang, Jianhua;Liu, He;Yang, Na;Teng, Da;Mao, Ruoyu;Hao, Ya;Ma, Xuanxuan;Wang, Xiumin;Wang, Jianhua

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关键词： Antimicrobial peptides; Fatty acid conjugation; S; hyicus; Topical efficacy

期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：4.813； 五年影响因子：4.697 ）

ISSN： 0175-7598

年卷期： 2021 年 105 卷 14-15 期

页码：

收录情况： SCI

摘要： There is an urgent need to explore new antimicrobial agents due to the looming threat of bacteria resistance. Bovine lactoferricin (LfcinB), as a multifunctional peptide, has the potential to be a new active drug in the future. In this study, it aims to investigate the effect of fatty acid conjugation on antimicrobial peptide activity and topical therapeutic efficacy in a mouse model infected with Staphylococcus hyicus. Both Lfcin4 and Lfcin5 were conjugated with the unsaturated fatty acid linoleic acid (18-C) at their N-terminus and modified by acylation at the C-terminus. The derived peptides of Lin-Lf4NH2 and Lin-Lf5NH2 showed better antibacterial activity (MICs of 3.27 to 6.64 mu M) than their parent peptides (MICs of 1.83 to 59.57 mu M). Lin-Lf4NH2 (63.2%, 5 min) and Lin-Lf5NH2 (35.8%, 5 min) could more rapidly penetrate bacterial membrane than Lf4NH2 (2.34%, 5 min) and Lf5NH2 (1.94%, 5 min), which further confirmed by the laser scanning confocal microscopy (LSCM). Electron microscopy observations showed Lin-Lf4NH2 and Lin-Lf5NH2 disrupted S. hyicus cell membranes and led to the leakage of contents. Furthermore, after treatment with Lin-Lf4NH2 and Lin-Lf5NH2, the abscess symptoms of mice were significantly alleviated; the recovery rate of abscesses scope of Lin-Lf4NH2 (73.25%) and Lin-Lf5NH2 (71.71%) were 38.8 and 37.9-fold higher than that of untreated group (1.89%), respectively, and superior to Lf4NH2 (46.87%) and Lf5NH2 (58.75%). They significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines (TNF-alpha, IL-6, and IL-1 beta) and chemokine (MCP-1) in S. hyicus skin lesions. This study provides evidence that conjugation of a fatty acid to antimicrobial peptides can improve the activity and have potential for topical therapeutic of S. hyicus skin infections.

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