Killing of Staphylococcus aureus and Salmonella enteritidis and neutralization of lipopolysaccharide by 17-residue bovine lactoferricins: improved activity of Trp/Ala-containing molecules

文献类型： 外文期刊

第一作者： Hao, Ya

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

作者机构：

期刊名称：SCIENTIFIC REPORTS （ 影响因子：4.379； 五年影响因子：5.133 ）

ISSN： 2045-2322

年卷期： 2017 年 7 卷

页码：

收录情况： SCI

摘要： Bovine lactoferricin (LfcinB) has potent antibacterial, antifungal and antiparasitic activities but is also hemolytic. Our objective was to identify LfcinB17-31 derivatives with reduced hemolysis and improved antimicrobial activity via substituting Cys3, Arg4, Gln7, Met10, and Gly14 with more hydrophobic residues. Two peptides, Lfcin4 and Lfcin5, showed higher activity against Staphylococcus aureus and Salmonella enteritidis and lower hemolytic activity than the parent peptide LfcinB17-31. These peptides permeabilized the outer and inner membranes of S. enteritidis; however, Lfcin5 did not permeabilize the inner membrane of S. aureus. Gel retardation and circular dichroism spectra showed that Lfcin4 and Lfcin5 bound to bacterial genomic DNA. Lfcin4 inhibited DNA, RNA and protein synthesis. Both peptides induced the peeling of membranes and the lysis of S. enteritidis. At doses of 10 and 15 mg/kg, Lfcin4 and Lfcin5 reduced the bacterial counts in infected thigh muscles by 0.03. 0.10 and 0.05. 0.63 log10 CFU/g of tissue, respectively, within 10 h. Lfcin4 and Lfcin5 enhanced the survival rate of endotoxemic mice; reduced serum IL-6, IL-1 beta and TNF-alpha levels; and protected mice from lipopolysaccharide-induced lung injury. These data suggest that Lfcin4 and Lfcin5 may be antimicrobial and anti-endotoxin peptides that could serve as the basis for the development of dual-function agents.

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