Killing of Staphylococcus aureus and Salmonella enteritidis and neutralization of lipopolysaccharide by 17-residue bovine lactoferricins: improved activity of Trp/Ala-containing molecules.
Killing of Staphylococcus aureus and Salmonella enteritidis and neutralization of lipopolysaccharide by 17-residue bovine lactoferricins: improved activity of Trp/Ala-containing molecules.
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17 残基牛乳铁蛋白杀死金黄色葡萄球菌和肠炎沙门氏菌并中和脂多糖：提高含 Trp/Ala 分子的活性
DOI：
10.1038/srep44278
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发表时间：
2017-03-13
影响因子：
4.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Hao Y;Yang N;Wang X;Teng D;Mao R;Wang X;Li Z;Wang J
牛乳铁蛋白 (LfcinB) 具有有效的抗菌、抗真菌和抗寄生虫活性，但也具有溶血性。我们的目标是通过用更多疏水性残基取代 Cys3、Arg4、Gln7、Met10 和 Gly14 来鉴定具有减少溶血和提高抗菌活性的 LfcinB17-31 衍生物。与母肽 LfcinB17-31 相比，Lfcin4 和 Lfcin5 两种肽对金黄色葡萄球菌和肠炎沙门氏菌具有更高的活性，并且具有更低的溶血活性。这些肽可透化肠炎沙门氏菌的外膜和内膜；然而，Lfcin5 不能透化金黄色葡萄球菌的内膜。凝胶延迟和圆二色光谱表明 Lfcin4 和 Lfcin5 与细菌基因组 DNA 结合。 Lfcin4 抑制 DNA、RNA 和蛋白质合成。两种肽均诱导膜剥离和肠炎沙门氏菌裂解。在剂量为 10 和 15 mg/kg 时，Lfcin4 和 Lfcin5 在 10 小时内将受感染大腿肌肉中的细菌计数分别减少了 0.03-0.10 和 0.05-0.63 log10 CFU/g 组织。 Lfcin4和Lfcin5提高内毒素血症小鼠的存活率；降低血清IL-6、IL-1β和TNF-α水平；并保护小鼠免受脂多糖引起的肺损伤。这些数据表明Lfcin4和Lfcin5可能是抗菌和抗内毒素肽，可以作为开发双功能药物的基础。
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-1β and TNF-α 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.