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首页> 外文期刊>Biochimica et biophysica acta. Biomembranes >A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: Design, synthesis, activity against multidrug-resistant bacteria and Candida
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A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: Design, synthesis, activity against multidrug-resistant bacteria and Candida

机译：从牛乳铁蛋白的N末端修饰域衍生的新型抗菌肽：设计，合成，对耐多药细菌和念珠菌的活性

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摘要

Lactoferrin (LF) is believed to contribute to the host's defense against microbial infections. This work focuses on the antibacterial and antifungal activities of a designed peptide, L10 (WFRKQLKW) by modifying the first eight N-terminal residues of bovine LF by selective homologous substitution of amino acids on the basis of hydrophobicity, L10 has shown potent antibacterial and antifungal properties against clinically isolated extended spectrum beta lactamases (ESBL), producing gram-negative bacteria as well as Candida strains with minimal inhibitory concentrations (MIC) ranging from 1 to 8 μg/mL and 6.5 μg/mL, respectively. The peptide was found to be least hemolytic at a concentration of 800 μg/mL. Interaction with lipopolysaccharide (LPS) and lipid A (LA) suggests that the peptide targets the membrane of gram-negative bacteria. The membrane interactive nature of the peptide, both antibacterial and antifungal, was further confirmed by visual observations employing electron microscopy. Further analyses, by means of propidium iodide based flow cytometry, also supported the membrane permeabilization of Candida cells. The peptide was also found to possess anti-inflammatory properties, by virtue of its ability to inhibit cyclooxygenase-2 (COX-2). L10 therefore emerges as a potential therapeutic remedial solution for infections caused by ESBL positive, gram-negative bacteria and multidrug-resistant (MDR) fungal strains, on account of its multifunctional activities. This study may open up new approach to develop and design novel antimicrobials.
机译：乳铁蛋白（LF）被认为有助于宿主抵抗微生物感染。这项工作着眼于设计的肽L10（WFRKQLKW）的抗菌和抗真菌活性，该方法通过在疏水性的基础上通过氨基酸的选择性同源取代来修饰牛LF的前八个N末端残基，L10已显示出强大的抗菌和抗真菌能力具有临床分离的扩展谱β内酰胺酶（ESBL）的特性，可生产革兰氏阴性细菌以及念珠菌菌株，其最小抑菌浓度（MIC）分别为1至8μg/ mL和6.5μg/ mL。发现该肽在800μg/ mL的浓度下至少具有溶血作用。与脂多糖（LPS）和脂质A（LA）的相互作用表明该肽靶向革兰氏阴性细菌的膜。通过使用电子显微镜的目测进一步证实了该肽的膜相互作用性质，即抗菌和抗真菌。借助基于碘化丙啶的流式细胞术进行的进一步分析也支持念珠菌细胞的膜通透性。由于该肽具有抑制环氧合酶2（COX-2）的能力，因此还具有抗炎特性。因此，由于L10具有多功能活性，因此它可以作为由ESBL阳性，革兰氏阴性细菌和多药耐药（MDR）真菌菌株引起的感染的潜在治疗手段。这项研究可能会为开发和设计新型抗菌药物开辟新的途径。

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