PGLa-AM1, CPF-AM1和magainin-AM1的抗菌和免疫调节特性:对口腔病原体的有效活性

Denise T.F. McLean , Maelíosa T.C. McCrudden , Gerard J. Linden , Christopher R. Irwin , J. Michael Conlon , Fionnuala T. Lundy
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引用次数: 20

摘要

阳离子两性α-螺旋肽是一类被广泛研究的宿主防御肽(hdp)。从非洲火山蛙去甲肾上腺素刺激下的皮肤分泌物中分离出甘氨酸-亮氨酸-酰胺肽(PGLa-AM1)、毛蛋白前体片段(CPF-AM1)和magainin-AM1,研究了它们对口腔和呼吸道病原体的抗菌和免疫调节活性。径向扩散法测定的最低有效浓度(MECs)通常低于微肉汤稀释法测定的最低抑制浓度(mic)。PGLa-AM1和CPF-AM1对变形链球菌特别有效,这三种肽对核梭杆菌都有效,而粪肠球菌和白色念珠菌被证明是相对耐药的微生物。一种类型的铜绿假单胞菌被证明比临床分离研究更敏感。PGLa-AM1对大肠杆菌、铜绿假单胞菌和牙龈卟啉单胞菌的脂多糖(LPS)结合能力最强。这三种肽与牙龈卟啉卟啉脂多糖的结合程度均低于与其他物种的结合程度。50 μM肽处理对口腔成纤维细胞活力无影响。1 μM magainin-AM1或10 μM magainin-AM1治疗后,口腔成纤维细胞产生的促炎细胞因子IL-8显著增加,而PGLa-AM1或CPF-AM1治疗后则没有。综上所述,除了具有有效的抗菌作用外,X. amieti肽与三种人类病原体的LPS结合,对口腔成纤维细胞的活力没有影响。CPF-AM1和PGLa-AM1有望成为设计新型类似物的模板,用于治疗与细菌或真菌相关的口腔和牙齿疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: Potent activity against oral pathogens

Cationic amphipathic α-helical peptides are intensively studied classes of host defence peptides (HDPs). Three peptides, peptide glycine–leucine–amide (PGLa-AM1), caerulein-precursor fragment (CPF-AM1) and magainin-AM1, originally isolated from norepinephrine-stimulated skin secretions of the African volcano frog Xenopus amieti (Pipidae), were studied for their antimicrobial and immunomodulatory activities against oral and respiratory pathogens. Minimal effective concentrations (MECs), determined by radial diffusion assay, were generally lower than minimal inhibitory concentrations (MICs) determined by microbroth dilution. PGLa-AM1 and CPF-AM1 were particularly active against Streptococcus mutans and all three peptides were effective against Fusobacterium nucleatum, whereas Enterococcus faecalis and Candida albicans proved to be relatively resistant micro-organisms. A type strain of Pseudomonas aeruginosa was shown to be more susceptible than the clinical isolate studied. PGLa-AM1 displayed the greatest propensity to bind lipopolysaccharide (LPS) from Escherichia coli, P. aeruginosa and Porphyromonas gingivalis. All three peptides showed less binding to P. gingivalis LPS than to LPS from the other species studied. Oral fibroblast viability was unaffected by 50 μM peptide treatments. Production of the pro-inflammatory cytokine IL-8 by oral fibroblasts was significantly increased following treatment with 1 or 10 μM magainin-AM1 but not following treatment with PGLa-AM1 or CPF-AM1. In conclusion, as well as possessing potent antimicrobial actions, the X. amieti peptides bound to LPS from three human pathogens and had no effect on oral fibroblast viability. CPF-AM1 and PGLa-AM1 show promise as templates for the design of novel analogues for the treatment of oral and dental diseases associated with bacteria or fungi.

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来源期刊
Regulatory Peptides
Regulatory Peptides 医学-内分泌学与代谢
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审稿时长
2 months
期刊介绍: Regulatory Peptides provides a medium for the rapid publication of interdisciplinary studies on the physiology and pathology of peptides of the gut, endocrine and nervous systems which regulate cell or tissue function. Articles emphasizing these objectives may be based on either fundamental or clinical observations obtained through the disciplines of morphology, cytochemistry, biochemistry, physiology, pathology, pharmacology or psychology.
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