Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: Potent activity against oral pathogens
Antimicrobial and immunomodulatory properties of PGLa-AM1, CPF-AM1, and magainin-AM1: Potent activity against oral pathogens
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DOI：
10.1016/j.regpep.2014.11.002
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发表时间：
2014-11-01
影响因子：
--
通讯作者：
Lundy, Fionnuala T.
中科院分区：
文献类型：
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作者：
McLean, Denise T. F.;McCrudden, Maeliosa T. C.;Lundy, Fionnuala T.
阳离子两亲性α-螺旋肽是一类被广泛研究的宿主防御肽。研究了从去甲肾上腺素刺激的非洲火山蛙非洲爪蟾皮肤分泌物中分离的三种肽，肽甘氨酸-亮氨酸-酰胺（PGLa-AM 1），雨蛙素-前体片段（CPF-AM 1）和magainin-AM 1对口腔和呼吸道病原体的抗菌和免疫调节活性。最低有效浓度（MEC），由径向扩散测定，一般低于最低抑菌浓度（MIC）确定的微量肉汤稀释。PGLa-AM 1和CPF-AM 1对变形链球菌特别有效，所有三种肽对具核梭杆菌有效，而粪肠球菌和白色念珠菌被证明是相对耐药的微生物。铜绿假单胞菌的模式菌株被证明比研究的临床分离株更敏感。PGLa-AM 1显示出与来自大肠杆菌、铜绿假单胞菌和牙龈卟啉单胞菌的脂多糖（LPS）结合的最大倾向。所有三种肽显示与牙龈卟啉单胞菌LPS的结合比与来自所研究的其他物种的LPS的结合少。口服成纤维细胞活力不受50 μ M肽处理的影响。用1或10 μ M爪蟾抗菌素-AM 1处理后，口腔成纤维细胞产生的促炎细胞因子IL-8显著增加，但用PGla-AM 1或CPF-AM 1处理后没有增加。总之，X. Amieti肽与来自三种人类病原体的LPS结合，对口腔成纤维细胞活力没有影响。CPF-AM 1和PGLa-AM 1显示出作为用于设计用于治疗与细菌或真菌相关的口腔和牙科疾病的新型类似物的模板的前景。(C)2014爱思唯尔有限公司版权所有。
Cationic amphipathic a-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 albi cans 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 mu M peptide treatments. Production of the pro-inflammatory cytokine IL-8 by oral fibroblasts was significantly increased following treatment with I or 10 mu M 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. (C) 2014 Elsevier B.V. All rights reserved.