High throughput screening methods for assessing antibiofilm and immunomodulatory activities of synthetic peptides.
High throughput screening methods for assessing antibiofilm and immunomodulatory activities of synthetic peptides.
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DOI：
10.1016/j.peptides.2015.03.015
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发表时间：
2015-09
期刊：
影响因子：
3
通讯作者：
Hancock RE
中科院分区：
文献类型：
--
作者：
Haney EF;Mansour SC;Hilchie AL;de la Fuente-Núñez C;Hancock RE
最近观察到某些阳离子肽具有有效的抗生物膜活性，表明小肽可用于治疗生物膜相关感染。其他所谓的先天防御调节肽具有强大的免疫调节特性，如白细胞募集和有害炎症的抑制。一种直接针对生物膜细胞的肽，同时有利地调节免疫反应，对于治疗由金黄色葡萄球菌引起的严重皮肤感染特别有利。在目前的工作中，我们利用纤维素膜上的点合成肽阵列，概述了一种系统评估数百种IDR-1002 （vqrwlivwrik - nh2）和IDR-HH2 （VQLRIRVAVIRA-NH2）肽变体对MRSA生物膜的抗生物膜活性的策略。此外，研究人员还评估了这些肽刺激单核细胞趋化蛋白（MCP-1）产生和抑制lps诱导的人外周血单核细胞（PBMCs）白细胞介素(IL)-1β产生的能力。这些结果为第二代肽的合成提供了信息，从而产生了新的肽IDR-2009 (KWRLLIRWRIQK-NH2)，该肽具有增强的MCP-1刺激活性，良好的IL-1β抑制特性以及对MRSA和铜绿假单胞菌生物膜的强抗生物膜活性。这项工作提供了一个概念证明，多个肽活性可以同时优化，以产生具有多种生物学特性的新序列。
The recent observation that certain cationic peptides possess potent antibiofilm activity demonstrated that small peptides could be used to treat biofilm-associated infections. Other so-called innate defense regulator peptides possess potent immunomodulatory properties such as leukocyte recruitment and suppression of harmful inflammation. A peptide that directly targets biofilm cells while favourably modulating the immune response would be particularly advantageous for treating serious skin infections caused by S. aureus. In the present work, using SPOT-synthesized peptide arrays on cellulose membranes, we outline a strategy for systematically assessing the antibiofilm activity of hundreds of IDR-1002 (VQRWLIVWRIRK-NH2) and IDR-HH2 (VQLRIRVAVIRA-NH2) peptide variants against MRSA biofilms. In addition, the ability of these peptides to stimulate production of a monocyte chemoattractant protein (MCP-1) and suppress LPS-induced interleukin (IL)-1β production in human peripheral blood mononuclear cells (PBMCs) was evaluated. These results informed the synthesis of second-generation peptides resulting in a new peptide, IDR-2009 (KWRLLIRWRIQK-NH2), with enhanced MCP-1 stimulatory activity, favourable IL-1β suppression characteristics and strong antibiofilm activity against MRSA and Pseudomonas aeruginosa biofilms. This work provides a proof-of-concept that multiple peptide activities can be optimized simultaneously to generate novel sequences that possess a variety of biological properties.