Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides.
Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides.
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DOI：
10.2147/idr.s166236
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发表时间：
2018
影响因子：
3.9
通讯作者：
Alzoubi KH
中科院分区：
文献类型：
--
作者：
Almaaytah A;Qaoud MT;Abualhaijaa A;Al-Balas Q;Alzoubi KH
随着新型抗菌药物的发展面临历史性的衰退，细菌耐药性问题已成为威胁全球人口的严重困境。抗菌肽(AMPs)是一类极具吸引力和发展前景的抗菌剂。AMP的杂交旨在合并两个单独的天然多肽活性片段，以产生具有改变的物理化学性质的新AMP，从而转化为增强的安全性。在本研究中，我们通过将BMAP-27和OP-145的两个单独的α-螺旋片段结合在一起，合理地设计了一个新的杂交肽。对生成的多肽进行了抗菌活性和对一系列微生物菌株的抗生物膜活性的评价。用溶血法和抗增殖试验评价了合成的多肽对哺乳动物细胞的毒性。H4的抗菌活性表明，该多肽对革兰氏阳性菌和革兰氏阴性菌都显示出广泛的活性，包括标准和多重耐药细菌菌株，范围在2.5-25μM。新的杂交肽对生物被膜形成细胞显示出强大的活性，报告的最低生物被膜消除浓度等于已报道的浮游细胞的最低抑制浓度。此外，H4对真核细胞的毒性降低。将H4多肽与常规抗生素相结合，以协同或相加的方式显著提高了两种抗菌剂的抗菌活性。总体而言，这项研究表明，杂交和协同策略在开发AMPs作为潜在的抗菌治疗药物方面是成功的，这种药物的毒性特征降低，可以有效地用于根除耐药细菌菌株，并提高天然AMPs的选择性和毒性特征。
As the development of new antimicrobial agents faces a historical decline, the issue of bacterial drug resistance has become a serious dilemma that threatens the human population worldwide. Antimicrobial peptides (AMPs) represent an attractive and a promising class of antimicrobial agents. The hybridization of AMPs aimed at merging two individual active fragments of native peptides to generate a new AMP with altered physicochemical properties that translate into an enhanced safety profile. In this study, we have rationally designed a new hybrid peptide via combining two individual α-helical fragments of both BMAP-27 and OP-145. The resultant peptide, was evaluated for its antimicrobial and antibiofilm activity against a range of microbial strains. The resultant peptide was also evaluated for its toxicity against mammalian cells using hemolytic and anti proliferative assays. The antimicrobial activity of H4 revealed that the peptide is displaying a broad spectrum of activity against both Gram-positive and Gram-negative bacteria including standard and multidrug-resistant bacterial strains in the range of 2.5–25 μM. The new hybrid peptide displayed potent activity in eradicating biofilm-forming cells, and the reported minimum biofilm eradication concentrations were equal to the minimum inhibitory concentration values reported for planktonic cells. Additionally, H4 exhibited reduced toxicity profiles against eukaryotic cells. Combining H4 peptide with conventional antibiotics has led to a dramatic enhancement of the antimicrobial activity of both agents with synergistic or additive outcomes. Overall, this study indicates the success of both the hybridization and synergism strategy in developing AMPs as potential antimicrobial therapeutics with reduced toxicity profiles that could be efficiently employed to eradicate resistant bacterial strains and enhance the selectivity and toxicity profiles of native AMPs.