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The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss

文献类型： 外文期刊

作者： Qu, Pei 1 ; Gao, Wei 1 ; Chen, Huixian 1 ; Li, Dan 1 ; Yang, Na 1 ; Zhu, Jian 1 ; Feng, Xingjun 1 ; Liu, Chunlong 2 ; Li, Zh 1 ;

作者机构： 1.Northeast Agr Univ, Coll Anim Sci & Technol, Harbin, Peoples R China

2.Chinese Acad Sci, Northeast Inst Geog & Agr Ecol, Harbin, Peoples R China

3.Collaborat Innovat Ctr Dev & Utilizat Forest Reso, Harbin, Peoples R China

4.Heilongjiang Acad Agr Sci, Anim Husb Res Ctr, Harbin, Peoples R China

期刊名称：ANTIMICROBIAL AGENTS AND CHEMOTHERAPY （ 影响因子：5.191； 五年影响因子：5.346 ）

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收录情况： SCI

摘要： Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N-nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-2027) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(115-20-27) could be a promising antimicrobial agent for clinical application.

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