Fowlicidin-3 is an α-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities
Fowlicidin-3 is an α-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities
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DOI：
10.1111/j.1742-4658.2006.05589.x
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发表时间：
2007-01-01
期刊：
影响因子：
5.4
通讯作者：
Zhang, Guolong
中科院分区：
文献类型：
--
作者：
Bommineni, Yugendar R.;Dai, Huaien;Zhang, Guolong
Cathelicidins是脊椎动物中一类重要的阳离子宿主防御肽，具有抗菌和免疫调节作用。Fowlicidin-1和Fowlicidin-2是两种新发现的具有较强抗菌活性的鸡Cathelicidin。在这里，我们报告的结构和功能表征的脓成熟形式的第三鸡cathelicidin，fowlicidin-3，探索其治疗潜力。NMR光谱显示，fowlicidin-3包含27个氨基酸残基，并采用从残基9延伸至25的主要α-螺旋结构，在位置17处具有由甘氨酸诱导的轻微扭结。它在体外对广泛的革兰氏阴性和革兰氏阳性细菌具有高度效力，包括耐药菌株，最小抑制浓度在1-2 μ M范围内。它杀死细菌迅速，渗透细胞质膜立即接触他们。与许多其他具有抗微生物活性的宿主防御肽不同，其抗微生物活性会被血清或盐减弱，杀鸡素-3在50%血清或生理浓度的盐存在下保留了杀细菌活性。此外，它能够抑制小鼠巨噬细胞RAW264.7细胞中脂多糖诱导的促炎基因表达，在10 μ M时几乎完全阻断。Fowlicidin-3作为一种新型的抗微生物和防腐剂，特别是针对耐药性病原体，似乎是未来开发的一个很好的候选者。
Cathelicidins are an important family of cationic host defense peptides in vertebrates with both antimicrobial and immunomodulatory activities. Fowlicidin-1 and fowlicidin-2 are two newly identified chicken cathelicidins with potent antibacterial activities. Here we report structural and functional characterization of the putatively mature form of the third chicken cathelicidin, fowlicidin-3, for exploration of its therapeutic potential. NMR spectroscopy revealed that fowlicidin-3 comprises 27 amino-acid residues and adopts a predominantly alpha-helical structure extending from residue 9 to 25 with a slight kink induced by a glycine at position 17. It is highly potent against a broad range of Gram-negative and Gram-positive bacteria in vitro, including antibiotic-resistant strains, with minimum inhibitory concentrations in the range 1-2 mu M. It kills bacteria quickly, permeabilizing cytoplasmic membranes immediately on coming into contact with them. Unlike many other host defense peptides with antimicrobial activities that are diminished by serum or salt, fowlicidin-3 retains bacteria-killing activities in the presence of 50% serum or physiological concentrations of salt. Furthermore, it is capable of suppressing lipopolysaccharide-induced expression of proinflammatory genes in mouse macrophage RAW264.7 cells, with nearly complete blockage at 10 mu M. Fowlicidin-3 appears to be an excellent candidate for future development as a novel antimicrobial and antisepsis agent, particularly against antibiotic-resistant pathogens.