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虾青素1对白色念珠菌的抗真菌活性及成孔机制

Antifungal activity and pore-forming mechanism of astacidin 1 against Candida albicans.

作者信息

Choi Hyemin, Lee Dong Gun

机构信息

School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea.

School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea.

出版信息

Biochimie. 2014 Oct;105:58-63. doi: 10.1016/j.biochi.2014.06.014. Epub 2014 Jun 21.

DOI:10.1016/j.biochi.2014.06.014
PMID:24955933
Abstract

In a previous report, a novel antibacterial peptide astacidin 1 (FKVQNQHGQVVKIFHH) was isolated from hemocyanin of the freshwater crayfish Pacifastacus leniusculus. In this study, the antifungal activity and mechanism of astacidin 1 were evaluated. Astacidin 1 exhibited antifungal activity against Candida albicans, Trichosporon beigelii, Malassezia furfur, and Trichophyton rubrum. Also, astacidin 1 had fungal cell selectivity in human erythrocytes without causing hemolysis. To understand the antifungal mechanism, membrane studies were done against C. albicans and T. beigelii. Flow cytometric analysis and K(+) measurement showed membrane damage, resulting in membrane permeabilization and K(+) release-induced membrane depolarization. Furthermore, the calcein leakage from liposomes mimicking C. albicans membrane demonstrated that the membrane-active action was driven by pore-forming mechanism. Live cell imaging using fluorescein isothiocyanate-labeled dextrans of various sizes suggested that the radii of pores formed in the C. albicans membrane were 1.4-2.3 nm. Therefore, the present study suggests that astacidin 1 exerts its antifungal effect by damaging the fungal membrane via pore formation.

摘要

在之前的一份报告中,从淡水小龙虾美洲螯龙虾的血蓝蛋白中分离出一种新型抗菌肽虾红素1(FKVQNQHGQVVKIFHH)。在本研究中,对虾红素1的抗真菌活性及其作用机制进行了评估。虾红素1对白色念珠菌、白吉利丝孢酵母、糠秕马拉色菌和红色毛癣菌均表现出抗真菌活性。此外,虾红素1在人红细胞中具有真菌细胞选择性,不会引起溶血。为了解其抗真菌机制,针对白色念珠菌和白吉利丝孢酵母进行了膜研究。流式细胞术分析和钾离子测量显示膜损伤,导致膜通透性增加和钾离子释放诱导的膜去极化。此外,模拟白色念珠菌膜的脂质体中钙黄绿素泄漏表明,膜活性作用是由成孔机制驱动的。使用异硫氰酸荧光素标记的不同大小葡聚糖进行的活细胞成像表明,白色念珠菌膜中形成的孔半径为1.4 - 2.3纳米。因此,本研究表明虾红素1通过成孔作用破坏真菌膜发挥其抗真菌作用。

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