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棘肤素 S1 可降低白念珠菌的生长、生物膜形成以及菌丝壁蛋白 1 和天冬氨酸蛋白酶基因的表达。

Dermaseptin-S1 decreases Candida albicans growth, biofilm formation and the expression of hyphal wall protein 1 and aspartic protease genes.

机构信息

Oral Ecology Research Group, Faculty of Dentistry, Laval University, Quebec, QC, Canada.

Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

出版信息

J Appl Microbiol. 2018 Jul;125(1):72-83. doi: 10.1111/jam.13745. Epub 2018 Mar 25.

Abstract

AIMS

This study aimed to investigate the effect of synthetic antimicrobial peptide dermaseptin-S1 (DS1) (ALWKTMLKKLGTMALHAGKAALGAADTISQGTQ) on the growth of Candida albicans, its transition from blastospore to hyphae, and its biofilm formation. We also analysed the expression of different genes (HWP1 and SAPs) involved in C. albicans virulence.

METHODS AND RESULTS

Using cell count we showed that in addition to decreasing C. albicans growth, peptide DS1 inhibited its transition from blastospore to hyphal form. These effects are comparable to those obtained with amphotericin B (AmB). Electron microscopy analyses showed that C. albicans cells treated with either DS1 or AmB displayed a distorted cell wall surface, suggesting that the effect of DS1 was similar to that of AmB on C. albicans cell membrane structure. These observations were confirmed by our results with biofilms showing that both DS1 peptide and AmB significantly inhibited biofilm formation after 2 and 4 days. The effect of DS1 on C. albicans growth, transition and biofilm formation may occur through gene modulation, as the expression of HWP1, SAP1, SAP2, SAP3, SAP9 and SAP10 genes involved in C. albicans pathogenesis were all downregulated when C. albicans was treated with DS1.

CONCLUSIONS

DS1 inhibits the growth and hyphal transition of C. albicans. DS1 was also able to decrease the expression of and gene expression of hyphal wall protein 1 and aspartic proteases genes by C. albicans.

SIGNIFICANCE AND IMPACT OF THE STUDY

These data provide new insight into the efficacy of DS1 against C. albicans and its potential for use as an antifungal therapy.

摘要

目的

本研究旨在探讨合成抗菌肽 dermaseptin-S1 (DS1) (ALWKTMLKKLGTMALHAGKAALGAADTISQGTQ) 对白色念珠菌生长、从芽生孢子向菌丝过渡以及生物膜形成的影响。我们还分析了与白色念珠菌毒力相关的不同基因 (HWP1 和 SAPs) 的表达。

方法和结果

通过细胞计数,我们发现肽 DS1 除了抑制白色念珠菌生长外,还抑制其从芽生孢子向菌丝形态的转变。这些作用与两性霉素 B (AmB) 的作用相当。电子显微镜分析显示,用 DS1 或 AmB 处理的白色念珠菌细胞显示出细胞壁表面变形,表明 DS1 的作用类似于 AmB 对白色念珠菌细胞膜结构的作用。我们的生物膜实验结果证实了这一点,结果表明 DS1 肽和 AmB 都能显著抑制 2 天和 4 天后生物膜的形成。DS1 对白色念珠菌生长、过渡和生物膜形成的影响可能是通过基因调节实现的,因为当白色念珠菌用 DS1 处理时,与白色念珠菌发病机制相关的 HWP1、SAP1、SAP2、SAP3、SAP9 和 SAP10 基因的表达均下调。

结论

DS1 抑制白色念珠菌的生长和菌丝过渡。DS1 还能够降低白色念珠菌菌丝壁蛋白 1 和天冬氨酸蛋白酶基因的表达和基因表达。

研究的意义和影响

这些数据为 DS1 对白色念珠菌的疗效提供了新的见解,并为其作为抗真菌治疗的潜在用途提供了依据。

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