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3-羟基香豆素通过抑制细胞黏附、形态发生和毒力基因调控,对白色念珠菌表现出抗生物膜和抗菌丝功效。

3-Hydroxy coumarin demonstrates anti-biofilm and anti-hyphal efficacy against Candida albicans via inhibition of cell-adhesion, morphogenesis, and virulent genes regulation.

机构信息

Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, 630 003, India.

Department of Biological Sciences and Bioengineering, Inha University, Inharo 100, Incheon, 22212, Republic of Korea.

出版信息

Sci Rep. 2023 Jul 19;13(1):11687. doi: 10.1038/s41598-023-37851-1.

DOI:10.1038/s41598-023-37851-1
PMID:37468600
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10356798/
Abstract

Candida albicans, a common fungus of human flora, can become an opportunistic pathogen and causes invasive candidiasis in immunocompromised individuals. Biofilm formation is the prime cause of antibiotic resistance during C. albicans infections and treating biofilm-forming cells is challenging due to their intractable and persistent nature. The study intends to explore the therapeutic potential of naturally produced compounds by competitive marine bacteria residing in marine biofilms against C. albicans biofilm. To this end, 3-hydroxy coumarin (3HC), a compound identified from the cell-free culture supernatant of the marine bacterium Brevundimonas abyssalis, was found to exhibit anti-biofilm and anti-hyphal activity against both reference and clinical isolates of C. albicans. The compound demonstrated significant inhibitory effects on biofilms and impaired the yeast-to-hyphal transition, wrinkle, and filament morphology at the minimal biofilm inhibitory concentration (MBIC) of 250 µg mL. Intriguingly, quantitative PCR analysis of 3HC-treated C. albicans biofilm revealed significant downregulation of virulence genes (hst7, ume6, efg1, cph1, ras1, als1) associated with adhesion and morphogenesis. Moreover, 3HC displayed non-fungicidal and non-toxic characteristics against human erythrocytes and buccal cells. In conclusion, this study showed that marine biofilms are a hidden source of diverse therapeutic drugs, and 3HC could be a potent drug to treat C. albicans infections.

摘要

白色念珠菌是一种常见的人类菌群真菌,它可以成为机会性病原体,并在免疫功能低下的个体中引起侵袭性念珠菌病。生物膜形成是白色念珠菌感染中抗生素耐药性的主要原因,而治疗形成生物膜的细胞由于其顽固和持久的性质具有挑战性。本研究旨在探索居住在海洋生物膜中的海洋细菌自然产生的化合物对白色念珠菌生物膜的治疗潜力。为此,从海洋细菌 Brevundimonas abyssalis 的无细胞培养上清液中鉴定出的 3-羟基香豆素(3HC)被发现对参考和临床分离的白色念珠菌均具有抗生物膜和抗菌丝活性。该化合物在最低生物膜抑制浓度(MBIC)为 250μg/mL 时对生物膜表现出显著的抑制作用,并破坏了酵母到菌丝的转变、褶皱和丝状形态。有趣的是,用 3HC 处理的白色念珠菌生物膜的定量 PCR 分析显示,与粘附和形态发生相关的毒力基因(hst7、ume6、efg1、cph1、ras1、als1)显著下调。此外,3HC 对人红细胞和颊细胞表现出非杀菌和非毒性特征。总之,本研究表明海洋生物膜是多样化治疗药物的隐藏来源,而 3HC 可能是治疗白色念珠菌感染的有效药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/1a526ba6988c/41598_2023_37851_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/2c2d2cdadf46/41598_2023_37851_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/182a38f06442/41598_2023_37851_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/bf2848294d87/41598_2023_37851_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/7b2afd55ffa0/41598_2023_37851_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/ad29a7e3ec54/41598_2023_37851_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/1a526ba6988c/41598_2023_37851_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/2c2d2cdadf46/41598_2023_37851_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/182a38f06442/41598_2023_37851_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/bf2848294d87/41598_2023_37851_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/7b2afd55ffa0/41598_2023_37851_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/ad29a7e3ec54/41598_2023_37851_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d58/10356798/1a526ba6988c/41598_2023_37851_Fig6_HTML.jpg

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