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5-氟尿苷基于毒力降低对[具体对象1]和[具体对象2]的抗真菌活性

Antifungal Activity of 5-Fluorouridine Against and Based on Virulence Reduction.

作者信息

Lenarczyk Ewa, Oleksiak Damian, Janeczko Monika

机构信息

Doctoral School, The John Paul II Catholic University of Lublin, al. Racławickie 14, 20-950 Lublin, Poland.

Department of Molecular Biology, Faculty of Medicine, The John Paul II Catholic University of Lublin, Konstantynów 1i, 20-708 Lublin, Poland.

出版信息

Molecules. 2025 Jun 25;30(13):2735. doi: 10.3390/molecules30132735.

DOI:10.3390/molecules30132735
PMID:40649252
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12250778/
Abstract

This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against species. We evaluated the responses of nine reference species of spp. and one hundred clinical isolates of to 5-FUrd using the broth microdilution method. Additionally, we assessed the effect of 5-FUrd on selected virulence factors, including biofilm formation, cell adhesion, dimorphism, hydrolase secretion, and hemolytic activity, in the two most sensitive species, and . The frequency of spontaneous mutations occurring in these two species under the influence of 5-FUrd was also determined. Finally, we examined the cytotoxic properties of 5-FUrd against human erythrocytes and zebrafish embryos. Our results demonstrated that 5-FUrd exhibits antifungal activity in vitro, inhibits biofilm formation, suppresses hyphal growth, reduces cell surface hydrophobicity, eradicates mature biofilms, and decreases the secretion of extracellular proteinases and hemolytic activity in and cells. The overall mutation frequency under the selective pressure of 5-FUrd ranged from 2 × 10 to 1.2 × 10 per species. Notably, the exposure to 5-FUrd did not induce significant toxic effects on human erythrocytes or zebrafish embryos. This study highlights the potential clinical application of 5-FUrd as an anti- agent.

摘要

本研究旨在探索5-氟尿苷(5-FUrd)作为抗真菌剂针对[具体物种]的潜在新用途。我们使用肉汤微量稀释法评估了9种[物种名称]参考菌株和100株[临床分离菌株所属物种]临床分离株对5-FUrd的反应。此外,我们评估了5-FUrd对两种最敏感的[物种名称]——[物种A]和[物种B]——中选定毒力因子的影响,这些毒力因子包括生物膜形成、细胞黏附、双态性、水解酶分泌和溶血活性。我们还测定了在5-FUrd影响下这两种[物种名称]中自发突变发生的频率。最后,我们检测了5-FUrd对人红细胞和斑马鱼胚胎的细胞毒性特性。我们的结果表明,5-FUrd在体外表现出抗真菌活性,抑制生物膜形成,抑制菌丝生长,降低细胞表面疏水性,根除成熟生物膜,并减少[物种A]和[物种B]细胞中细胞外蛋白酶的分泌和溶血活性。在5-FUrd的选择压力下,每个物种的总体突变频率范围为2×10至1.2×10。值得注意的是,暴露于5-FUrd对人红细胞或斑马鱼胚胎未诱导出显著的毒性作用。本研究突出了5-FUrd作为抗[具体物种]剂的潜在临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/99d1bbab5f52/molecules-30-02735-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/69edd2efeccf/molecules-30-02735-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/1b96c6defb8d/molecules-30-02735-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/40c828dbac76/molecules-30-02735-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/7b8c6459bcee/molecules-30-02735-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/3c1bed614e78/molecules-30-02735-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/5b41251203a1/molecules-30-02735-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/1cc71ae01d18/molecules-30-02735-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/257b775bcf13/molecules-30-02735-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/99d1bbab5f52/molecules-30-02735-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/69edd2efeccf/molecules-30-02735-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/1b96c6defb8d/molecules-30-02735-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/40c828dbac76/molecules-30-02735-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/7b8c6459bcee/molecules-30-02735-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/3c1bed614e78/molecules-30-02735-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/5b41251203a1/molecules-30-02735-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/1cc71ae01d18/molecules-30-02735-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/257b775bcf13/molecules-30-02735-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff83/12250778/99d1bbab5f52/molecules-30-02735-g009.jpg

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本文引用的文献

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New treatment options for critically important WHO fungal priority pathogens.针对世界卫生组织极为重要的真菌重点病原体的新治疗选择。
Clin Microbiol Infect. 2025 Jun;31(6):922-930. doi: 10.1016/j.cmi.2024.03.006. Epub 2024 Mar 9.
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Advancements and challenges in antifungal therapeutic development.
抗真菌治疗药物研发的进展与挑战。
Clin Microbiol Rev. 2024 Mar 14;37(1):e0014223. doi: 10.1128/cmr.00142-23. Epub 2024 Jan 31.
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Biofilm Formation in Medically Important Species.医学重要菌种中的生物膜形成
J Fungi (Basel). 2023 Sep 22;9(10):955. doi: 10.3390/jof9100955.
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Nucleoside analogues: N-glycosylation methodologies, synthesis of antiviral and antitumor drugs and potential against drug-resistant bacteria and Alzheimer's disease.核苷类似物:N-糖基化方法、抗病毒和抗肿瘤药物的合成以及对抗耐药菌和阿尔茨海默病的潜力。
Carbohydr Res. 2023 Oct;532:108889. doi: 10.1016/j.carres.2023.108889. Epub 2023 Jul 17.
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