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酵母衍生的糖脂可破坏白色念珠菌生物膜并抑制细胞黏附相关基因的表达。

Yeast-derived glycolipids disrupt Candida biofilm and inhibit expression of genes in cell adhesion.

作者信息

Watchaputi Kwanrutai, Songdech Pattanan, Jayasekara Channa, Puttarak Panupong, Lamping Erwin, Cannon Richard D, Soontorngun Nitnipa

机构信息

Excellent Research Laboratory for Yeast Innovation, Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi (KMUTT), Bangkok, 10150, Thailand.

Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, 90110, Songkhla, Thailand.

出版信息

Sci Rep. 2025 Jul 1;15(1):20405. doi: 10.1038/s41598-025-08816-3.

DOI:10.1038/s41598-025-08816-3
PMID:40595376
Abstract

Candida albicans is a leading fungal pathogen in humans, responsible for infections that span from mucosal surfaces to severe systemic diseases. This study aimed to investigate potential ability of yeast-derived glycolipids from Meyerozyma guilliermondii as an antifungal against Candida albicans biofilms. Glycolipid extract (64 µg/mL) reduced metabolic activity by 50% in both immature and mature biofilms, while biofilm mass was reduced at higher concentrations of 128 and 256 µg/mL, respectively. Adhesion, a key step in biofilm formation, decreased by over 50% when cells were treated with glycolipids (16 µg/mL). Gene expression analysis indicated that glycolipids downregulated key adhesion-related gene ACE2, confirming their role in disrupting C. albicans adhesion. Importantly, structural changes in C. albicans biofilms, including reduced hyphal production and wrinkled cell surfaces, were observed under SEM. Nocodazole, a cell cycle synchronizer, arrested cells in the G/M phase, enhancing glycolipid's effects on lowing expression of biofilm-related genes. Lipidomics analysis also revealed a compound with same mass as sophorolipid. Furthermore, purification glycolipid fraction revealed two main forms: lactonic and acidic, compared to standards. Acidic fraction showed superior antibiofilm and anti-inflammatory activity with low toxicity. These findings highlight the potential of yeast-derived glycolipids for biopharmaceutical applications, particularly in treating Candida biofilms.

摘要

白色念珠菌是人类主要的真菌病原体,可引发从粘膜表面感染到严重全身性疾病的各类感染。本研究旨在探究季也蒙毕赤酵母来源的酵母糖脂作为抗白色念珠菌生物膜剂的潜在能力。糖脂提取物(64μg/mL)使未成熟和成熟生物膜中的代谢活性均降低了50%,而在128和256μg/mL的较高浓度下生物膜量分别减少。生物膜形成的关键步骤——黏附,在用糖脂(16μg/mL)处理细胞时下降了50%以上。基因表达分析表明,糖脂下调了关键的黏附相关基因ACE2,证实了它们在破坏白色念珠菌黏附中的作用。重要的是,在扫描电子显微镜下观察到白色念珠菌生物膜的结构变化,包括菌丝产生减少和细胞表面起皱。诺考达唑,一种细胞周期同步剂,使细胞停滞在G/M期,增强了糖脂对降低生物膜相关基因表达的作用。脂质组学分析还揭示了一种与槐糖脂质量相同的化合物。此外,与标准品相比,纯化的糖脂组分显示出两种主要形式:内酯型和酸性型。酸性组分表现出优异的抗生物膜和抗炎活性且毒性低。这些发现突出了酵母来源糖脂在生物制药应用中的潜力,特别是在治疗念珠菌生物膜方面。

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