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揭示新型毕赤酵母生物表面活性剂的潜力:触发氧化应激以实现有前景的抗真菌和抗癌活性。

Unveiling the potential of novel Metschnikowia yeast biosurfactants: triggering oxidative stress for promising antifungal and anticancer activity.

机构信息

Institute of Microbial Technology, CSIR, Sector 39-A, Chandigarh, 160036, India.

出版信息

Microb Cell Fact. 2024 Sep 11;23(1):245. doi: 10.1186/s12934-024-02489-9.

DOI:10.1186/s12934-024-02489-9
PMID:39261862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11389333/
Abstract

BACKGROUND

Sophorolipids are glycolipid biosurfactants with potential antibacterial, antifungal, and anticancer applications, rendering them promising for research. Therefore, this study hypothesizes that sophorolipids may have a notable impact on disrupting membrane integrity and triggering the production of reactive oxygen species, ultimately resulting in the eradication of pathogenic microbes.

RESULTS

The current study resulted in the isolation of two Metschnikowia novel yeast strains. Sophorolipids production from these strains reached maximum yields of 23.24 g/l and 21.75 g/l, respectively, at the bioreactors level. Biosurfactants sophorolipids were characterized using FTIR and LC-MS techniques and found to be a mixture of acidic and lactonic forms with molecular weights of m/z 678 and 700. Our research elucidated sophorolipids' mechanism in disrupting bacterial and fungal membranes through ROS generation, confirmed by transmission electron microscopy and FACS analysis. The results showed that these compounds disrupted the membrane integrity and induced ROS production, leading to cell death in Klebsiella pneumoniae and Fusarium solani. In addition, the anticancer properties of sophorolipids were investigated on the A549 lung cancer cell line and found that sophorolipid-11D (SL-11D) and sophorolipid-11X (SL-11X) disrupted the actin cytoskeleton, as evidenced by immunofluorescence microscopy. The A549 cells were stained with Acridine orange/Ethidium bromide, which showed that they underwent necrosis. This was confirmed by flow cytometric analysis using Annexin/PI staining. The SL-11D and SL-11X molecules exhibited low levels of haemolytic activity and in-vitro cytotoxicity in HEK293, Caco-2, and L929 cell lines.

CONCLUSION

In this work, novel yeast species CIG-11D and CIG-11X, isolated from the bee's gut, produce significant yields of sophorolipids without needing secondary oil sources, indicating a more economical production method. Our research shows that sophorolipids disrupt bacterial and fungal membranes via ROS production. They suggest they may act as chemo-preventive agents by inducing apoptosis in lung cancer cells, offering the potential for enhancing anticancer therapies.

摘要

背景

槐糖脂是一种具有潜在抗菌、抗真菌和抗癌应用的糖脂生物表面活性剂,具有广阔的研究前景。因此,本研究假设槐糖脂可能对破坏细胞膜完整性和触发活性氧产生有显著影响,最终导致病原微生物的根除。

结果

本研究从蜜蜂肠道中分离出两种新型酵母菌株 CIG-11D 和 CIG-11X,在生物反应器水平下,槐糖脂的产量分别达到了 23.24 g/L 和 21.75 g/L。采用傅里叶变换红外光谱(FTIR)和液相色谱-质谱联用(LC-MS)技术对槐糖脂生物表面活性剂进行了表征,结果表明其为酸性和内酯形式的混合物,分子量为 m/z 678 和 700。我们的研究通过 ROS 生成阐明了槐糖脂破坏细菌和真菌细胞膜的机制,这一结果通过透射电子显微镜和流式细胞术分析得到了证实。结果表明,这些化合物破坏了细胞膜的完整性并诱导了 ROS 的产生,导致肺炎克雷伯菌和尖孢镰刀菌的死亡。此外,还研究了槐糖脂对 A549 肺癌细胞系的抗癌特性,发现槐糖脂-11D(SL-11D)和槐糖脂-11X(SL-11X)破坏了肌动蛋白细胞骨架,这一点通过免疫荧光显微镜得到了证实。用吖啶橙/溴化乙锭对 A549 细胞进行染色,结果表明它们发生了坏死。这一结果通过 Annexin/PI 染色的流式细胞术分析得到了证实。SL-11D 和 SL-11X 分子在 HEK293、Caco-2 和 L929 细胞系中表现出较低的溶血活性和体外细胞毒性。

结论

在这项工作中,从蜜蜂肠道中分离出的新型酵母菌株 CIG-11D 和 CIG-11X 无需使用二次油源即可产生大量的槐糖脂,表明其生产方法更为经济。我们的研究表明,槐糖脂通过 ROS 产生破坏细菌和真菌的细胞膜。它们表明,槐糖脂可能通过诱导肺癌细胞凋亡发挥化学预防作用,从而为增强抗癌疗法提供了潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/a5f1049080f2/12934_2024_2489_Fig6a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/79dea1e16093/12934_2024_2489_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/8c055669ea35/12934_2024_2489_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/9005b820c6bb/12934_2024_2489_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/942934992b71/12934_2024_2489_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/1c2a5c9ba28a/12934_2024_2489_Fig5a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/a5f1049080f2/12934_2024_2489_Fig6a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/79dea1e16093/12934_2024_2489_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/8c055669ea35/12934_2024_2489_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/9005b820c6bb/12934_2024_2489_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/942934992b71/12934_2024_2489_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/1c2a5c9ba28a/12934_2024_2489_Fig5a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/035b/11389333/a5f1049080f2/12934_2024_2489_Fig6a_HTML.jpg

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