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对从药用植物白蔹中分离出的内生木霉菌对耐甲氧西林金黄色葡萄球菌(MRSA)的抗菌潜力评估及抗MRSA化合物的生物活性导向分离

Evaluation of the potential of endophytic Trichoderma sp. isolated from medicinal plant Ampelopsis japonica against MRSA and bioassay-guided separation of the anti-MRSA compound.

作者信息

Li Jianbin, Xie Siyun, Gao Qing, Deng Zujun

机构信息

School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.

School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, 528458, People's Republic of China.

出版信息

Braz J Microbiol. 2024 Mar;55(1):543-556. doi: 10.1007/s42770-024-01250-z. Epub 2024 Jan 23.

Abstract

Endophytic fungi have been recognized as a valuable source for the production of biologically active compounds with potential applications in various domains. This study aimed to isolate endophytic fungi from Ampelopsis japonica (Thunb.) Makino and assess their anti-MRSA activity. Meanwhile, chromatographic separation techniques were applied to analyze the constituents of endophytic fungal secondary metabolites. The isolate BLR24, which exhibited strong inhibition activity against MRSA, was identified as Trichoderma virens based on morphological characteristics and ITS sequence analyses. The ethyl acetate extract of BLR24 (EA-BLR24) showed good anti-MRSA activity with the MIC and MBC values of 25 μg/mL and 50 μg/mL, separately. The inhibition of biofilm formation was up to 34.67% under MIC concentration treatment. Meanwhile, EA-BLR24 could significantly reduce the expression of biofilm-related genes (icaA, sarA, and agrA) of MRSA. Based on LC-MS/MS analysis, twenty compounds in EA-BLR24 could be annotated using the GNPS platform, mainly diketopiperazines. The anti-MRSA compound (Fr.1.1) was obtained from EA-BLR24 by bioassay-guided fractionation and determined as gliotoxin. The results indicated that endophytic Trichoderma virens BLR24 isolated from the medical plant A. japonica roots could be a promising source of natural anti-MRSA agents. Endophytic fungal secondary metabolites are abundant in biologically active compounds. Endophytic fungi from medicinal plants could be a source yielding bioactive metabolites of pharmaceutical importance.

摘要

内生真菌已被公认为是生产具有多种潜在应用领域生物活性化合物的宝贵来源。本研究旨在从蛇葡萄中分离内生真菌,并评估其抗耐甲氧西林金黄色葡萄球菌(MRSA)活性。同时,应用色谱分离技术分析内生真菌次生代谢产物的成分。基于形态特征和ITS序列分析,对表现出强烈抗MRSA活性的分离株BLR24鉴定为绿色木霉。BLR24的乙酸乙酯提取物(EA-BLR24)显示出良好的抗MRSA活性,其MIC和MBC值分别为25μg/mL和50μg/mL。在MIC浓度处理下对生物膜形成的抑制率高达34.67%。同时,EA-BLR24可显著降低MRSA生物膜相关基因(icaA、sarA和agrA)的表达。基于LC-MS/MS分析,EA-BLR24中的20种化合物可使用GNPS平台进行注释,主要为二酮哌嗪类。通过生物活性导向分离从EA-BLR24中获得抗MRSA化合物(Fr.1.1),并确定为gliotoxin。结果表明,从药用植物蛇葡萄根部分离得到的内生绿色木霉BLR24可能是天然抗MRSA药物的一个有前景的来源。内生真菌次生代谢产物富含生物活性化合物。药用植物中的内生真菌可能是产生具有药学重要性的生物活性代谢产物的来源。

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