来自内生真菌的2,4-二叔丁基苯酚可减弱多重耐药病原体的生长。

2,4-Di-tert-butylphenol from Endophytic Fungi attenuates the growth of multidrug-resistant pathogens.

作者信息

Sundar Ranjitha Dhevi V, Arunachalam Sathiavelu

机构信息

Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India.

Department of Biotechnology, VIT School of Agricultural Innovations and Advanced Learning, Vellore Institute of Technology, Vellore, India.

出版信息

Front Microbiol. 2025 Jun 10;16:1575021. doi: 10.3389/fmicb.2025.1575021. eCollection 2025.

Abstract

INTRODUCTION

The continuous emergence of drug-resistant pathogenic bacteria highlights the persistent importance of discovering and developing new antibiotics. Endophytic species are an infinite source of several medicinally essential secondary metabolites.

METHODS

The current study focuses on isolating secondary metabolites from the endophytic TPL11 fungus of plant. These fungi were spectrally analyzed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS), and the structures were predicted. The pure compounds were tested for antagonistic susceptibility to multidrug-resistant (MDR) pathogens using disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill kinetics, and cytotoxicity assays.

RESULTS AND DISCUSSION

Bioactivity-guided extraction of ethyl acetate fungal extract purification yielded a lead compound, 2,4-di-tert-butylphenol (DTB), which was interpreted by combining H NMR, C NMR, and mass spectrometry (MS) data. The compound DTB displayed antagonism against human pathogens with diameters ranging from 16 to 26 mm. The highest antagonistic effect was against methicillin-resistant (MRSA) (ATCC 700699) and VRE (ATCC 51299) with 21 ± 0.2 and 22 ± 0.5 mm zones of inhibition, respectively. The compound had MICs of 3.12 and 6.25 μg/mL, and MBCs of 0.78 and 3.12 μg/mL against MRSA (ATCC 700699) and vancomycin-resistant (VRE) (ATCC 51299), respectively. The time-kill kinetics study reveals that DTB displayed a bactericidal effect against pathogens at higher concentrations, indicating a concentration and time-dependent interaction. In a cytotoxicity assay, it is more active against the cell line with a decrease in cell viability of 50.12% at 1,000 μg/mL concentration. The results highlighted that compound DTB from showed significant pharmaceutical potential, indicating its suitability as a lead molecule. The study outcome suggests that the active lead metabolites isolated for the first time from isolated from plant can be an auspicious antibacterial agent for controlling multidrug-resistant pathogens marking a novel discovery in this domain.

摘要

引言

耐药病原菌的不断出现凸显了发现和开发新型抗生素的持续重要性。内生菌是多种医学必需次生代谢产物的无尽来源。

方法

当前研究聚焦于从植物的内生TPL11真菌中分离次生代谢产物。通过核磁共振(NMR)、傅里叶变换红外光谱(FTIR)、气相色谱 - 质谱联用(GC - MS)对这些真菌进行光谱分析,并预测其结构。使用纸片扩散法、最低抑菌浓度(MIC)、最低杀菌浓度(MBC)、时间 - 杀菌动力学和细胞毒性试验,对纯化合物进行耐多药(MDR)病原体的拮抗敏感性测试。

结果与讨论

生物活性导向的乙酸乙酯真菌提取物纯化提取出一种先导化合物,2,4 - 二叔丁基苯酚(DTB),通过结合氢核磁共振(H NMR)、碳核磁共振(C NMR)和质谱(MS)数据对其进行了解析。化合物DTB对人类病原体表现出拮抗作用,抑菌圈直径范围为16至26毫米。对耐甲氧西林金黄色葡萄球菌(MRSA)(ATCC 700699)和耐万古霉素肠球菌(VRE)(ATCC 51299)的拮抗作用最强,抑菌圈直径分别为21±0.2和22±0.5毫米。该化合物对MRSA(ATCC 700699)和VRE(ATCC 51299)的MIC分别为3.12和6.25μg/mL,MBC分别为0.78和3.12μg/mL。时间 - 杀菌动力学研究表明,DTB在较高浓度下对病原体具有杀菌作用,表明存在浓度和时间依赖性相互作用。在细胞毒性试验中,它对细胞系更具活性,在1000μg/mL浓度下细胞活力降低50.12%。结果突出表明来自[具体植物]的化合物DTB具有显著的药用潜力,表明其适合作为先导分子。研究结果表明,首次从[具体植物]中分离出的活性先导代谢产物可能是控制耐多药病原体的一种有前景的抗菌剂,这在该领域标志着一项新发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c506/12185439/2c270e25e988/fmicb-16-1575021-g0001.jpg

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