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从烟曲霉 nHF-01 中生产和表征广谱抗菌 5-正丁基-2-吡啶甲酸。

Production and characterization of a broad-spectrum antimicrobial 5-butyl-2-pyridine carboxylic acid from Aspergillus fumigatus nHF-01.

机构信息

Plant and Microbial Physiology and Biochemistry Laboratory, Department of Botany, University of Gour Banga, Malda, West Bengal, India.

Department of Chemistry, University of Gour Banga, Malda, West Bengal, India.

出版信息

Sci Rep. 2022 Apr 9;12(1):6006. doi: 10.1038/s41598-022-09925-z.

DOI:10.1038/s41598-022-09925-z
PMID:35397665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8994762/
Abstract

The present study aims at the production optimization, purification, and characterization of a potent broad-spectrum antimicrobial compound (AMC) produced by Aspergillus fumigatus nHF-01 (GenBank Ac. No. MN190286). The culture conditions were optimized for a higher amount of AMC. The AMC was solvent extracted and characterized by UV-Vis, FT-IR, ESI-MS, and H-NMR spectroscopy. The MIC, MBC and mode of action were determined against a set of Gram-positive and Gram-negative human pathogenic bacteria. Its antibiofilm, synergistic and cytotoxic effects were also tested. The putative target site of action was evaluated through in silico molecular docking study. The stain A. fumigatus nHF-01 produced the maximum AMC (5-butyl-2-pyridine carboxylic acid) in 2% MEB (w/v) and 4% YE (w/v) at pH 6.0 and 20 °C temperature with 100 rpm agitation for ten days. It caused complete lethality of the Gram-positive and Gram-negative human pathogenic bacteria at a 129 µg/mL dose by rupture and entire dissolution of cell integrity. It showed moderate antibiofilm activity and had a synergistic activity with streptomycin and additive effects with ciprofloxacin and vancomycin. It targets a respiratory enzyme, Quinol-Fumarate Reductase (1l0v), with the highest binding affinities. It had cytotoxicity against human lung carcinoma A549 cell line and was stable up to 100 °C. Thus, the study revealed that the strain A. fumigatus nHF-01 produces a potent broad-spectrum AMC 5-butyl-2-pyridine carboxylic acid that could be used against human food and topical pathogenic bacteria. This is the first report of such a compound produced from the A. fumigatus.

摘要

本研究旨在优化 Aspergillus fumigatus nHF-01(GenBank Ac. No. MN190286)产生的一种强效广谱抗菌化合物(AMC)的生产、纯化和特性。优化了培养条件以获得更多的 AMC。采用溶剂萃取法提取 AMC,并通过 UV-Vis、FT-IR、ESI-MS 和 H-NMR 光谱对其进行了表征。测定了一系列革兰氏阳性和革兰氏阴性人类致病菌对 AMC 的 MIC、MBC 和作用方式。还测试了其抗生物膜、协同和细胞毒性作用。通过计算机分子对接研究评估了潜在的作用靶位。在 2% MEB(w/v)和 4% YE(w/v)、pH 6.0 和 20°C 温度下,以 100rpm 搅拌 10 天,A. fumigatus nHF-01 产生的 AMC(5-丁基-2-吡啶甲酸)最多。在 129µg/mL 剂量下,它通过破坏和完全溶解细胞完整性,导致革兰氏阳性和革兰氏阴性人类致病菌完全致死。它表现出适度的抗生物膜活性,与链霉素具有协同作用,与环丙沙星和万古霉素具有相加作用。它以 Quinol-Fumarate Reductase(1l0v)为靶标,具有最高的结合亲和力。它对人肺癌 A549 细胞系具有细胞毒性,在 100°C 下仍保持稳定。因此,该研究表明,A. fumigatus nHF-01 产生一种强效广谱 AMC 5-丁基-2-吡啶甲酸,可用于对抗人类食品和局部致病菌。这是首次从 A. fumigatus 中报道此类化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/1ddadef906e1/41598_2022_9925_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/7b2b7c586d77/41598_2022_9925_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/4da084c5dbc2/41598_2022_9925_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/1ddadef906e1/41598_2022_9925_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/7b2b7c586d77/41598_2022_9925_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/8d9ba872ac9c/41598_2022_9925_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/77e6ad774022/41598_2022_9925_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/c1f6527fc4f4/41598_2022_9925_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/4da084c5dbc2/41598_2022_9925_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41a5/8994762/1ddadef906e1/41598_2022_9925_Fig6_HTML.jpg

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