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从印度东北部森林土壤中分离出的链霉菌 NP73 对多药耐药大肠杆菌的抗菌潜力。

Antimicrobial potential of Streptomyces sp. NP73 isolated from the forest soil of Northeast India against multi-drug resistant Escherichia coli.

机构信息

Microbial Biotechnology Laboratory, Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, Assam 781035, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

出版信息

Lett Appl Microbiol. 2024 Sep 2;77(9). doi: 10.1093/lambio/ovae086.

Abstract

This study reports the isolation and characterization of a Streptomyces sp. from soil, capable of producing bioactive secondary metabolites active against a variety of bacterial human pathogens. We targeted the antimicrobial activity against Escherichia coli ATCC-BAA 2469, a clinically relevant strain of bacteria harbouring resistance genes for carbapenems, extended spectrum beta-lactams, tetracyclines, fluoroquinones, etc. Preliminary screening using the spot inoculation technique identified Streptomyces sp. NP73 as the potent strain among the 74 isolated Actinomycetia strain. 16S rRNA gene and whole genome sequencing (WGS) confirmed its taxonomical identity and helped in the construction of the phylogenetic tree. WGS revealed the predicted pathways and biosynthetic gene clusters responsible for producing various types of antibiotics including the isolated compound. Bioactivity guided fractionation and chemical characterization of the active fraction, carried out using liquid chromatography, gas chromatography-mass spectrometry, infra-red spectroscopy, and nuclear magnetic resonance spectroscopy, led to the tentative identification of the active compound as Pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-, a diketopiperazine molecule. This compound exhibited excellent antimicrobial and anti-biofilm properties against E. coli ATCC-BAA 2469 with an MIC value of 15.64 µg ml-1, and the low cytotoxicity of the compound identified in this study provides hope for future drug development.

摘要

本研究报告了一种从土壤中分离出来的链霉菌(Streptomyces sp.),该菌株能够产生针对多种人类病原菌的活性生物次生代谢物。我们针对的是对大肠杆菌 ATCC-BAA 2469 的抗菌活性,大肠杆菌 ATCC-BAA 2469 是一种具有碳青霉烯类、扩展谱β-内酰胺类、四环素类、氟喹诺酮类等耐药基因的临床相关细菌菌株。采用点接种技术进行初步筛选,从 74 株分离出的放线菌菌株中确定了链霉菌 NP73 为有效菌株。16S rRNA 基因和全基因组测序(WGS)确认了其分类学身份,并有助于构建系统发育树。WGS 揭示了负责产生各种类型抗生素的预测途径和生物合成基因簇,包括分离出的化合物。采用液相色谱、气相色谱-质谱联用、红外光谱和核磁共振波谱对活性部分进行生物活性导向分离和化学表征,初步鉴定出活性化合物为吡咯并[1,2-a]吡嗪-1,4-二酮,六氢-,一种二酮哌嗪分子。该化合物对大肠杆菌 ATCC-BAA 2469 表现出优异的抗菌和抗生物膜特性,MIC 值为 15.64 µg ml-1,且该研究中鉴定出的化合物的低细胞毒性为未来药物开发提供了希望。

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