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来自链霉菌属JRG-04的苯并异色满醌聚酮化合物的抗菌特性体外评估及淋巴细胞毒性测定

In-vitro assessment of antimicrobial properties and lymphocytotoxicity assay of benzoisochromanequinones polyketide from Streptomyces sp JRG-04.

作者信息

Govindarajan Ganesan, Kamaraj Raju, Balakrishnan Karuppiah, Santhi Velayudhan Satheeja, Jebakumar Solomon Robinson David

机构信息

Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai, 625021, India.

Department of Immunology, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India.

出版信息

Microb Pathog. 2017 Sep;110:117-127. doi: 10.1016/j.micpath.2017.06.034. Epub 2017 Jun 23.

Abstract

The chromanequinone (BIQ) compound produced by the mangrove estuary derived strain, Streptomyces sp. JRG-04 was effective even at low MIC level concentration against Methicillin resistant S. aureus and other clinical pathogens. In this study, we have investigated the antimicrobial potential of chromanequinone compound by using various microscopy and imaging techniques. The flow cytometry (FACS) analysis suggested the BIQ aromatic polyketide compound produced by the Streptomyces sp. JRG-04 has toxic effect on MRSA cell membrane by increased up take of propidium iodide dye. The bacterial imaging analysis by high content screening experiment (HCS) revealed the increased number of dead MRSA cells than the live MRSA populations with chromanequinone treatment. Furthermore, atomic force microscopic study proved the MRSA cell surface ultra-structure changes when the cells exposed to chromanequinone compound at 3 h and 6 h. Further, in-vitro lymphocytotoxicity effect of chromanequinone compound at different concentrations with the combination of complement was performed on human lymphocytes by cell lysis assay. Interestingly, we have found that the higher concentration of BIQ chromanequinone (10 mg/mL) compound without complement induced apoptosis of human lymphocytes. The present investigation reveals that the toxic potential of chromanequinone on human lymphocytes might be associated with the complement dependent. This study strongly suggests that the chromanequinone compound produced by the Streptomyces strain with bioactive property can be developed as a therapeutic leads for various pharmaceutical applications.

摘要

由红树林河口来源的链霉菌菌株Streptomyces sp. JRG - 04产生的色满醌(BIQ)化合物,即使在低MIC水平浓度下,对耐甲氧西林金黄色葡萄球菌和其他临床病原体也有效。在本研究中,我们使用各种显微镜和成像技术研究了色满醌化合物的抗菌潜力。流式细胞术(FACS)分析表明,Streptomyces sp. JRG - 04产生的BIQ芳香族聚酮化合物通过增加碘化丙啶染料的摄取对耐甲氧西林金黄色葡萄球菌细胞膜有毒性作用。通过高内涵筛选实验(HCS)进行的细菌成像分析显示,用色满醌处理后,死亡的耐甲氧西林金黄色葡萄球菌细胞数量比存活的耐甲氧西林金黄色葡萄球菌群体增加。此外,原子力显微镜研究证明,当细胞在3小时和6小时暴露于色满醌化合物时,耐甲氧西林金黄色葡萄球菌细胞表面超微结构发生变化。此外,通过细胞裂解试验对人淋巴细胞进行了不同浓度的色满醌化合物与补体联合的体外淋巴细胞毒性作用研究。有趣的是,我们发现较高浓度的BIQ色满醌(10 mg/mL)化合物在无补体的情况下可诱导人淋巴细胞凋亡。本研究表明,色满醌对人淋巴细胞的毒性潜力可能与补体依赖性有关。这项研究强烈表明,具有生物活性的链霉菌菌株产生的色满醌化合物可开发为各种药物应用的治疗先导物。

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