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硒介导的保护作用可逆转细菌对杀菌抗生素的敏感性。

Selenium-mediated protection in reversing the sensitivity of bacterium to the bactericidal antibiotics.

作者信息

Li Zhonglei, Tan Jun, Shao Lei, Dong Xiaojing, Ye Richard D, Chen Daijie

机构信息

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; China State Institute of Pharmaceutical Industry, Shanghai Institute of Pharmaceutical Industry, Shanghai 201203, China.

China State Institute of Pharmaceutical Industry, Shanghai Institute of Pharmaceutical Industry, Shanghai 201203, China.

出版信息

J Trace Elem Med Biol. 2017 May;41:23-31. doi: 10.1016/j.jtemb.2017.02.007. Epub 2017 Feb 12.

Abstract

Inducing production of damaging reactive oxygen species (ROS) is an important criterion to distinguish the bactericidal antibiotics from bacteriostatic antibiotics. Selenoenzymes were generally recognized to be a powerful antioxidant capable of scavenging free radicals, protecting the cells from the harmful effects of ROS. Therefore, the present study was carried out to investigate the selenium (Se)-mediated protection in reversing antibiotic sensitivity and the role of selenoenzymes in alleviating the negative effects of oxidative stress. The cellular antioxidant activity of Se-enriched bacteria was analyzed, as well as intracellular ROS production and elimination when Se-enriched bacteria in the presence of various antibiotics. Compared to complete inhibition of the parental strain by bactericidal antibiotics, it only exhibited slight and reversible inhibition of Se-enriched Escherichia coli ATCC25922 and Staphylococcus aureus ATCC25923 at the same conditions, which indicated that intracellular selenium provided substantial protection against antibiotics. ROS generation caused by bactericidal antibiotics was confirmed by fluorescence spectrophotometry using 2', 7'-dichloro- uorescein diacetate (DCFH-DA) as substrate. The time course experiments of pretreatment with selenium showed significant decrease of ROS level at 2h. In summary, the present study provides experimental evidence supporting selenoenzymes has good scavenging effect to ROS and can protect bacteria from oxidative stress injury induced by bactericidal antibiotics.

摘要

诱导产生具有破坏性的活性氧(ROS)是区分杀菌性抗生素和抑菌性抗生素的重要标准。硒酶通常被认为是一种强大的抗氧化剂,能够清除自由基,保护细胞免受ROS的有害影响。因此,本研究旨在探讨硒(Se)介导的保护作用在逆转抗生素敏感性方面的作用以及硒酶在减轻氧化应激负面影响中的作用。分析了富硒细菌的细胞抗氧化活性,以及在各种抗生素存在下富硒细菌的细胞内ROS产生和消除情况。与杀菌性抗生素对亲本菌株的完全抑制相比,在相同条件下,它仅对富硒大肠杆菌ATCC25922和金黄色葡萄球菌ATCC25923表现出轻微且可逆的抑制,这表明细胞内的硒提供了对抗生素的实质性保护。以2',7'-二氯荧光素二乙酸酯(DCFH-DA)为底物,通过荧光分光光度法证实了杀菌性抗生素引起的ROS生成。硒预处理的时间进程实验表明,在2小时时ROS水平显著降低。总之,本研究提供了实验证据,支持硒酶对ROS具有良好的清除作用,并能保护细菌免受杀菌性抗生素诱导的氧化应激损伤。

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