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含氧单萜对NorA多药转运蛋白的抑制作用。

Inhibition of the NorA multi-drug transporter by oxygenated monoterpenes.

作者信息

Coêlho Mayara Ladeira, Ferreira Josie Haydée Lima, de Siqueira Júnior José Pinto, Kaatz Glenn W, Barreto Humberto Medeiros, de Carvalho Melo Cavalcante Ana Amélia

机构信息

Laboratory of Toxicology Genetic Research, Federal University of Piauí, Teresina, Piauí, Brazil.

Laboratory of Research in Microbiology, Federal University of Piauí, Teresina, PI, Brazil.

出版信息

Microb Pathog. 2016 Oct;99:173-177. doi: 10.1016/j.micpath.2016.08.026. Epub 2016 Aug 24.

DOI:10.1016/j.micpath.2016.08.026
PMID:27565089
Abstract

The aim of this study was to investigate intrinsic antimicrobial activity of three monoterpenes nerol, dimethyl octanol and estragole, against bacteria and yeast strains, as well as, investigate if these compounds are able to inhibit the NorA efflux pump related to fluoroquinolone resistance in Staphylococcus aureus. Minimal inhibitory concentrations (MICs) of the monoterpenes against Staphylococcus aureus, Escherichia coli and Candida albicans strains were determined by micro-dilution assay. MICs of the norfloxacin against a S. aureus strain overexpressing the NorA protein were determined in the absence or in the presence of the monoterpenes at subinhibitory concentrations, aiming to verify the ability of this compounds act as efflux pump inhibitors. The monoterpenes were inactive against S. aureus however the nerol was active against E. coli and C. albicans. The addition of the compounds to growth media at sub-inhibitory concentrations enhanced the activity of norfloxacin against S. aureus SA1199-B. This result shows that bioactives tested, especially the nerol, are able to inhibit NorA efflux pump indicating a potential use as adjuvants of norfloxacin for therapy of infections caused by multi-drug resistant S. aureus strains.

摘要

本研究的目的是调查三种单萜类化合物橙花醇、二甲基辛醇和草蒿脑对细菌和酵母菌株的内在抗菌活性,以及研究这些化合物是否能够抑制金黄色葡萄球菌中与氟喹诺酮耐药性相关的NorA外排泵。通过微量稀释法测定单萜类化合物对金黄色葡萄球菌、大肠杆菌和白色念珠菌菌株的最低抑菌浓度(MIC)。在不存在或存在亚抑菌浓度的单萜类化合物的情况下,测定诺氟沙星对过表达NorA蛋白的金黄色葡萄球菌菌株的MIC,旨在验证该化合物作为外排泵抑制剂的能力。单萜类化合物对金黄色葡萄球菌无活性,然而橙花醇对大肠杆菌和白色念珠菌有活性。以亚抑菌浓度将这些化合物添加到生长培养基中可增强诺氟沙星对金黄色葡萄球菌SA1199-B的活性。该结果表明,所测试的生物活性物质,尤其是橙花醇,能够抑制NorA外排泵,表明其有可能用作诺氟沙星的佐剂,用于治疗由多重耐药金黄色葡萄球菌菌株引起的感染。

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