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纳米颗粒包裹的姜黄素通过下调外排泵对铜绿假单胞菌临床分离株的抗菌作用

Antibacterial effects of curcumin encapsulated in nanoparticles on clinical isolates of Pseudomonas aeruginosa through downregulation of efflux pumps.

作者信息

Rahbar Takrami Saeid, Ranji Najmeh, Sadeghizadeh Majid

机构信息

Department of Biology, Faculty of Science, Rasht Branch, Islamic Azad University, P.O. Box 41235-3516, Rasht, Iran.

Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Mol Biol Rep. 2019 Apr;46(2):2395-2404. doi: 10.1007/s11033-019-04700-2. Epub 2019 Feb 18.

DOI:10.1007/s11033-019-04700-2
PMID:30778922
Abstract

Curcumin as a flavonoid from the rhizome of Curcuma longa has antibacterial, antiviral and antifungal activity. Multidrug resistance in pathogenic bacteria is continuously increasing in hospitals. The aim of this study was to investigate the effect of curcumin encapsulated in micellar/polymersome nanoparticles as an efflux pump inhibitor (EPI) on the expression of mexX and oprM genes in curcumin-treated and -untreated isolates of Pseudomonas aeruginosa. Clinical isolates of Pseudomonas aeruginosa were treated with ciprofloxacin (sub-MICs) alone and/or in combination with curcumin-encapsulated in micellar/polymersome nanoparticles. The expression of mexX and oprM genes was quantitatively evaluated by qRT-PCR in curcumin-treated and -untreated bacteria after 24 h. Curcumin-encapsulated in nanoparticles (400 µg/mL) induced cell death up to 50% in ciprofloxacin-treated (1/2MIC) resistant isolates during 24 h, while the bacteria treated with ciprofloxacin (without curcumin) were not inhibited. Also, curcumin in different concentrations increased effect of ciprofloxacin (sub-MICs). Downregulation of mexX and oprM genes was observed in cells treated with curcumin and ciprofloxacin compared to cells treated with ciprofloxacin alone. It seems that curcumin can be used as complementary drug in ciprofloxacin-resistant isolates through downregulating genes involved in efflux pumps and trapping ciprofloxacin on bacterial cells and increasing the effects of drug.

摘要

姜黄素作为一种从姜黄根茎中提取的黄酮类化合物,具有抗菌、抗病毒和抗真菌活性。医院中病原菌的多重耐药性正在持续增加。本研究的目的是调查包裹在胶束/聚合物囊泡纳米颗粒中的姜黄素作为一种外排泵抑制剂(EPI),对经姜黄素处理和未处理的铜绿假单胞菌分离株中mexX和oprM基因表达的影响。铜绿假单胞菌的临床分离株分别单独用环丙沙星(亚最小抑菌浓度)和/或与包裹在胶束/聚合物囊泡纳米颗粒中的姜黄素联合处理。24小时后,通过qRT-PCR对经姜黄素处理和未处理的细菌中mexX和oprM基因的表达进行定量评估。在24小时内,包裹在纳米颗粒中的姜黄素(400µg/mL)在环丙沙星处理(1/2MIC)的耐药分离株中诱导高达50%的细胞死亡,而用环丙沙星(无姜黄素)处理的细菌未受到抑制。此外,不同浓度的姜黄素增强了环丙沙星(亚最小抑菌浓度)的作用。与单独用环丙沙星处理的细胞相比,在用姜黄素和环丙沙星处理的细胞中观察到mexX和oprM基因的下调。似乎姜黄素可以通过下调参与外排泵的基因、将环丙沙星捕获在细菌细胞上并增强药物作用,用作耐环丙沙星分离株的辅助药物。

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Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants.细菌多药外排泵:远不止是抗生素耐药性决定因素
Microorganisms. 2016 Feb 16;4(1):14. doi: 10.3390/microorganisms4010014.
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