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白藜芦醇作为群体感应抑制剂,是否可以作为氨基糖苷类抗生素增效剂对抗铜绿假单胞菌?

Can the quorum sensing inhibitor resveratrol function as an aminoglycoside antibiotic accelerant against Pseudomonas aeruginosa?

机构信息

State Key Laboratory of Marine Resource Utilization in South China Sea, Key Laboratory of Tropical Biological Resources of Ministry Education, Hainan University, Haikou 570228, China; School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.

School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.

出版信息

Int J Antimicrob Agents. 2018 Jul;52(1):35-41. doi: 10.1016/j.ijantimicag.2018.03.002. Epub 2018 Mar 9.

DOI:10.1016/j.ijantimicag.2018.03.002
PMID:29530588
Abstract

Pseudomonas aeruginosa infection is a serious disease in cystic fibrosis patients and is difficult to treat owing to biofilm persistence and emerging multidrug resistance. Considering the essential role of quorum sensing (QS) in P. aeruginosa infections, the enhanced effects between the quorum sensing inhibitor (QSI) resveratrol and several antibiotics against P. aeruginosa PAO1 were investigated. Crystal violet staining assay revealed that biofilms of P. aeruginosa PAO1 grown in the presence of resveratrol were more susceptible to aminoglycoside antibiotics. Scanning electron and fluorescence microscopy showed architectural disruption of the biofilms when treated with resveratrol and aminoglycoside antibiotics. Furthermore, quantitative reverse transcription PCR (qRT-PCR) analysis demonstrated that expression of lasI and rhlI, two genes encoding enzymes that synthesise signal molecules in QS systems, were inhibited in the P. aeruginosa PAO1 biofilms by resveratrol. These results indicate that the QSI resveratrol can significantly enhance the effects of aminoglycoside antibiotics (e.g. tobramycin, gentamicin, amikacin and netilmicin) on P. aeruginosa PAO1 biofilms. These findings suggest that resveratrol is a potential accelerant in the treatment of P. aeruginosa biofilms and can restore or enhance the efficacy of aminoglycoside antibiotics.

摘要

铜绿假单胞菌感染是囊性纤维化患者的严重疾病,由于生物膜的持续存在和新兴的多药耐药性,治疗变得困难。鉴于群体感应(QS)在铜绿假单胞菌感染中的重要作用,研究了群体感应抑制剂(QSI)白藜芦醇与几种抗生素对铜绿假单胞菌 PAO1 的增强作用。结晶紫染色试验表明,在白藜芦醇存在下生长的铜绿假单胞菌 PAO1 生物膜对氨基糖苷类抗生素更敏感。扫描电子显微镜和荧光显微镜显示,当用白藜芦醇和氨基糖苷类抗生素处理时,生物膜的结构被破坏。此外,定量逆转录 PCR(qRT-PCR)分析表明,白藜芦醇抑制了铜绿假单胞菌 PAO1 生物膜中 lasI 和 rhlI 两种基因的表达,这两个基因编码 QS 系统中合成信号分子的酶。这些结果表明,QS 抑制剂白藜芦醇可以显著增强氨基糖苷类抗生素(如妥布霉素、庆大霉素、阿米卡星和奈替米星)对铜绿假单胞菌 PAO1 生物膜的作用。这些发现表明,白藜芦醇是治疗铜绿假单胞菌生物膜的潜在加速剂,可以恢复或增强氨基糖苷类抗生素的疗效。

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