Quorum sensing (QS) inhibition by metal-antibiotic complexes is a promising strategy for the management and control of multidrug resistant Pseudomonas aeruginosa infections. We investigated the anti-quorum sensing activity of sub-minimum inhibitory concentration (sub-MIC) of copper(II) sulfate pentahydrate-ciprofloxacin (Cu-CIP) complex and free ciprofloxacin (free-CIP) against P. aeruginosa PAO1. Copper-CIP complex was synthesized and its characterization was assessed using spectroscopic methods and single crystal X-ray analysis. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of Cu-CIP and free-CIP on cell growth, biofilm formation, motility, alginate and pyocyanin production, H2O2 susceptibility and expression of QS circuit genes lasI and lasR in PAO1 was determined. Minimum inhibitory concentration of Cu-CIP complex and free-CIP was determined as 0.125 µg/ml. Copper-CIP complex did not show significant effect on the cell growth at concentrations of 1/4 and 1/16 MIC. However, sub-MIC concentrations (1/4 and 1/16 MIC) of Cu-CIP showed the significant reduction in violacein production, motility, biofilm formation, alginate and pyocyanin production and sensitivity to H2O2 in a concentration dependent manner (P < 0.001). Copper-CIP at the concentration of 1/4 MIC showed the greatest reduction in lasI and lasR transcriptional expression (89.5% and 96.2% respectively). Considering the biological effects of Cu-CIP complex and its inhibitory activity on QS related virulence traits at low concentrations (0.03 and 0.007 µg/ml), it may be used as an effective approach in the management of infections caused by P. aeruginosa.

中文翻译：

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铜（II）-环丙沙星复合物对铜绿假单胞菌PAO1的合成，表征和抗群体感应活性的评估。

金属-抗生素复合物抑制群体感应（QS）是管理和控制多药耐药性铜绿假单胞菌感染的一种有前途的策略。我们研究了五水硫酸铜（II）五水合环丙沙星（Cu-CIP）复合物和游离环丙沙星（free-CIP）对铜绿假单胞菌PAO1的最低抑制浓度（sub-MIC）的抗群体感应活性。合成了铜-CIP配合物，并使用光谱法和单晶X射线分析评估了其特征。亚MIC（1/4和1/16 MIC）浓度的Cu-CIP和游离CIP对细胞生长，生物膜形成，运动性，藻酸盐和绿脓素生成，H2O2敏感性以及QS电路基因lasI和lasR的表达的影响确定在PAO1中。Cu-CIP复合物和游离CIP的最小抑菌浓度确定为0.125 µg / ml。铜-CIP复合物在1/4和1/16 MIC浓度下对细胞生长没有显着影响。但是，Cu-CIP的亚MIC浓度（1/4和1/16 MIC）显示出紫胶生成，运动性，生物膜形成，藻酸盐和绿脓素生成以及对H2O2的敏感性显着降低（P <0.001） ）。在1/4 MIC浓度下，Copper-CIP的lasI和lasR转录表达下降最大（分别为89.5％和96.2％）。考虑到低浓度（0.03和0.007 µg / ml）下的Cu-CIP复合物的生物学效应及其对QS相关毒力特性的抑制活性，它可以用作治疗由P引起的感染的有效方法。