Florio Walter, Rizzato Cosmeri, Becherini Stefano, Guazzelli Lorenzo, D'Andrea Felicia, Lupetti Antonella
Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Via San Zeno 37-39, 56127, Pisa, Italy.
Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 6, 56126, Pisa, Italy.
J Glob Antimicrob Resist. 2020 Jun;21:99-104. doi: 10.1016/j.jgar.2020.03.022. Epub 2020 Apr 13.
Ionic liquids have shown potential for applications as antimicrobials. Their antimicrobial activity has been shown to be higher against Gram-positive than Gram-negative bacteria, suggesting a protective role for the outer membrane of Gram-negative microorganisms. Colistin is a last-resort antibiotic often used for treating infections caused by multi-drug resistant Gram-negative bacteria. Colistin interacts with the bacterial lipopolysaccharide, thus altering the structure and increasing the permeability of the outer membrane. The aim of this study was to investigate the interaction between colistin and the ionic liquids 1-methyl-3-dodecylimidazolium bromide, 1-dodecyl-1-methylpyrrolidinium bromide, and 1-dodecyl-1-methylpiperidinium bromide against Gram-negative bacteria of clinical importance such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii.
The interaction between colistin and ionic liquids against Gram-negative bacteria was evaluated by the checkerboard assay. Bacterial killing assays against P. aeruginosa were carried out to assess whether the synergistic combinations were bactericidal.
The results of checkerboard assays showed that all three ionic liquids interacted synergistically with colistin against K. pneumoniae, P. aeruginosa, and A. baumannii but not against E. coli, which was more sensitive to all three ionic liquids compared with the other tested species. The synergistic combinations showed no haemolytic activity. Bacterial killing assays showed that the synergistic effect between colistin and each one of the three tested ionic liquids against P. aeruginosa was bactericidal.
Overall, the results obtained suggest that colistin and ionic liquids might be used in combination for possible applications to combat infections caused by multi-drug resistant Gram-negative bacteria.
离子液体已显示出作为抗菌剂的应用潜力。它们对革兰氏阳性菌的抗菌活性高于革兰氏阴性菌，这表明革兰氏阴性微生物的外膜具有保护作用。黏菌素是一种常用于治疗多重耐药革兰氏阴性菌引起的感染的最后手段抗生素。黏菌素与细菌脂多糖相互作用，从而改变外膜结构并增加其通透性。本研究的目的是调查黏菌素与离子液体1-甲基-3-十二烷基咪唑溴盐、1-十二烷基-1-甲基吡咯烷溴盐和1-十二烷基-1-甲基哌啶溴盐对具有临床重要性的革兰氏阴性菌（如大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌）之间的相互作用。
通过棋盘法评估黏菌素与离子液体对革兰氏阴性菌的相互作用。对铜绿假单胞菌进行细菌杀灭试验，以评估协同组合是否具有杀菌作用。
棋盘法结果表明，所有三种离子液体与黏菌素对肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌均有协同作用，但对大肠杆菌无协同作用，与其他受试菌种相比，大肠杆菌对所有三种离子液体更敏感。协同组合无溶血活性。细菌杀灭试验表明，黏菌素与三种受试离子液体中的每一种对铜绿假单胞菌的协同作用均具有杀菌作用。
总体而言，所得结果表明，黏菌素和离子液体可能联合用于对抗多重耐药革兰氏阴性菌引起的感染。
