Synergistic activity between colistin and the ionic liquids 1-methyl-3 dodecylimidazolium bromide, 1-dodecyl-1-methylpyrrolidinium bromide, or 1 dodecyl-1-methylpiperidinium bromide against Gram-negative bacteria

Objectives 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 sustained 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 asEscherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Methods The interaction between colistin and ionic liquids against Gram-negative bacteria was evaluated by the checkerboard assay. Bacterial killing assays againstP. aeruginosa were carried out to assess whether the synergistic combinations were bactericidal. Results The results of checkerboard assays showed that all three ionic liquids interacted synergistically with colistin againstK. pneumoniae, P. aeruginosa, and A. baumannii but not against Escherichia coli, which resulted more sensitive to all three ionic liquids compared to the other tested species. The synergistic combinations showed no hemolytic 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. Conclusion Overall, the results obtained suggest that colistin and ionic liquids might be used in combination for possible applications to combat infections sustained by multi-drug resistant Gram-negative bacteria.