Morpholinium-based Ionic Liquids as Potent Antibiofilm and Sensitizing Agents for the Control of Pseudomonas aeruginosa

Rising antimicrobial resistance is a critical threat to worldwide public health. To address the increasing antibiotic tolerance, diverse antimicrobial agents are examined for their ability to decrease bacterial resistance. One of the most relevant and persistent human pathogens is Pseudomonas aeruginosa. Our study investigates the anti-biofilm and sensitizing activity of 12 morpholinium-based ionic liquids with herbicidal anions on four clinically relevant P. aeruginosa strains. Among all tested compounds, four ionic liquids prevented biofilm formation at sub-minimum inhibitory concentrations for all investigated strains. For the first time, we established a hormetic effect on biofilm formation for P. aeruginosa strains subjected to an ionic liquid treatment. Interestingly, while ionic liquids with 4,4-didecylmorpholinium [Dec2Mor]' are more efficient against planktonic bacteria, 4-decyl-4-ethylmorpholinium [DecEtMor]' showed more potent inhibition of biofilm formation. Ionic liquids with 4,4-didecylmorpholinium ([Dec2Mor]') cations even induced biofilm formation by strain 39016 at high concentrations due to flocculation. Morpholinium-based ionic liquids were also shown to enhance the efficacy of commonly used antibiotics from different chemical groups. We demonstrate that this synergy is associated with the mode of action of the antibiotics.