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Morpholinium-based Ionic Liquids as Potent Antibiofilm and Sensitizing Agents for the Control of Pseudomonas
Jakub Michalski1, Tomasz Cłapa1, Dorota Narożna1
1Poznań University of Life Sciences, Department of Biochemistry and Biotechnology, Dojazd 11, 60-632 Poznan, Poland.
Abstract:
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.
Insights
Ionic liquids show promise in combating Pseudomonas aeruginosa biofilms and enhancing antibiotic effectiveness. This study reveals their potential to overcome antimicrobial resistance and offers new strategies for infection control.
Area of Science:
- Microbiology
- Medicinal Chemistry
- Materials Science
Background:
- Antimicrobial resistance, particularly in Pseudomonas aeruginosa, poses a significant global health threat.
- Developing novel agents to combat antibiotic tolerance and biofilm formation is crucial.
Purpose of the Study:
- To investigate the anti-biofilm and antibiotic-sensitizing properties of morpholinium-based ionic liquids against Pseudomonas aeruginosa.
- To explore the potential of ionic liquids in overcoming antimicrobial resistance.
Main Methods:
- Testing 12 morpholinium-based ionic liquids with herbicidal anions on four clinical P. aeruginosa strains.
- Assessing biofilm inhibition, planktonic bacterial growth, and antibiotic synergy.
- Investigating the hormetic effect and concentration-dependent impacts of ionic liquids.
Main Results:
- Four ionic liquids effectively prevented biofilm formation at sub-minimum inhibitory concentrations.
- A hormetic effect on biofilm formation was observed for the first time in P. aeruginosa.
- Specific ionic liquids demonstrated differential activity against planktonic bacteria versus biofilms.
- Ionic liquids enhanced the efficacy of various antibiotics, suggesting synergistic interactions.
Conclusions:
- Morpholinium-based ionic liquids are effective against P. aeruginosa biofilms and can resensitize bacteria to antibiotics.
- Ionic liquids offer a promising strategy to combat antimicrobial resistance and improve treatment outcomes.
- Further research into ionic liquid mechanisms and applications in antimicrobial therapy is warranted.
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