Mechanism of Antibacterial Activity of Choline-Based Ionic Liquids (CAGE)

Kelly N. Ibsen, Huilin Ma, Amrita Banerjee, Eden E.L. Tanner, Shikha Nangia, Samir Mitragotri

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The continued emergence of antibiotic-resistant organisms has severely depleted our arsenal of effective antimicrobials. Ionic liquids (ILs) show great promise as antibacterial agents but understanding the mechanism of attack on bacterial cells is key to ensuring that design of IL-based biocides impart maximum efficacy with minimal toxicity, while also avoiding the potential for the target organisms to become resistant. Here we report the antibacterial attributes of a set of choline and geranate (CAGE)-based ILs and identify the mechanism by which they interact with the Gram-negative cell wall of Escherichia coli. CAGE is envisaged as an antimicrobial agent to treat topical infections in skin. Our earlier work has shown that CAGE is highly effective across a breadth of bacterial, fungal, and viral species and is benign to human cells. This combination makes CAGE an ideal antimicrobial for human use. Four CAGE variants with varying ratios of choline and geranic acid were synthesized and tested for their antibacterial activity (1:4, 1:2, 1:1, and 2:1 choline:geranic acid). The minimum bactericidal concentration required to kill E. coli correlated with the geranic acid content. Using molecular dynamics (MD) simulations, we identified the mechanism of CAGE action on the E. coli membrane, namely that choline is attracted to the negatively charged cell membrane and consequently inserts geranic acid into the lipid bilayer. The disruption of the cell membrane was confirmed with propidium iodide staining via flow cytometry and scanning electron microscopy. Fourier Transform infrared spectroscopic analysis of treated cells showed an altered lipid profile similar to phase transition, indicating the disruption of the lipid bilayer conformation. E. coli cells repeatedly exposed to CAGE did not exhibit resistance. This study provides the fundamental mechanism of the action of choline-based ILs on Gram-negative bacteria and demonstrates the promise of CAGE as a powerful antimicrobial agent to treat infections.

Original languageEnglish (US)
Pages (from-to)2370-2379
Number of pages10
JournalACS Biomaterials Science and Engineering
Volume4
Issue number7
DOIs
StatePublished - Jul 9 2018

Fingerprint

Ionic Liquids
Choline
Ionic liquids
Escherichia coli
Antimicrobial agents
Lipid bilayers
Acids
Cells
Cell membranes
Anti-Infective Agents
Arsenals
Anti-Bacterial Agents
Bactericides
Biocides
Spectroscopic analysis
Flow cytometry
Propidium
Disinfectants
Antibiotics
Lipids

Keywords

  • antibacterial
  • ionic liquid
  • membrane disruption
  • molecular dynamics simulation

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

Cite this

Mechanism of Antibacterial Activity of Choline-Based Ionic Liquids (CAGE). / Ibsen, Kelly N.; Ma, Huilin; Banerjee, Amrita; Tanner, Eden E.L.; Nangia, Shikha; Mitragotri, Samir.

In: ACS Biomaterials Science and Engineering, Vol. 4, No. 7, 09.07.2018, p. 2370-2379.

Research output: Contribution to journalArticle

Ibsen, Kelly N. ; Ma, Huilin ; Banerjee, Amrita ; Tanner, Eden E.L. ; Nangia, Shikha ; Mitragotri, Samir. / Mechanism of Antibacterial Activity of Choline-Based Ionic Liquids (CAGE). In: ACS Biomaterials Science and Engineering. 2018 ; Vol. 4, No. 7. pp. 2370-2379.
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