Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy

Daniel D Yang; Nicholas J Paterna; Alexandria S Senetra; Kaitlyn R Casey; Phillip D Trieu; Gregory A Caputo; Timothy D Vaden; Benjamin R Carone

doi:10.1016/j.isci.2020.101853

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy

iScience. 2020 Nov 23;24(1):101853. doi: 10.1016/j.isci.2020.101853. eCollection 2021 Jan 22.

Authors

Daniel D Yang¹, Nicholas J Paterna¹, Alexandria S Senetra¹, Kaitlyn R Casey², Phillip D Trieu¹, Gregory A Caputo^{1

2}, Timothy D Vaden¹, Benjamin R Carone²

Affiliations

¹ Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA.
² Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA.

Abstract

Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model.

Keywords: Biochemistry; Biological Sciences; Biophysics; Chemistry; Microbiology.