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
Affiliations
Daniel D. Yang
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA
Nicholas J. Paterna
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA
Alexandria S. Senetra
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA
Kaitlyn R. Casey
Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA
Phillip D. Trieu
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA
Gregory A. Caputo
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA; Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA
Timothy D. Vaden
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA
Benjamin R. Carone
Department of Molecular and Cellular Biosciences, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, USA; Corresponding author
Summary: 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.
