Antimicrobial mechanism of amino acid-based ionic liquids against E. coli, S. aureus, and C. neoformans: A multi-target and synergistic study

Abstract

In the context of increasingly severe antibiotic resistance, choline-amino acid ionic liquids ([Cho][AA] Bio-ILs) have attracted considerable attention as highly promising novel antimicrobial materials due to their excellent antimicrobial activity, against drug resistance, and biocompatibility. However, their antimicrobial mechanism remains unclear, with a notable scarcity of related research. Herein, the antimicrobial mechanisms of [Cho][AA] Bio-ILs against E. coli (Gram-negative bacteria), S. aureus (Gram-positive bacteria) and C. neoformans (fungi) were thoroughly investigated. Moreover, the mode of action, phase transition behavior, and thermodynamic behavior of [Cho][AA] Bio-ILs against microbial cells were also explored from the microscopic and molecular levels. The results indicated that the antimicrobial mechanism of [Cho][AA] Bio-ILs involved a synergistic effect of anions and cations. The structural characteristics of amino acid anions played an important role in regulating the antimicrobial activity of [Cho][AA] Bio-ILs. The potent broad-spectrum antimicrobial performance of [Cho][AA] Bio-ILs stemmed from their multi-target mechanism, which covered membrane disruption, metabolic inhibition, genetic damage, and oxidative stress. Importantly, the irreversible physical harm inflicted on the cell membrane decreased the likelihood of microbes developing resistance. These findings are expected to deepen our understanding of the antimicrobial mechanism of [Cho][AA] Bio-ILs, provide a theoretical basis for the rational design and application of these compounds, and offer new insights and strategies for addressing microbial infections and antibiotic resistance.