Ciprofloxacin-based ionic liquids demonstrate increased mutation frequency in Escherichia coli

Abstract

In the last decade, development of active pharmaceutical ingredient ionic liquids (API-ILs) has been proposed as a prospective game-changing strategy to overcome multiple problems with conventional solid-state drugs. Formulation of antibiotics as API-ILs has been reported to improve physico-chemical parameters as well as possible synergistic effects overcoming antimicrobial resistance. What has not been assessed to date however are possible adverse effects of the API-ILs considering the potentially wide-scale application and the inevitable release to the environment, as is the case with antibiotics and other popular medications. In this study, API-ILs based on the antibiotic ciprofloxacin were synthesized and investigated in terms of their antimicrobial activity and influence on mutation frequency of Escherichia coli MG1655. This is the first report that by formulating of antibiotics as API-ILs, bacterial mutation frequencies can be significantly increased, while structurally similar chloride ILs alone do not have such an effect. The observed changes in mutation frequencies seem to be dependent on the structure of the respective counterion. As increased mutation frequencies can fuel adaptation and ultimately resistance development of bacteria, it is crucial to improve our understanding of how API-ILs can designed in a safer way.