Organic acid-based deep eutectic solvents (DESs) are potent antimicrobial agents against antibiotic-resistant...

The escalating threat of antibiotic-resistant bacteria, biofilms and viral contamination in the healthcare and food industries threatens global health and requires the development of innovative antimicrobials. Deep eutectic solvents (DESs) have attracted attention as antimicrobial candidates, but there is little data on their effectiveness against antibiotic-resistant bacteria and viruses. This study evaluated the effectiveness of two organic acid-based DESs (T-glycoline and oxaline) and two non-organic acid-based DESs (reline and glyceline) against antibiotic-resistant Gram-positive and Gram-negative bacteria, as well as enveloped and non-enveloped viruses. Organic acid-based deep eutectic solvents outperformed their non-organic counterparts, achieving minimum inhibitory concentrations (MICs) of 0.20-0.83% v/v. T-glycoline and oxaline demonstrated synergy against colistin-resistant Enterobacterales, reducing the expression of the mobilised colistin resistance (mcr) gene. Combining T-glycoline with alginate/starch nanoparticles increased effectiveness against methicillin-resistant Staphylococcus aureus (MRSA). Organic DESs eradicated mature biofilms. Confocal microscopy revealed large numbers of dead bacterial cells, while transmission electron microscopy (TEM) showed cytoplasmic disruption. Combining alginate NPs with T-glycoline increased Caco-2 viability to 95% (compared to 15% with T-glycoline alone). T-glycoline and oxaline drastically reduced the infectious titres of both enveloped and non-enveloped viruses. Overall, these findings suggested that selected DES formulations may have potential as antimicrobial candidates, although their safety should be considered in practical applications.