University of Veterinary Medicine Vienna Antimicrobial Ionic Liquids: Ante-Mortem Mechanisms of Pathogenic EPEC and MRSA Examined by FTIR Spectroscopy Ionic liquids (ILs) have gained considerable attention due to their versatile and designable properties. ILs show great potential as antibacterial agents, but understanding the mechanism of attack on bacterial cells is essential to ensure the optimal design of IL-based biocides. The final aim is to achieve maximum efficacy while minimising toxicity and preventing resistance development in target organisms. In this study, we examined a dose-response analysis of ILs' antimicrobial activity against two pathogenic bacteria with different Gram types in terms of molecular responses on a cellular level using Fourier-transform infrared (FTIR) spectroscopy. In total, 18 ILs with different antimicrobial active motifs were evaluated on the Gram-negative enteropathogenic Escherichia coli (EPEC) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). The results showed that most ILs impact bacterial proteins with increasing concentration but have a minimal effect on cellular membranes. Dose-response spectral analysis revealed a distinct ante-mortem response against certain ILs for MRSA but not for EPEC. We found that at sub-lethal concentrations, MRSA actively changed their membrane composition to counteract the damaging effect induced by the ILs. This suggests a new adaptive mechanism of Gram-positive bacteria against ILs and demonstrates the need for a better understanding before using such substances as novel antimicrobials. en TEXT article Methicillin-Resistant Staphylococcus aureusdrug effects; Ionic Liquidschemistrypharmacology; Spectroscopy, Fourier Transform Infraredmethods; Enteropathogenic Escherichia colidrug effects; Anti-Bacterial Agentspharmacologychemistry; Microbial Sensitivity Tests 2024 2024 Mikuni-Mester, Patrick (University of Veterinary Medicine Vienna / Austrian Competence Centre for Feed and Food Quality, Safety & Innovation) Grunert, Tom (University of Veterinary Medicine Vienna) Rossmanith, Peter (University of Veterinary Medicine Vienna) Ehling-Schulz, Monika (University of Veterinary Medicine Vienna) Linke, Kristina (ZuchtData EDV-Dienstleistungen GmbH) Witte, Anna K. (HTK Hygiene Technologie Kompetenzzentrum GmbH) Robben, Christian (University of Veterinary Medicine Vienna) MDPI