https://phaidra.vetmeduni.ac.at/o:3623 Antimicrobial Ionic Liquids: Ante-Mortem Mechanisms of Pathogenic EPEC and MRSA Examined by FTIR Spectroscopy Mikuni-Mester, Patrick Patrick Mikuni-Mester 0000-0002-3193-4987 University of Veterinary Medicine Vienna / Austrian Competence Centre for Feed and Food Quality, Safety & Innovation Grunert, Tom Tom Grunert 0000-0001-5722-6631 University of Veterinary Medicine Vienna Rossmanith, Peter Peter Rossmanith University of Veterinary Medicine Vienna Ehling-Schulz, Monika Monika Ehling-Schulz 0000-0001-7384-0594 University of Veterinary Medicine Vienna Linke, Kristina Kristina Linke 0009-0006-5582-8691 ZuchtData EDV-Dienstleistungen GmbH Witte, Anna K. Anna K. Witte HTK Hygiene Technologie Kompetenzzentrum GmbH Robben, Christian Christian Robben University of Veterinary Medicine Vienna MDPI text eng 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. Methicillin-Resistant Staphylococcus aureusdrug effects; Ionic Liquidschemistrypharmacology; Spectroscopy, Fourier Transform Infraredmethods; Enteropathogenic Escherichia colidrug effects; Anti-Bacterial Agentspharmacologychemistry; Microbial Sensitivity Tests http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:3623/download 10.3390/ijms25094705 https://phaidra.vetmeduni.ac.at/o:605 application/pdf International Journal of Molecular Sciences 25(9) (2024) International Journal of Molecular Sciences 25 9 2.25 MB 2024