Influence of bacterial lipopolysaccharide modifications on the efficacy of antimicrobial ionic liquids

The increasing industrial use of ionic liquids (ILs) now demands accurate (eco)toxicological evaluations based on their structural composition. Although bacteria are major test organisms for this research, fundamental bacterial resistance mechanisms against antimicrobial ILs have been neglected. This deficiency could hamper interpretation of related experimental findings. Among the most important resistance mechanisms encountered in bacteria are cell membrane modifications, which can hinder the entry of antimicrobials such antibiotics or quaternary ammonium compounds (QACs). This study investigates the role of lipopolysaccharides (LPS), a major component of the outer leaflet of Gram-negative bacteria, and modifications of its length on the IL activities using three different single-gene deletion mutants of E. coli K-12. In total, 19 different ILs, covering various structural motifs as well as active pharmaceutical ILs (API-ILs) based on the intracellular operating antibiotic nalidixic acid were investigated. Results reveal that, while known structure-activity relationships (SARs), such as the side-chain effect, were relevant for all tested strains, decreasing the LPS length leads to a higher susceptibilities to antimicrobial ILs as well as API-ILs. These findings highlight the importance of considering membrane changes, such as LPS modification, as important bacterial defense mechanisms.