Bactericidal Properties of Dicationic Imidazolium Surfactants: A Comprehensive Study of Membranotropic Effects, Antibiofilm Activity, and Genotoxicity Safety

In Russia, antimicrobial resistance is a major cause of high mortality from infectious diseases. This problem is aggravated by a shortage of new antibiotics and inefficiency of the existing treatment schemes. This work investigates the antimicrobial and antibiofilm activity of dicationic imidazolium surfactants 10-2-10 (Im) and 12-2-12 (Im) against Staphylococcus aureus. It was shown that the compound 10-2-10 (Im) had a higher efficacy, inhibiting biofilm formation and completely destroying mature biofilms. The studied surfactants were found to exhibit a membranotropic activity, causing depolarization and permeabilization of the cytoplasmic membrane; however, these effects were observed at the concentrations significantly exceeding the MIC, which may indicate another specific mechanism of action. The key result is the low potential for development of resistance to compound 10-2-10 (Im): after 17 transfers, no significant increase in MIC was recorded, in contrast to the reference antibiotics. The Ames test revealed that 10-2-10 (Im) did not possess a mutagenic activity, while 12-2-12 (Im) induced frameshift mutations at high concentrations. The compound 10-2-10 (Im) was shown to be a promising agent for the treatment of S. aureus biofilm infections due to its comprehensive action, low risk of resistance development, and absence of mutagenicity.