Improved Antibacterial Activity of Peptide Nisin with Pyrrole-Based Ionic Liquids Having Bis(trifluoromethylsulfonyl)imide as a Counterion: A Synergistic Approach to Combat Bacterial Infections.

ABSTRACT

Bacterial resistance against antimicrobial drugs is a forthcoming threat to the prevention and treatment of developing bacterial infections. Hence, the development of new antimicrobial therapy or therapeutic drugs is desperately needed. A combination of antibiotics exhibits synergistic antibacterial effects. As the combination approach of antibiotics has always shown better results against pathogens compared to monotherapy with an antibiotic, we focused on creating a new combination that may reduce the chances of strains attaining resistance, consequently lowering the toxicity factor associated with the consumption of high amounts of antibiotics. Nisin, a food preservative and potential antibiotic, shows antibacterial activity against Gram-positive strains. Since the past decade, ionic liquids (ILs) have proven to be an important class of potential antibacterial agents. In our study, we studied the effect of pyrrolidinium-based ILs and arrived at a noncovalent conjugate formed by combining nisin with ILs. The conjugates were tested against a couple of clinically relevant microorganisms, namely, Escherichia coli and Staphylococcus aureus. We reached a novel discovery that the combination of sodium/iodide symporter (NIS) and IL exhibited inhibitory effects against Gram-negative bacteria, which was not observed with NIS alone. The results showed remarkable improvement in the minimum inhibitory concentration (MIC) value of NIS in the presence of ILs targeted against both microorganisms. Further, flow cytometry and confocal microscopy results revealed the membrane disruption efficiency of the best combination obtained, leading to cell death. Additionally, the complexation of nisin and ILs was studied using various techniques, such as surface tension, dynamic light scattering, absorption spectroscopy, and molecular docking.