Assessment of antimicrobial potential of antibiotics augmented dibutyl 10 ammonium leucinate ionic liquid against pathogenic bacteria

Abstract

The problem of growing antibiotic resistance of pathogenic bacteria in the human body is one of the principal challenges of modern healthcare and hence the search for new antimicrobial agents is a very important task. In this study di-butyl 10 ammonium leucinate (DBAL) were synthesized, characterized, and evaluated for their antimicrobial activities as a potential alternative or adjunct to conventional antibiotics. We subsequently synthesized, structurally characterized DBAL through fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy and confirmed the design of the key functional groups responsible for DBAL's antimicrobial activity. Solubility profile of DBAL was found to be compatible with polar solvents that might be useful in pharmaceutical formulation. We assessed the antimicrobial efficacy of DBAL against a variety of Gram-positive and Gramnegative bacterial strains (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecalis, Acinetobacter baumannii, Salmonella enterica, and Lactobacillus rhamnosus). On the basis of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, it exhibited broad spectrum antibacterial activity on all tested human pathogens with Salmonella enterica as the most susceptible. Furthermore, DBAL possessed significant antibiofilm efficacy against uropathogenic Escherichia coli strains which is of great importance for chronic infection and antibiotic resistance. One such aspect of the study was probing DBAL’s synergestic interactions with conventional antibiotics (ciprofloxacin and doxycycline). The electronic microscopy , Gram staining , agar well diffusion assays , and disc diffusion assays suggested additive bactericidal and bacteriostatic effects, while the Fractional Inhibitory Concentration Index (FICI) and disc diffusion assays yielded quantitative evidence for the increased efficacy of DBAL in combination with antibiotics. The observed synergy indicates that DBAL may enhance antibiotic activity by mechanisms including damage of bacterial membrane and inhibition of efflux pump. In albino mouse model , further in vivo evaluation revealed biocompatible DBAL with no evidence of dermal reaction or sensitization. Furthermore, the DBAL enhanced antibiotic formulations accelerated wound healing as shown by improved hematological parameters. Results suggest DBAL has promising potential as an antimicrobial agent and adjunctive therapy to available antibiotics to address antibiotic resistance . The potential of ionic liquids for antimicrobial applications is highlighted by this research as a foundation to explore DBAL’s mechanisms of action, clinical applicability, and formulation development . This study demonstrates for the first time the use of DBAL as a novel approach for the enhancement of antibacterial efficacy in conjunction with conventional antibiotics in an effort to resolve the immediate need for new therapeutic strategies for infections caused by drug resistant pathogens.