Intrinsic insights to antimicrobial effects of Nitrofurantoin to multi drug resistant Salmonella enterica serovar Typhimurium ms202

Abstract

Emerging multidrug resistant (MDR) serovar of Salmonella has raised the concern of their impactful effect on pathogenic infection and mortality in human lead by the enteric diseases. In order to combat the battle against these MDR Salmonella pathogen, new drug molecules need to be evaluated for their potent antibacterial application. This study evaluates the mechanistic antimicrobial effect of nitrofurantoin against a MDR strain of Salmonella named S. enterica Typhimurium ms202. The antimicrobial effect of nitrofurantoin was studied through experimental and computational approach using standard microbiological and molecular techniques like growth curve analysis, live-dead analysis, oxidative stress evaluation using high throughput techniques like flow cytometry and fluorescent microscopy. The result showed a potent dose dependent antibacterial effect of nitrofurantoin against S. enterica Typhimurium ms202 with a MIC value of 64 µg/ml. Moreover, the mechanistic excavation of the phenomenon described the mechanism as an effect of molecular interaction of nitrofurantoin molecule with membrane receptor proteins OmpC of S. enterica Typhimurium ms202 leading to internalization of the nitrofurantoin heading towards the occurrence of cellular physiological disturbances through oxidative stress impeded by nitrofurantoin-Sod1 C protein interaction. The results indicated towards a synergistic effect of membrane damage, oxidative stress and genotoxicity for the antibacterial effect of nitrofurantoin against S. enterica Typhimurium ms202. The study described the potent dose-dependent application of nitrofurantoin molecule against MDR strains of Salmonella and guided towards their use in further discovered MDR strains.

Keywords: Multidrug resistant; Nitrofurantoin; Oxidative stress; Salmonella.