Antimicrobial potential of the food-grade additive carvacrol against uropathogenic E. coli based on membrane depolarization, reactive oxygen species generation, and molecular docking analysis

The antibiotic resistance of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has increased drastically in recent years. In our study, we determined the principle mechanisms of action for the food-grade additive carvacrol against ESBL E. coli isolated from the blood of patients with a urinary tract infection. Carvacrol, which has a minimum inhibitory concentration of 150 mu g/ml and a minimum bactericidal concentration of 300 mu g/ml, reduced E. coli cell counts in a time-dependent manner. After treatment with carvacrol, the E. coli killing time was found to be 120 min. Fluorescent staining confirmed an increase in bacterial cell death, greater membrane depolarization, and an elevated oxidative burst in carvacrol-treated E. coli. Carvacrol also induced the release of cellular DNA, proteins, and potassium ions from bacterial cells and reduced both the number of E. coli in invasion assays against macrophages and the levels of the inflammatory proteins TNF-alpha and COX-2. In addition, carvacrol was found to inhibit beta-lactamase enzyme activity (in vitro), which was supported by in silico results. Moreover, carvacrol inhibited motility, and protected against bacterial invasion. Overall, the findings suggest that carvacrol has significant antimicrobial potential against ESBL E. coli.