Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant bacteria

Plant-derived antibacterial compounds may be of value as a novel means for controlling antibiotic resistant zoonotic pathogens which contaminate food animals and their products. Individual activity of natural antimicrobials (eugenol, thymol, carvacrol, cinnamaldehyde, allyl isothiocyanate (AIT)) and activity when paired with an antibiotic was studied using broth microdilution and checkerboard methods. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interactions between the inhibitors. Bacteria tested were chosen because of their resistance to at least one antibiotic which had a known genetic basis. Substantial susceptibility of these bacteria toward the natural antimicrobials and a considerable reduction in the minimum inhibitory concentrations (MICʹs) of the antibiotics were noted when paired combinations of antimicrobial and antibiotic were used. In the interaction study, thymol and carvacrol were found to be highly effective in reducing the resistance of Salmonella Typhimurium SGI 1 (tet A) to ampicillin, tetracycline, penicillin, bacitracin, erythromycin and novobiocin (FIC < 0.4) and resistance of Streptococcus pyogenes ermB to erythromycin (FIC < 0.5). With Escherichia coli N00 666, thymol and cinnamaldehyde were found to have a similar effect (FIC < 0.4) in reducing the MICʹs of ampicillin, tetracycline, penicillin, erythromycin and novobiocin. Carvacrol, thymol (FIC < 0.3) and cinnamaldehyde (FIC < 0.4) were effective against Staphylococcus aureus blaZ and in reducing the MICʹs of ampicillin, penicillin and bacitracin. Allyl isothiocyanate (AIT) was effective in reducing the MIC of erythromycin (FIC < 0.3) when tested against S. pyogenes. Fewer combinations were found to be synergistic when the decrease in viable population (log DP) was calculated. Together, fractional inhibitory concentrations ≤ 0.5 and log DP < − 1 indicated synergistic action between four natural antimicrobials and as many as three antibiotics to which these bacteria were normally resistant.