Evaluation of the effects of galbanic acid from Ferula szowitsiana and conferol from F. badrakema, as modulators of multi-drug resistance in clinical isolates of Escherichia coli and Staphylococcus aureus

Galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana, and conferol, another sesquiterpene coumarin from F. badrakema, were evaluated for their effects on the reversal of multi-drug resistance in clinical isolates of Staphylococcus aureus and Escherichia coli, respectively. Neither galbanic acid (up to 1000 μg/ml) nor conferol (up to 400 μg/ml) by itself shows any antibacterial activities against tested strains. The minimum inhibitory concentrations (MICs) of ciprofloxacin and tetracycline were determined using macrodilution technique in the presence and absence of sub-inhibitory concentrations of galbanic acid (31.25-1000 μg/ml) or conferol (50-400 μg/ml), however they caused no change in MICs of the antibiotics. Galbanic acid did not show any inhibitory effect on efflux phenomenon of E. coli. This can be related to the outer membrane of gram-negative bacteria which is impermeable to lipophilic compounds or another mechanism rather than efflux responsible for resistance in tested E. coli strains. An inhibitory effect of conferol on the efflux was compared with verapamil as a positive control. Because efflux is the only known mechanism of resistance to ethidium bromide (model efflux substrate) and verapamil reduced MIC of ethidium bromide, efflux mechanism can be considered as one of the resistance mechanisms in tested S. aureus strains. Conferol, however, did not enhance the antibiotic efficacy mediated by inhibiting efflux pumps in bacteria.