Effect of galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana, as an inhibitor of efflux mechanism in resistant clinical isolates of Staphylococcus aureus

Abstract

Galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana roots, was investigated for its potentiating effect on the antimicrobial activity of antibiotics as well as ethidium bromide, in 6 multidrug resistance (MDR) clinical isolates of Staphylococcus aureus. Galbanic acid had inhibitory effect on none of the isolated bacteria tested (up to 800 µg /ml). The MIC range of ciprofloxacin, tetracycline and ethidium bromide, against all tested S. aureus were 10-80, 10-80 and 4-16 µg/ml, respectively. These were reduced to 2.5-5, 2.5-5 and 0.5-2 µg/ml in the presence of galbanic acid (300 µg /ml) or verapamil (100 µg /ml). The rate of ethidium bromide (2 µg /ml) accumulation in clinical isolates was enhanced with galbanic acid (300 µg /ml). There is also a decrease in loss of ethidium bromide from bacteria in the presence of galbanic acid. Similar results were obtained when verapamil (100 µg /ml) was used as an efflux pump inhibitor. Galbanic acid, like verapamil, a typical inhibitor of efflux pump, reduced the MIC of ethidium bromide and tested antibiotics. Since efflux is the only known reported mechanism for ethidium bromide resistance, the reduction in ethidium bromide MIC and enhanced accumulation as well as decreased efflux of ethidium bromide in the presence of galbanic acid, can be attributed to this efflux inhibitory properties.

Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?

“…Calcium antagonists improved in vitro activities of tetracycline and fluoroquinolones against S. aureus, Enterobacteriaceae and non-fermenters irrespective of whether the strains were tetracycline-or fluoroquinolone-resistant [158][159][160]. It also improved activities of ofloxacin, rifampicin, and bedaquilin, but not isoniazid or amikacin against M. tuberculosis as well as M. abscessus (Table 3) [ [161][162][163][164][165][166][167][168][169]. Verapamil also increased the intraphagocytic activities of isoniazid and rifampicin [168] as well as bedaquilin and moxifloxacin [168] against drug-susceptible and drug-resistant M. tuberculosis and also the intracellular activity of azithromycin against L. monocytogenes [170,171] and that of daptomycin against S. aureus [172].…”

Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition

“…Many scientists have investigated the influence of P-gp inhibitors from natural sources (vasicine acetate, canthin-6-one, ergotamine, berberine, harmaline, reserpine, theobromine, chelerythrine, isorhamnetin, aegicerin, galbanic acid, orizabin, porphyrin, etc.) on the antimicrobial activity of antimicrobial agents that can increase their accumulation inside the cells and increase the antimicrobial action [ 61 , 62 , 69 , 72 , 94 , 121 , 124 , 174 , 186 , 224 , 232 , 236 , 258 ].…”

Review on plant antimicrobials: a mechanistic viewpoint

“…Coumarins are capable of binding to isoprene units in plant cells to form more complex structures. 6-Geranyl coumarin (50) and gallbanic acid (51) are two terpenoid coumarins that inhibited EP in S. aureus , significantly [170, 171]. Up to 8-fold reduction in the MIC of ciprofloxacin was observed for galbanic acid, and its mode of action and potency were comparable to verapamil as a well-known inhibitor of EP.…”