Monday, July 27, 2009
P122

EFFECT OF GALBANIC ACID, A SESQUITERPENE COUMARIN FROM FERULA SZOWITSIANA, AS A PUTATIVE MULTIDRUG RESISTANCE INHIBITOR ON CLINICAL ISOLATES OF STAPHYLOCOCCUS

Bibi Sedigheh Fazly Bazzaz, Zahra Memariani, Zahra Khashaiar manesh, and Mehrdad Iranshahi. Pharmaceutical Microbiology, School of Pharmacy & Biotechnology Research Center, Mashhad University of Medical Sciences, Vakilabad Blvd., Mashhad, Iran

The aim of this study was to demonstrate the effect of galbanic acid (GA), a sesquiterpene coumarin from Ferula szowitsiana roots, on potentiating antibiotic activity by inhibiting efflux pumps in multidrug resistant (MDR) clinical isolates of Staphylococcus aureus.The MICs of ciprofloxacin (CP), ethidium bromide (EtBr) alone or in combination with GA or verapamil (an efflux pump inhibitor), on 6 MDR clinical isolates of S. aureus were determined using micro-titer plate method. In fluorescence assays, the increase and decrease in the fluorescence intensity as a sign of either accumulation or loss of EtBr (2 mg/ml) respectively (S. aureus ATCC 6538, or resistant clinical isolates), were continuously monitored over the time (λ ex: 530 nm, λ em: 600 nm). This was repeated for EtBr in the presence of either GA (200 mg/ml) or verapamil (100 mg/ml).GA had no inhibitory effect on all tested bacteria (up to 800 mg/ml). The MICs of CP and EtBr, against S. aureus were 10-80 and 4-16 mg/ml respectively. These were reduced to less than 1.25 and 0.5 mg/ml in the presence of GA or verapamil. The rate of EtBr accumulation in isolates was enhanced with GA. A decrease in loss of EtBr from bacteria was observed in the presence of GA. Similar results were obtained with verapamil. Since efflux is the only known reported mechanism for EtBr resistance, the enhanced accumulation and decreased efflux of EtBr in the presence of GA, may attribute to its role as an efflux pump inhibitor.

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