SCREENING OF AN INHIBITOR OF THE TETRACYCLINE EFFLUX PUMP IN A TETRACYCLINE-RESISTANT CLINICAL-ISOLATE OF STAPHYLOCOCCUS-AUREUS-743

Clinically-isolated methicillin-resistant Staphylococcus aureus (MRSA) strain 743 exhibited resistance to tetracycline as judged from the ac tive efflux of the drug, The efflux of tetracycline was inhibited by a n uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and mino cycline, Inhibitors of the efflux pump were examined in this strain to determine the cellular accumulation of tetracycline, Out of seven com pounds examined, three caused a significant increase in the cellular c oncentration of tetracycline by inhibiting the efflux pump. Two of the m seem to be energy inhibitors. Ro 07-3149 inhibited the efflux pump w ithout affecting the energy state, and exhibited very low antibacteria l activity but showed weak synergy with tetracycline.