DRUG EXTRUSION IN CORYNEBACTERIUM-GLUTAMICUM

We selected a mutant of Corynebacterium glutamicum, EBR, which can gro w in a medium containing cytotoxic ethidium bromide (EtBr) at a high c oncentration of 100 mu M. The resistance to EtBr in the mutant was rev ersed by 2 mu M reserpine, a potent inhibitor of mammalian p-glycoprot ein and bacterial multidrug resistance (MDR) transporter, whereas rese rpine alone had a minimal effect on cell growth, The mutant showed a m uch higher efflux rate of EtBr than mild-type cells, and the efflux wa s completely inhibited by 2 mu M reserpine, In addition to reserpine, structurally unrelated chemicals such as quinidine, trifluorperazine, tetraphenylarsonium chloride, chlorpromazine and quinine inhibit the E tBr efflux, revealing that the putative efflux system(s) can recognize a variety of chemicals. The efflux activity was correlated with the m embrane potential but not the intracellular ATP contents. We, therefor e, concluded that the EtBr resistance may be involved by proton-motive -force driven multidrug efflux system(s).