Drug extrusion in Corynebacterium glutamicum.
We selected a mutant of Corynebacterium glutamicum, EBR, which can grow in a medium containing cytotoxic ethidium bromide (EtBr) at a high concentration of 100 microM. The resistance to EtBr in the mutant was reversed by 2 microM reserpine, a potent inhibitor of mammalian p-glycoprotein and bacterial multidrug resistance (MDR) transporter, whereas reserpine alone had a minimal effect on cell growth. The mutant showed a much higher efflux rate of EtBr than wild-type cells, and the efflux was completely inhibited by 2 microM reserpine. In addition to reserpine, structurally unrelated chemicals such as quinidine, trifluorperazine, tetraphenylarsonium chloride, chlorpromazine and quinine inhibit the EtBr efflux, revealing that the putative efflux system(s) can recognize a variety of chemicals. The efflux activity was correlated with the membrane potential but not the intracellular ATP contents. We, therefore, concluded that the EtBr resistance may be involved by proton-motive-force driven multidrug efflux system(s).
Kaidoh
K
K
Laboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Kimura
M
M
Miyauchi
S
S
Nara
T
T
Kamo
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D003352:Corynebacterium / Q000235:genetics / Q000378:metabolism*; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple; D004996:Ethidium / Q000378:metabolism* / Q000494:pharmacology; D019450:Genes, MDR; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012110:Reserpine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D012110:Reserpine; D000255:Adenosine Triphosphate; D004996:Ethidium