Rhodamine 123 efflux transporter in Haloferax volcanii is induced when cultured under 'metabolic stress' by amino acids: the efflux system resembles that in a doxorubicin-resistant mutant.
In this paper, we report that an archaebacterium, Haloferax volcanii, cultured in medium containing a large excess of amino acids showed very low levels of rhodamine 123 (RH123), which is a potent substrate for P-glycoprotein and the bacterial multidrug efflux transporter. This low level involved the active efflux of RH123 from the cells. The level of intracellular RH123 was increased and the efflux inhibited by the Ca2+-channel antagonist verapamil and also by various anti-cancer drugs. The efflux transporter was suggested to be ATP-driven. We have previously selected a mutant of H. volcanii with resistance to doxorubicin, by repeatedly culturing cells in 1.5 microM doxorubicin [Miyauchi, Komatsubara and Kamo (1992) Biochim. Biophys. Acta 1110, 144-150]. The acquisition of resistance to doxorubicin involves the active expulsion of lipophilic drugs such as RH123 and doxorubicin. It is notable that the drug spectrum and ATP-dependency of the amino acid-induced efflux transporter resemble those of the efflux transporter induced by doxorubicin.
Kaidoh
K
K
Laboratory of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido, Sapporo, Japan.
Miyauchi
S
S
Abe
A
A
Tanabu
S
S
Nara
T
T
Kamo
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology*; D003470:Culture Media; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006216:Halobacteriaceae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D008564:Membrane Potentials; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000596:Amino Acids; D003470:Culture Media; D012235:Rhodamines; D020112:Rhodamine 123; D004024:Dicyclohexylcarbodiimide; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D014700:Verapamil; D007930:Leucine