Abstract
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.
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Selected References
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- Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lanyi J. K., MacDonald R. E. Existence of electrogenic hydrogen ion/sodium ion antiport in Halobacterium halobium cell envelope vesicles. Biochemistry. 1976 Oct 19;15(21):4608–4614. doi: 10.1021/bi00666a010. [DOI] [PubMed] [Google Scholar]
- Miyauchi S., Komatsubara M., Kamo N. In archaebacteria, there is a doxorubicin efflux pump similar to mammalian P-glycoprotein. Biochim Biophys Acta. 1992 Oct 5;1110(2):144–150. doi: 10.1016/0005-2736(92)90351-l. [DOI] [PubMed] [Google Scholar]
- Tawara E., Kamo N. Glucose transport of Haloferax volcanii requires the Na(+)-electrochemical potential gradient and inhibitors for the mammalian glucose transporter inhibit the transport. Biochim Biophys Acta. 1991 Dec 9;1070(2):293–299. doi: 10.1016/0005-2736(91)90069-k. [DOI] [PubMed] [Google Scholar]