Abstract
CHLOROQUINE is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function1–4. Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles5. The discovery that verapamil partially reverses chloroquine resistance in vitro6 led to the proposal that efflux may involve an ATP-driven P-glycoprotein pump similar to that in mammalian multidrug-resistant (mdr) tumor cell lines. Indeed, Plasmodium falciparum contains at least two mdr-like genes7,8, one of which has been suggested to confer the chloroquine resistant (CQR) phenotype7,9,10. To determine if either of these genes is linked to chloroquine resistance, we performed a genetic cross between CQR and chloroquine-susceptible (CQS) clones of P. falciparum. Examination of 16 independent recombinant progeny indicated that the rapid efflux phenotype is controlled by a single gene or a closely linked group of genes. But, there was no linkage between the rapid efflux, CQR phenotype and either of the mdr-like P. falciparum genes or amplification of those genes. These data indicate that the genetic locus governing chloroquine efflux and resistance is independent of the known mdr-like genes.
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References
Krogstad, D. J., Schlesinger, P. H. & Gluzman, I. Y. J. Cell Biol. 101, 2302–2309 (1985).
Yanon, A., Cabantchik, Z. I. & Ginsburg, H. EMBO J. 3, 2695–2700 (1984).
Yayon, A., Cabantchik, Z. I. & Ginsburg, H. Proc. natn. Acad. Sci. U.S.A. 82, 2784–2788 (1985).
Krogstad, D. J. & Schlesinger, P. H. N. Engl. J. Med. 317, 542–549 (1987).
Krogstad, D. J. et al. Science 238, 1283–1285 (1987).
Martin, S. K., Oduola, A. M. & Milhous, W. K. Science 235, 899–901 (1987).
Foote, S. J., Thompson, J. K., Cowman, A. F. & Kemp, D. J. Cell 57, 921–930 (1989).
Wilson, C. M. et al. Science 244, 1184–1186 (1989).
Higgins, C. Nature 340, 342–342 (1989).
Higgins, C. Nature 341, 103–103 (1989).
Bhasin, V. K. & Trager, W. Am. J. trop. Med. Hyg. 33, 534–537 (1984).
Oduola, A. M., Milhous, W. K., Weatherly, N. F., Bowdre, J. H. & Desjardins, R. E. Expl. Parasit. 67, 354–360 (1988).
Wellems, T. E. et al. Rev. Bras. Genet. 11, 813–825 (1988).
Walliker, D. et al. Science 236, 1661–1666 (1987).
Wellems, T. E. et al. Cell 49, 633–642 (1987).
Foote, S. J. et al. Nature, this issue.
Peterson, D. S., Walliker, D. & Wellems, T. E. Proc. natnl. Acad. Sci. U.S.A. 85, 9114–9118 (1988).
Cowman, A. F., Morry, M. J., Biggs, B. A., Cross, G. A. & Foote, S. J. Proc. natn. Acad. Sci. U.S.A. 85, 9109–9113 (1988).
Peterson, D. S., Milhous, W. K. & Wellems T.E. Proc. natn. Acad. Sci. U.S.A. 87, 3018–3022 (1990).
Foote, S. J., Galatis, D. & Cowman, A. F. Proc. natn. Acad. Sci. U.S.A. 87, 3014–3017 (1990).
Clyde, D. F. Med. Trop. Cooperaz. Sviluppo 3, 3–22 (1987).
Clyde, D. F. Med. Trop. Cooperaz. Sviluppo 3, 41–44 (1987).
Ifediba, T. & Vanderberg, J. P. Nature 294, 364–366 (1981).
Ponnudurai, T., Meuwissen, J. H., Leeuwenberg, A. D., Verhave, J. P. & Lensen, A. H. Trans. R. Soc. Trop. Med. Hyg. 76, 242–250 (1982).
Vanderberg, J. P. & Gwadz, R. W. in Malaria Vol. 2 (ed. Kreier, J. P.) 154–234 (Academic, New York, 1980).
Rosario, V. Science 212, 1037–1038 (1981).
Kilejian, A., Sharma, Y. D., Karoui, H. & Naslund, L. Proc. natn. Acad. Sci. U.S.A. 83, 7938–7941 (1986).
Pologe, L. G. & Ravetch, J. V. Nature 322, 474–477 (1986).
Reese, R. T., Langreth, S. G. & Trager, W. Bull. Wld Hlth Org. 57, 53–61 (1979).
Ravetch, J. V., Kochan, J. & Perkins, M. Science 227, 1593–1597 (1985).
Gros, P., Croop, J. & Housman, D. Cell 47, 371–380 (1986).
Weber, J. L. Gene 52, 103–109 (1987).
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Wellems, T., Panton, L., Gluzman, I. et al. Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross. Nature 345, 253–255 (1990). https://doi.org/10.1038/345253a0
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DOI: https://doi.org/10.1038/345253a0
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