Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-27T06:47:01.310Z Has data issue: false hasContentIssue false
  • English
  • Français

Transcripts of the multidrug resistance genes in chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

Published online by Cambridge University Press:  06 April 2009

R. M. Ekong ,
K. J. H. Robson ,
D. A. Baker  and
D. C. Warhurst
R. M. Ekong
Affiliation:
Medical Parasitology Department, London School of Hygiene and Tropical Medicine, Keppel Street, London WCIE 7HT
K. J. H. Robson
Affiliation:
MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU
D. A. Baker
Affiliation:
Medical Parasitology Department, London School of Hygiene and Tropical Medicine, Keppel Street, London WCIE 7HT
D. C. Warhurst
Affiliation:
Medical Parasitology Department, London School of Hygiene and Tropical Medicine, Keppel Street, London WCIE 7HT
Get access Rights & Permissions [Opens in a new window]

Summary

Homologues of the mammalian multidrug resistance gene have been identified in isolates and clones of Plasmodium falciparum and designated pfmdr1 and pfmdr2. Mutations in pfmdr1 have been associated with chloroquine resistance but confirmation could not be obtained in a genetic cross. We have examined the copy number and expression of pfmdr1 and pfmdr2 in chloroquine-sensitive and -resistant P. falciparum and have found no relationship between the copy number of either gene and chloroquine resistance. However, a marked correlation was seen between levels of mRNA transcribed for each gene and chloroquine resistance. Two transcripts of pfmdr1 were detected, and in the asexual blood cycle an 8 kb transcript appeared first, followed by the appearance of a 7 kb species.

Keywords

Plasmodium falciparumchloroquine resistancepfmdr transcripts
Type
Research Article
Information
Parasitology , Volume 106 , Issue 2 , February 1993 , pp. 107 - 115
Copyright
Copyright © Cambridge University Press 1993

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Balzi, E., Chen, W., Ulaszewski, S., Capieaux, E., & Goffeau, A., (1987). The multidrug resistance gene PDR1 from Saccharomyces cerevisiae. Journal of Biological Chemistry 262, 16871–9.CrossRefGoogle ScholarPubMed
Bhasin, V. K. & Tracer, W. (1984). Gametocyte-forming and non-gametocyte-forming clones of Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 33, 534–7.CrossRefGoogle ScholarPubMed
Bitonti, A. J., Sjoerdsma, A., McCann, P. P., Kyle, D. E., Oduola, A. M. J., Rossan, R. N., Milhous, W. K. & Davidson, D. E. Jr. (1988). Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine. Science 242, 1301–3.CrossRefGoogle ScholarPubMed
Chen, C.-J., Chin, J. E., Ueda, K., Clark, D. P., Pastan, I, Gottesman, M. M. & Roninson, I. B. (1986). Internal duplication and homology with bacterial transport proteins in themdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47, 381–9.CrossRefGoogle ScholarPubMed
Chen, P., Lamont, G., Elliott, T., Kidson, C., Brown, G., Mitchell, G., Stage, J. & Alpers, M. (1980). Plasmodium falciparum strains from Papua New Guinea: culture characteristics and drug sensitivity. Southeast Asian Journal of Tropical Medicine and Public Health 11, 435–40.Google ScholarPubMed
Cheung, A., Shaw, A. R., Leban, J. & Perrin, L. H. (1985). Cloning and expression in Escherichia coli of a surface antigen of Plasmodium falciparum merozoites. EMBO Journal 4, 1007–12.CrossRefGoogle ScholarPubMed
Cowman, A. F., Karcz, S., Galatis, D, & Culvenor, J. G. (1991). A P-glycoprotein homologue of Plasmodium falciparum is localised on the digestive vacuole. Journal of Cell Biology 113, 1033–42.CrossRefGoogle ScholarPubMed
Dame, J. B., Williams, J. L., McCutchan, T. F., Weber, J. L., Wirtz, R. A., Hockmeyer, W. T., Maloy, W. L., Haynes, J. D., Schneider, I., Roberts, D., Sanders, G. S., Reddy, E. P., Diggs, C. L. & Miller, L. H. (1984). Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science 225, 593–9.CrossRefGoogle ScholarPubMed
Desjardins, R. E., Canfield, C. J., Haynes, J. D. & Chulay, J. D. (1979). Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrobial Agents and Chemotherapy 16, 710–18.CrossRefGoogle ScholarPubMed
Edman, U., Meza, I. & Agabian, N. (1987). Genomic and cDNA sequences from a virulent strain of Entamoeba histolytica. Proceedings of the National Academy of Sciences, USA 84, 3024–8.CrossRefGoogle ScholarPubMed
Fairlamb, A. H., Warhurst, D. C. & Peters, W. (1985). An improved technique for the cultivation of Plasmodium falciparum in vitro without daily medium change. Annals of Tropical Medicine and Parasitology 79, 379–84.CrossRefGoogle ScholarPubMed
Feinburg, A. P. & Vogelstein, B. (1983). A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Analytical Biochemistry 132, 6–13.CrossRefGoogle Scholar
Fojo, A., Akiyama, S., Gottesman, M. M. & Pastan, I. (1985). Reduced drug accumulation in multiply drug-resistant human carcinoma cell lines. Cancer Research 45, 3002–7.Google Scholar
Fojo, A. T., Ueda, K., Slamon, D. J., Poplack, D. G., Gottesman, M. M. & Pastan, I. (1987). Expression of a multidrug resistance gene in human tumours and tissues. Proceedings of the National Academy of Sciences USA 84, 265–9.CrossRefGoogle ScholarPubMed
Foote, S. J., Kyle, D. E., Martin, S. K., Oduola, A. M. J., Forsyth, K., Kemp, D. J. & Cowman, A. F. (1990). Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. Nature, London 345, 255–8.CrossRefGoogle ScholarPubMed
Foote, S. J., Thompson, J. K., Cowman, A. F. & Kemp, D. J. (1989). Amplification of the multidrug resistance gene in some chloroquine-resistant isolates of P. falciparum. Cell 57, 921–30.CrossRefGoogle ScholarPubMed
Gerlach, J. H., Endicott, J. A., Juranka, P. F., Henderson, G., Sarangi, F., Deuchars, K. L. & Ling, V. (1986). Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature, London 324, 485–9.CrossRefGoogle Scholar
Gilson, L., Mahanty, H. K. & Kolter, R. (1990). Genetic analysis of an MDR-like export system: the secretion of colicin V. EMBO Journal 9, 3875–84.CrossRefGoogle ScholarPubMed
Hall, R., Hyde, J. E., Goman, M., Simmons, D. L., Hope, I. A., Mackay, M. & Scaife, J. (1984). Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. Nature, London 311, 379–82.CrossRefGoogle ScholarPubMed
Horton, R. J. (1988). Introduction of halofantrine for malaria treatment. Parasitology Today 4, 238–9.CrossRefGoogle ScholarPubMed
Krogstad, D. J., Gluzman, I. Y., Kyle, D. E., Oduola, A. M., Martin, S. K., Milhous, W. K. & Schlesinger, P. H. (1987). Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance. Science 238, 1283–5.CrossRefGoogle ScholarPubMed
Kuchler, K., Sterne, R. E. & Thorner, J. (1989). Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells. EMBO Journal 8, 3973–84.CrossRefGoogle ScholarPubMed
McGrath, J. P. & Varshavsky, A. (1989). The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein. Nature, London 340, 400–4.CrossRefGoogle ScholarPubMed
Martin, S. K., Oduola, A. M. J. & Milhous, W. K. (1987). Reversal of chloroquine resistance in Plasmodium falciparum by verapamil. Science 235, 899–901.CrossRefGoogle ScholarPubMed
Nguyen-Dinh, P. & Payne, D. (1980). Pyrimethamine sensitivity in Plasmodium falciparum: determination in vitro by a modified 48-hour test. Bulletin of the World Health Organization 58, 909–12.Google ScholarPubMed
O'Neill, M. J., Bray, D. H., Boardman, P., Phillipson, J. D. & Warhurst, D. C. (1985). Plants as sources of antimalarial drugs. Part 1. In vitro test method for the evaluation of crude extracts from plants. Planta Medica 5, 394–8.CrossRefGoogle Scholar
Peters, W., Ekong, R., Robinson, B. L., Warhurst, D. C. & Pan, X.-Q. (1989). Antihistaminic drugs that reverse chloroquine resistance in Plasmodium falciparum. Lancet 2, 334–5.CrossRefGoogle ScholarPubMed
Robson, K. J. H., Hall, J. R. S., Jennings, M. W., Harris, T. J. R., Marsh, K., Newbold, C. I., Tate, V. E. & Weatherall, D. J. (1988). A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature, London 335, 79–82.CrossRefGoogle ScholarPubMed
Robson, K. J. H. & Jennings, M. W. (1991). The Structure of the calmodulin gene of Plasmodium falciparum. Molecular and Biochemical Parasitology 46, 19–34.CrossRefGoogle ScholarPubMed
Sanderson, A., Walliker, D. & Molez, J.-F. (1981). Enzyme typing of Plasmodium falciparum from African and some other old world countries. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 263–7.CrossRefGoogle ScholarPubMed
Tanabe, K., Kato, M., Izumo, A., Hagiwara, A. & Doi, S. (1990). Plasmodium chabaudi: in vivo effects of Ca2+ antagonists on chloroquine-resistant and chloroquine-sensitive parasites. Experimental Parasitology 70, 419–26.CrossRefGoogle ScholarPubMed
Thaithong, S. & Beale, G. H. (1981). Resistance of ten Thai isolates of Plasmodium falciparum to chloroquine and pyrimethamine by in vitro tests. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 271–3.CrossRefGoogle ScholarPubMed
Thaithong, S., Beale, G. H., Fenton, B., McBride, J., Rosario, V., Walker, A. & Walliker, D. (1984). Clonal diversity in a single isolate of the malaria parasite Plasmodium falciparum. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 242–5.CrossRefGoogle Scholar
Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M. M., Pastan, I. & Willingham, M. C. (1987). Cellular localisation of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proceedings of the National Academy of Sciences, USA 84, 7735–8.CrossRefGoogle ScholarPubMed
Tracer, W. & Jensen, J. B. (1976). Human malaria parasites in continuous culture. Science 193, 673–5.Google Scholar
Tsuruo, T., Iida, H., Tsukagoshi, S. & Sakurai, Y. (1981). Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Research 41, 1967–72.Google ScholarPubMed
Vernes, A., Haynes, J. D., Tapchaisri, P., Williams, J. L., Dutoit, E. & Diggs, C. L. (1984). Plasmodium falciparum strain-specific human antibody inhibits merozoite invasion of erythrocytes. American Journal of Tropical Medicine and Hygiene 33, 197–203.CrossRefGoogle ScholarPubMed
Wellems, T. E., Panton, L. J., Gluzman, I. Y., Do Rosario, V. E., Gwadz, R. W., Walker-Jonah, A. & Krogstad, D. J. (1990). Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross. Nature, London 345, 253–5.CrossRefGoogle ScholarPubMed
Wellems, T. E., Walker-Jonah, A. & Panton, L. J. (1991). Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7. Proceedings of the National Academy of Sciences, USA 88, 3382–6.CrossRefGoogle ScholarPubMed
Wesseling, J. G., De Ree, J. M., Ponnudurai, T., Smits, M. A. & Schoenmakers, J. G. G.(1988). Nucleotide sequence and deduced amino acid sequence of a Plasmodium falciparum actin gene. Molecular and Biochemical Parasitology 27, 313–20.CrossRefGoogle ScholarPubMed
Wilson, C. M., Serrano, A. E., Wasley, A., Bogenschutz, M. P., Shankar, A. H. & Wirth, D. F. (1989). Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum. Science 244, 1184–6.CrossRefGoogle ScholarPubMed
Ye, Z. & van Dyke, K. (1988). Reversal of chloroquine resistance in falciparum malaria independent of calcium channels. Biochemical and Biophysical Research Communications 155, 476–81.Google ScholarPubMed