Fitness effects of DHFR-TS mutations associated with pyrimethamine resistance in apicomplexan parasites

Molecular Microbiology

Volumn 50, Issue 4, 2003, Pages 1319-1327

  Fohl, Leah M ^a   Roos, David S ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; ASPARAGINE; DIHYDROFOLATE REDUCTASE THYMIDYLATE SYNTHASE; PROTOZOAL PROTEIN; PYRIMETHAMINE; UNCLASSIFIED DRUG;

ADAPTATION; ALLELE; APICOMPLEXA; ARTICLE; CONTROLLED STUDY; GENE MUTATION; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; NUCLEOTIDE SEQUENCE; PARASITE; PLASMODIUM FALCIPARUM; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; TISSUE CULTURE; TOXOPLASMA GONDII;

ANIMALS; CELL LINE; DRUG RESISTANCE; FOLIC ACID ANTAGONISTS; HUMANS; MICE; MULTIENZYME COMPLEXES; MUTATION; PHENOTYPE; PLASMODIUM FALCIPARUM; POLYMERASE CHAIN REACTION; POLYMORPHISM, GENETIC; PYRIMETHAMINE; SELECTION (GENETICS); TETRAHYDROFOLATE DEHYDROGENASE; THYMIDYLATE SYNTHASE; TOXOPLASMA;

APICOMPLEXA; PLASMODIUM FALCIPARUM; PROTOZOA; TOXOPLASMA GONDII;

EID: 0344826569     PISSN: 0950382X     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2958.2003.03756.x     Document Type: Article

References (41)

1. Bjorkman, J., Nagaev, I., Berg, O.G., Hughes, D., and Andersson, D.I. (2000) Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance. Science 287: 1479-1482.
2. Black, M.W., and Boothroyd, J.C. (2000) Lytic cycle of Toxoplasma gondii. Microbiol Mol Biol Rev 64: 607-623.
3. Boothroyd, J.C., Kim, K., Sibley, D., and Soldati, D. (1995) Toxoplasma as a paradigm for the use of genetics in the study of protozoan parasites. In Molecular Approaches to Parasitiology, Vol. 12. Boothroyd, J.C., and Komuniecki, R. (eds). New York: John Wiley and Sons, Inc., pp. 211-225.
4. Bryce, J., Roungou, J.B., Nguyen-Dinh, P., Naimoli, J.F., and Breman, J.G. (1994) Evaluation of national malaria control programmes in Africa. Bull World Health Organ 72: 371-381.
5. Bwijo, B., Kaneko, A., Takechi, M., Zungu, I.L., Moriyama, Y., Lum, J.K., et al. (2003) High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi. Acta Trop 85: 363-373.
6. Cowman, A.F. (1988) Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. Proc Natl Acad Sci USA 85: 9109-9113.
7. Donald, R.G.K., and Roos, D.S. (1993) Stable molecular transformation of Toxoplasma gondii: a selectable dihydrofolate reductase-thymidylate synthase marker based on drug-resistance mutations in malaria. Proc Natl Acad Sci USA 90: 11703-11707.
8. Donald, R.G.K., and Roos, D.S. (1994) Homologous recombination and gene replacement at the dihydrofolate reductase-thymidylate synthase locus in Toxoplasma gondii. Mol Biochem Parasitol 63: 243-253.
9. Donald, R.G., and Roos, D.S. (1998) Gene knock-outs and allelic replacements in Toxoplasma gondii: HXGPRT as a selectable marker for hit-and-run mutagenesis. Mol Biochem Parasitol 91: 295-305.
10. Doumbo, O.K., Kayentao, K., Djimde, A., Cortese, J.F., Diourte, Y., Konare, A., et al. (2000) Rapid selection of Plasmodium falciparum dihydrofolate reductase mutants by pyrimethamine prophylaxis. J Infect Dis 182: 993-996.
11. Dubey, J.P. (1998) Advances in the life cycle of Toxoplasma gondii. Int J Parasitol 28: 1019-1024.
12. Fichera, M.E., Bhopale, M.K., and Roos, D.S. (1995) In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii. Antimicrob Agents Chemother 39: 1530-1537.
13. Frenkel, J.K., and Ambroise-Thomas, P. (1997) Genomic drift of Toxoplasma gondii. Parasitol Res 83: 1-5.
14. Greenwood, B., and Mutabingwa, T. (2002) Malaria in 2002. Nature 415: 670-672.
15. Jones, A.S. (1958) Mass treatment with pyrimethamine. A study of resistance and cross resistance resulting from a field trial in hyperendemic malarous area of Makueni, Kenya, September 1952-September 1953. Trans R Soc Trop Med Hyg 52: 547-561.
16. Liang, P.H., and Anderson, K.S. (1998) Substrate channeling and domain-domain interactions in bifunctional thymidylate synthase-dihydrofolate reductase. Biochemistry 37: 12195-12205.
17. Mberu, E.X., Nzila, A.M., Nduati, E., Ross, A., Monks, S.M., Kokwaro, G.O., Watkins, W.M., and Hopkins Sibley, C. (2002) Plasmodium falciparum: in vitro activity of sulfadoxine and dapsone in field isolates from Kenya: point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance. Exp Parasitol 101: 90-96.
18. Nagaev, I., Bjorkman, J., Andersson, D.I., and Hughes, D. (2001) Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus. Mol Microbiol 40: 433-439.
19. Nzila, A.M., Mberu, E.K., Sulo, J., Dayo, H., Winstanley, P.A., Sibley, C.H., and Watkins, W.M. (2000) Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother 44: 991-996.
20. Omar, S.A., Adagu, I.S., and Warhurst, D.C. (2001) Can pretreatment screening for dhps and dhfr point mutations in Plasmodium falciparum infections be used to predict sulfadoxine-pyrimethamine treatment failure? Trans R Soc Trop Med Hyg 95: 315-319.
21. Peterson, D.S., Walliker, D., and Wellems, T.E. (1988) Evidence that a point mutation in dihydrofolate reductase-thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA 85: 9114-9118.
22. Plowe, C.V., and Wellems, T.E. (1995) Molecular approaches to the spreading problem of drug resistant malaria. Adv Exp Med Biol 390: 197-209.
23. Reynolds, M.G., and Roos, D.S. (1998) A biochemical and genetic model for parasite resistance to antifolates. Toxoplasma gondii provides insights into pyrimethamine and cycloguanil resistance in Plasmodium falciparum. J Biol Chem 273: 3461-3469.
24. Ridley, R.G. (1998) Malaria: dissecting chloroquine resistance. Curr Biol 8: R346-R349.
25. Ridley, R.G. (2002) Medical need, scientific opportunity and the drive for antimalarial drugs. Nature 415: 686-693.
26. Roos, D.S. (1993) Primary structure of the dihydrofolate reductase-thymidylate synthase gene from Toxoplasma gondii. J Biol Chem 268: 6269-6280.
27. Roos, D.S. (1996) Molecular genetic tools for the identification and analysis of drug targets in Toxoplasma gondii. Curr Top Microbiol Immunol 219: 247-259.
28. Roos, D.S., Donald, R.G.K., Morrissette, N.S., and Moulton, A.L.C. (1994) Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii. Methods Cell Biol 45: 27-63.
29. Roos, D.S., Crawford, M.J., Donald, R.G., Fohl, L.M., Hager, K.M., Kissinger, J.C., et al. (1999) Transport and trafficking: Toxoplasma as a model for Plasmodium. Novartis Found Symp 226: 176-195; (discussion) 195-178.
30. Roos, D.S., Darling, J.A., Reynolds, M.G., Hager, K.M., Striepen, B., and Kissinger, J.C. (2000) Toxoplasma as a model parasite: Apicomplexan biochemistry, cell biology, molecular genetics, genomics . . . and beyond. In Biology of Parasitism. Pearce, C.T.E.J. (ed.). Boston: Kluwer, pp. 143-167.
31. Shiff, C. (2002) Integrated approach to malaria control. Clin Microbiol Rev 15: 278-293.
32. Sibley, C.H., Hyde, J.E., Sims, P.F., Plowe, C.V., Kublin, J.G., Mberu, E.K., et al. (2001) Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 17: 582-588.
33. Sirawaraporn, W. (1998) Dihydrofolate reductase and antifolate resistance in malaria. Drug Resist Updat 1: 397-406.
34. Sirawaraporn, W., Sathitkul, T., Sirawaraporn, R., Yuthavong, Y., and Santi, D.V. (1997) Antifolate-resistant mutants of Plasmodium falciparum dihydrofolate reductase. Proc Natl Acad Sci USA 94: 1124-1129.
35. Sirawaraporn, W., Sirawaraporn, R., Yongkiettrakul, S., Anuwatwora, A., Rastelli, G., Kamchonwongpaisan, S., and Yuthavong, Y. (2002) Mutational analysis of Plasmodium falciparum dihydrofolate reductase: the role of aspartate 54 and phenylalanine 223 on catalytic activity and antifolate binding. Mol Biochem Parasitol 121: 185-193.
36. Striepen, B., White, M.W., Li, C., Guerini, M.N., Malik, S.B., Logsdon, J.M., Jr, et al. (2002) Genetic complementation in apicomplexan parasites. Proc Natl Acad Sci USA 99: 6304-6309.
37. Tanaka, M., Gu, H.M., Bzik, D.J., Li, W.B., and Inselburg, J.W. (1990) Dihydrofolate reductase mutations and chromosomal changes associated with pyrimethamine resistance of Plasmodium falciparum. Mol Biochem Parasitol 39: 127-134.
38. Triglia, T., Wang, P., Sims, P.F., Hyde, J.E., and Cowman, A.F. (1998) Allelic exchange at the endogenous genomic locus in Plasmodium falciparum proves the role of dihydropteroate synthase in sulfadoxine-resistant malaria. EMBO J 17: 3807-3815.
39. Trujillo, M., Donald, R.G.K., Roos, D.S., Greene, P.J., and Santi, D.V. (1996) Heterologous expression and characterization of the bifunctional dihydrofolate reductase-thymidylate synthase enzyme of Toxoplasma gondii. Biochemistry 35: 6366-6374.
40. Wang, P., Lee, C.S., Bayoumi, R., Djimde, A., Doumbo, O., Swedberg, G., et al. (1997) Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. Molbiochem Parasitol 89: 161-177.
41. Wellems, T.E., and Plowe, C.V. (2001) Chloroquine-resistant malaria. J Infect Dis 184: 770-776.