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Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance.
The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of plasmodium falciparum-infected erythrocytes
Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil.
- D. Fidock, T. Wellems
- Biology, MedicineProceedings of the National Academy of Sciences…
- 30 September 1997
It is demonstrated that the only significant action of WR99210 is against parasite DHFR, and the transformation system described here has the advantage that P. falciparum drug-resistant lines are uniformly sensitive to methotrexate, which provides an approach for screening and identifying novel DHFR inhibitors that will be important in combined chemotherapeutic formulations against malaria.
Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine
- Juliana M. Sá, O. Twu, T. Wellems
- BiologyProceedings of the National Academy of Sciences
- 1 November 2009
Evidence for an emerging focus of AQ resistance in Tanzania and the persistence of 4-aminoquinoline-resistant parasites in South America suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations.
Dissecting the loci of low‐level quinine resistance in malaria parasites
Results identify additive QTL in segments of chromosomes (Chrs) 13, 7 and 5, and pairwise effects from two additional loci of Chrs 9 and 6 that interact, respectively, with the QTL of ChRS 13 and 7.
Malaria biology and disease pathogenesis: insights for new treatments
The current understanding of the biology of asexual blood-stage parasites and gametocytes and the ability to culture them in vitro lends optimism that high-throughput screenings of large chemical libraries will produce a new generation of antimalarial drugs.
A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum.
A genetic cross was used to construct such a map from 901 markers that fall into 14 inferred linkage groups corresponding to the 14 nuclear chromosomes, facilitating genome sequence assembly, localization of determinants for such traits as virulence and drug resistance, and genetic studies of parasite field populations.
Alternative mutations at position 76 of the vacuolar transmembrane protein PfCRT are associated with chloroquine resistance and unique stereospecific quinine and quinidine responses in Plasmodium…
It is concluded that the K76N or K76I change added to the other pre-existing mutations in the 106/1 PfCRT protein was responsible for CQR.
Transfection of Plasmodium falciparum within human red blood cells.
- Y. Wu, C. Sifri, H. Lei, X. Su, T. Wellems
- BiologyProceedings of the National Academy of Sciences…
- 14 February 1995
Transfected ring-stage P. falciparum parasites produced CAT signals at least as strong as transfected schizont-stage parasites even though ring stages are surrounded by more RBC cytoplasm than schizonts, advancing the ability to pursue genetic analysis of this major pathogen.
Genetic analysis of the human malaria parasite Plasmodium falciparum.
Novel forms of certain chromosomes, detected by pulsed-field gradient gel electrophoresis, were produced readily, showing that extensive rearrangements occur in the parasite genome after cross-fertilization.