Plasmodium falciparum is a protozoan parasite and the causative agent of the most lethal form of malaria, a major disease in the tropical world. Chloroquine has been very effective in treatment of this disease, however the emergence of chloroquine-resistant strains in most geographical regions where malaria is endemic has made difficult the control of malaria. In addition, resistance to other antimalarials has been observed in these regions. The objective of this study was to determine the molecular mechanisms of multidrug resistance in P. falciparum. We have selected in vitro a P. falciparum strain resistant to actinomycin D from a parental drug sensitive clone, 3D7. Interestingly, we found that the actinomycin D resistant clone is less sensitive to chloroquine and mefloquine (antimalarial drugs) and rhodamine123. Comparison between parental 3D7 and resistant P. falciparum did not show differences in the copy number or level of expression of pfmdr1 previously implicated in chloroquine or mefloquine resistance. Furthermore, to identify if other P-glycoprotein homologues are involved in resistance, we used oligonucleotide primers to conserved sequences in ABC domains. An ABC protein, a homologue to the subunit 4, of the 26S proteasome complex has been cloned. To determine if this gene was involved in resistance to actinomycin D, a Northern blot was done. Surprisingly it was found a decreased in the expression of this gene in the resistant cell line, 3D7R/actD2, in comparison with its parental cell line, 3D7. Studies are in progress to determine the role of the PFS4 subunit in the resistance phenotype of 3D7R/actD2.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27504 |
| Date | January 1997 |
| Creators | Certad, Gabriela. |
| Contributors | Georges, Elias (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Institute of Parasitology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001618613, proquestno: MQ37102, Theses scanned by UMI/ProQuest. |
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