Publication: Pyrimethamine resistant mutations in Plasmodium falciparum
Issued Date
1992-01-01
Resource Type
ISSN
01666851
Other identifier(s)
2-s2.0-0026536286
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular and Biochemical Parasitology. Vol.52, No.2 (1992), 149-157
Suggested Citation
Sodsri Thaithong, Shiu Wan Chan, Supasorn Songsomboon, Prapon Wilairat, Nowarat Seesod, Tada Sueblinwong, Michael Goman, Robert Ridley, Geoffrey Beale Pyrimethamine resistant mutations in Plasmodium falciparum. Molecular and Biochemical Parasitology. Vol.52, No.2 (1992), 149-157. doi:10.1016/0166-6851(92)90047-N Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/22275
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Pyrimethamine resistant mutations in Plasmodium falciparum
Other Contributor(s)
Abstract
Three mutations in Plasmodium falciparum yielding increased resistance to pyrimethamine were obtained following treatment with chemical mutagens and selection in presence of pyrimethamine. From parasite clone TM4/8.2 a mutant, TM4/8.2/4.1, was produced which raised pyrimethamine resistance about 500 times and was found to involve an amino acid change in the DHFR-TS enzyme molecule from Ser108 to Asn108. A clone of another isolate, T9/94, yielded a mutant, T9/94/300.300, raising pyrimethamine resistance about 10 times and involving an amino acid change from Ile164 to Met164. However, another mutant from T9/94, T9/94/M1-1(b3), although it raised the pyrimethamine resistance 100 times, did not involve any changes in the coding sequence of the DHFR-TS gene, but resulted in the production of about twice as much DHFR-TS enzyme as the original clone T9/94. No amplification of the DHFR-TS gene was detected. It is concluded that changes in pyrimethamine resistance of malaria parasites may arise in at least 2 ways: (1) by structural changes in the DHFR domain of the DHFR-TS gene (as previously found by other workers); (2) by other changes, possibly affecting the expression of the DHFR-TS gene. The relative importance of these 2 mechanisms in causing resistance in wild populations of P. falciparum is discussed. © 1992.