Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea

Details

Serval ID
serval:BIB_52F407C771C6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea
Journal
American Journal of Tropical Medicine and Hygiène
Author(s)
Reeder  J. C., Rieckmann  K. H., Genton  B., Lorry  K., Wines  B., Cowman  A. F.
ISSN
0002-9637 (Print)
Publication state
Published
Issued date
08/1996
Volume
55
Number
2
Pages
209-13
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Abstract
Plasmodium falciparum isolates from 24 Papua New Guinean patients with symptomatic malaria were tested for susceptibility to pyrimethamine and cycloguanil. Thirteen isolates were sensitive to both agents and the remainder exhibited varying degrees of resistance. No isolates were found to be resistant to one agent yet sensitive to the other and a positive correlation suggesting cross-resistance was found. Parasite DNA extracted from the patients' stained blood slides was amplified and sequenced to examine point mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase genes (DHPS) associated with antifolate resistance. All resistant isolates possessed mutations in the DHFR gene at codon 108, the majority changing from Ser to Asn, but one isolate from Ser to Thr, a change not previously reported in field isolates. A second mutation of the DHFR gene at Cys-59 to Arg was present in isolates with higher level resistance, but not exclusively so. Sequencing the DHPS gene, as a predictor of sulfadoxine resistance, revealed only one example that was different from DHPS alleles of sensitive isolates.
Keywords
Animals Antimalarials/*pharmacology Base Sequence DNA Primers/chemistry Dihydropteroate Synthase/*genetics Drug Resistance/genetics Folic Acid Antagonists/*pharmacology Humans Malaria, Falciparum/parasitology Molecular Sequence Data Plasmodium falciparum/*drug effects/enzymology/*genetics *Point Mutation Polymerase Chain Reaction Pyrimethamine/pharmacology Sequence Analysis, DNA Tetrahydrofolate Dehydrogenase/*genetics Triazines/pharmacology
Pubmed
Web of science
Create date
28/01/2008 11:48
Last modification date
20/08/2019 14:08
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