Plasmodium falciparum:Mutation Pattern in the Dihydrofolate Reductase–Thymidylate Synthase Genes of Vietnamese Isolates, a Novel Mutation, and Coexistence of Two Clones in a Thai Patient
ZINDROU, S., DUNG, N. P., SY, N. D., SKÖLD, O., and SWEDBERG, G. 1996.Plasmodium falciparum:Mutation pattern in the dihydrofolate reductase–thymidylate synthase genes of Vietnamese isolates, a novel mutation, and coexistence of two clones in a Thai patient.Experimental Parasitology84,56–64. Pyrimeth...
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Published in | Experimental parasitology Vol. 84; no. 1; pp. 56 - 64 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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San Diego, CA
Elsevier Inc
01.10.1996
Elsevier |
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Abstract | ZINDROU, S., DUNG, N. P., SY, N. D., SKÖLD, O., and SWEDBERG, G. 1996.Plasmodium falciparum:Mutation pattern in the dihydrofolate reductase–thymidylate synthase genes of Vietnamese isolates, a novel mutation, and coexistence of two clones in a Thai patient.Experimental Parasitology84,56–64. Pyrimethamine and cycloguanil resistance ofPlasmodium falciparumhas been linked to mutations in the dihydrofolate reductase (dhfr) portion of thedhfr-tsgene. In this paper, the DNA sequence of thedhfr-tsgene of 50 isolates from Vietnam and 2 clones (T9/94 and T9/96) isolated from a malaria patient from Thailand have been analyzed. A comparison between these isolates and clones showed differential mutation patterns. Forty-eight isolates were found to consist of mutations associated with Pyrr. A novel leucine mutation at position 140 was found in the isolate VP8 and in clone T9/94. The isolate VP8 and the clone T9/94 were found to also have the characteristic changes at positions 16 (Val) and 108 (Thr) that have been found in cycloguanil-resistant isolates. The isolate VP35 was shown to be resistant to both antifolates, while the clone T9/96 was found to be sensitive to both antifolates and to have a sequence identical to that of wild-typedhfr-ts.The two clones from a single patient showed the coexistence of resistant and sensitive clones in the absence of treatment by antifolates. Since cycloguanil resistance seems to be rare in Vietnam, cycloguanil alone or in combination with other antimalarial agents might be an alternative for treatment and prophylaxis, even in areas with high resistance to pyrimethamine. |
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AbstractList | ZINDROU, S., DUNG, N. P., SY, N. D., SKÖLD, O., and SWEDBERG, G. 1996.Plasmodium falciparum:Mutation pattern in the dihydrofolate reductase–thymidylate synthase genes of Vietnamese isolates, a novel mutation, and coexistence of two clones in a Thai patient.Experimental Parasitology84,56–64. Pyrimethamine and cycloguanil resistance ofPlasmodium falciparumhas been linked to mutations in the dihydrofolate reductase (dhfr) portion of thedhfr-tsgene. In this paper, the DNA sequence of thedhfr-tsgene of 50 isolates from Vietnam and 2 clones (T9/94 and T9/96) isolated from a malaria patient from Thailand have been analyzed. A comparison between these isolates and clones showed differential mutation patterns. Forty-eight isolates were found to consist of mutations associated with Pyrr. A novel leucine mutation at position 140 was found in the isolate VP8 and in clone T9/94. The isolate VP8 and the clone T9/94 were found to also have the characteristic changes at positions 16 (Val) and 108 (Thr) that have been found in cycloguanil-resistant isolates. The isolate VP35 was shown to be resistant to both antifolates, while the clone T9/96 was found to be sensitive to both antifolates and to have a sequence identical to that of wild-typedhfr-ts.The two clones from a single patient showed the coexistence of resistant and sensitive clones in the absence of treatment by antifolates. Since cycloguanil resistance seems to be rare in Vietnam, cycloguanil alone or in combination with other antimalarial agents might be an alternative for treatment and prophylaxis, even in areas with high resistance to pyrimethamine. Pyrimethamine and cycloguanil resistance of Plasmodium falciparum has been linked to mutations in the dihydrofolate reductase (dhfr) portion of the dhfr-ts gene. In this paper, the DNA sequence of the dhfr-ts gene of 50 isolates from Vietnam and 2 clones (T9/94 and T9 /96) isolated from a malaria patient from Thailand have been analyzed. A comparison between these isolates and clones showed differential mutation patterns. Forty-eight isolates were found to consist of mutations associated with Pyr super(r). A novel leucine mutation at position 140 was found in the isolate VP8 and in clone T9/94. The isolate VP8 and the clone T9/94 were found to also have the characteristic changes at positions 16 (Val) and 108 (Thr) that have been found in cycloguanil-resistant isolates. The isolate VP35 was shown to be resistant to both antifolates, while the clone T9 /96 was found to be sensitive to both antifolates and to have a sequence identical to that of wild-type dhfr-ts. The two clones from a single patient showed the coexistence of resistant and sensitive clones in the absence of treatment by antifolates. Since cycloguanil resistance seems to be rare in Vietnam, cycloguanil alone or in combination with other antimalarial agents might be an alternative for treatment and prophylaxis, even in areas with high resistance to pyrimethamine. Pyrimethamine and cycloguanil resistance of Plasmodium falciparum has been linked to mutations in the dihydrofolate reductase (dhfr) portion of the dhfr-ts gene. In this paper, the DNA sequence of the dhfr-ts gene of 50 isolates from Vietnam and 2 clones (T9/94 and T9/96) isolated from a malaria patient from Thailand have been analyzed. A comparison between these isolates and clones showed differential mutation patterns. Forty-eight isolates were found to consist of mutations associated with Pyr. A novel leucine mutation at position 140 was found in the isolate VP8 and in clone T9/94. The isolate VP8 and the clone T9/94 were found to also have the characteristic changes at positions 16 (Val) and 108 (Thr) that have been found in cycloguanil-resistant isolates. The isolate VP35 was shown to be resistant to both antifolates, while the clone T9/96 was found to be sensitive to both antifolates and to have a sequence identical to that of wild-type dhfr-ts. The two clones from a single patient showed the coexistence of resistant and sensitive clones in the absence of treatment by antifolates. Since cycloguanil resistance seems to be rare in Vietnam, cycloguanil alone or in combination with other antimalarial agents might be an alternative for treatment and prophylaxis, even in areas with high resistance to pyrimethamine. |
Author | Zindrou, Sherwan Sy, Nguyen Duy Swedberg, Göte Sköld, Ola Dung, Nguyen Phuong |
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Keywords | Plasmodium falciparum Fansidar Sulfadoxine (a sulfonamide). DHFR, dihydrofolate reductase VP, Vietnamese patients TS, thymidylate synthase antifolates Cyc, cycloguanil Pyr, pyrimethamine Protozoa Antimalarial Enzyme Transferases Thymidylate synthase Resistance Antiprotozoal agent Methyltransferases Gene Parasiticid Isolate Oxidoreductases Dihydrofolate reductase Mutation Sporozoa |
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Snippet | ZINDROU, S., DUNG, N. P., SY, N. D., SKÖLD, O., and SWEDBERG, G. 1996.Plasmodium falciparum:Mutation pattern in the dihydrofolate reductase–thymidylate... Pyrimethamine and cycloguanil resistance of Plasmodium falciparum has been linked to mutations in the dihydrofolate reductase (dhfr) portion of the dhfr-ts... |
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SubjectTerms | Animals antifolates Antimalarials - pharmacology Base Sequence Biological and medical sciences Classical genetics, quantitative genetics, hybrids Cyc, cycloguanil DNA, Protozoan - analysis Drug Resistance - genetics Fansidar Folic Acid Antagonists - pharmacology Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Humans Malaria, Falciparum - parasitology Molecular Sequence Data Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - enzymology Plasmodium falciparum - genetics Point Mutation Proguanil Protozoa Pyr, pyrimethamine Pyrimethamine - pharmacology Sulfadoxine (a sulfonamide). DHFR, dihydrofolate reductase Tetrahydrofolate Dehydrogenase - genetics Thailand Thymidylate Synthase - genetics Triazines - pharmacology TS, thymidylate synthase Vietnam VP, Vietnamese patients |
Title | Plasmodium falciparum:Mutation Pattern in the Dihydrofolate Reductase–Thymidylate Synthase Genes of Vietnamese Isolates, a Novel Mutation, and Coexistence of Two Clones in a Thai Patient |
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