ArticleAntimicrobial agents and chemotherapy2016
Role of Plasmodium vivax Dihydropteroate Synthase Polymorphisms in Sulfa Drug Resistance.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 32 citations in OpenAlex.
- Molecular analysis of DHFR and DHPS gene mutations in Plasmodium cynomolgi from humans and macaques in Southeast Asia.Parasite (Paris, France) · 2025Article
- Limited Polymorphism in the Dihydrofolate Reductase (dhfr) and dihydropteroate synthase genes (dhps) of Plasmodium knowlesi isolate from Thailand.Acta tropica · 2023Article
- Malaria therapeutics: are we close enough?Parasites & vectors · 2023Review
- Crystal structure of Arabidopsis thaliana HPPK/DHPS, a bifunctional enzyme and target of the herbicide asulam.Plant communications · 2022Article
- Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China-Myanmar border during 2008‒2017.Infectious diseases of poverty · 2022Article
- Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly.JCI insight · 2021Article
- Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China-Myanmar border.Malaria journal · 2020Article
- The genomic architecture of antimalarial drug resistance.Briefings in functional genomics · 2019Review
- Plasmodium knowlesi as a model system for characterising Plasmodium vivax drug resistance candidate genes.PLoS neglected tropical diseases · 2019Article
- Structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase-dihydropteroate synthase fromThe Journal of biological chemistry · 2018Article
- The prevalence of molecular markers of drug resistance in Plasmodium vivax from the border regions of Thailand in 2008 and 2014.International journal for parasitology. Drugs and drug resistance · 2018Article
- Simultaneous detection of Plasmodium vivax dhfr, dhps, mdr1 and crt-o resistance-associated mutations in the Colombian Amazonian region.Malaria journal · 2018Article
- The Structural and Functional Basis for Recurring Sulfa Drug Resistance Mutations inFrontiers in microbiology · 2018Article
- [Research progress on genes mutations related to sulfa drug resistance inZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2017Review
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8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Dihydropteroate synthase (DHPS) is a known sulfa drug target in malaria treatment, existing as a bifunctional enzyme together with hydroxymethyldihydropterin pyrophosphokinase (HPPK). Polymorphisms in key residues of Plasmodium falciparum DHPS (PfDHPS) have been characterized and linked to sulfa drug resistance in malaria. Genetic sequencing of P. vivax dhps (Pvdhps) from clinical isolates has shown several polymorphisms at the positions equivalent to those in the Pfdhps genes conferring sulfa drug resistance, suggesting a mechanism for sulfa drug resistance in P. vivax similar to that seen in P. falciparum To characterize the role of polymorphisms in the PvDHPS in sulfa drug resistance, various mutants of recombinant PvHPPK-DHPS enzymes were expressed and characterized. Moreover, due to the lack of a continuous in vitro culture system for P. vivax parasites, a surrogate P. berghei model expressing Pvhppk-dhps genes was established to demonstrate the relationship between sequence polymorphisms and sulfa drug susceptibility and to test the activities of PvDHPS inhibitors on the transgenic parasites. Both enzyme activity and transgenic parasite growth were sensitive to sulfadoxine to different degrees, depending on the number of mutations that accumulated in DHPS. Ki values and 50% effective doses were higher for mutant PvDHPS enzymes than the wild-type enzymes. Altogether, the study provides the first evidence of sulfa drug resistance at the molecular level in P. vivax Furthermore, the enzyme inhibition assay and the in vivo screening system can be useful tools for screening new compounds for their activities against PvDHPS.
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