The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum
Open accessAbstract
Plasmodium falciparum causes the most severe form of malaria in humans. An important class of drugs in malaria treatment is the sulfone/sulfonamide group, of which sulfadoxine is the most commonly used. The target of sulfadoxine is the enzyme dihydropteroate synthase (DHPS), and sequencing of the DHPS gene has identified amino acid differences that may be involved in the mechanism of resistance to this drug. In this study we have sequenced the DHPS gene in 10 isolates from Thailand and identified a new allele of DHPS that has a previously unidentified amino acid difference. We have expressed eight alleles of P. falciparum PPPK-DHPS in Escherichia coli and purified the functional enzymes to homogeneity. Strikingly, the K i for sulfadoxine varies by almost three orders of magnitude from 0.14 μM for the DHPS allele from sensitive isolates to 112 μM for an enzyme expressed in a highly resistant isolate. Comparison of the K i of different sulfonamides and the sulfone dapsone has suggested that the amino acid differences in DHPS would confer cross-resistance to these compounds. These results show that the amino acid differences in the DHPS enzyme of sulfadoxine-resistant isolates of P. falciparum are central to the mechanism of resistance to sulfones and sulfonamides.
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Mechanisms of Resistance of Malaria Parasites to Antifolates
Gregson, A., & Plowe, C. V. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.4 · Cited by 499
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Metadata
- Authors
- Triglia, T., Menting, J. G. T., Wilson, C., & Cowman, A. F.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-12-09
- Volume
- 94
- Issue
- 25
- Pages
- 13944-13949
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2079127050
- Cited by
- 422
- References
- 23
- FWCI
- 17.12
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. https://app.cochat.ai/papers/10.1073/pnas.94.25.13944
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- Triglia, T., Menting, J. G. T., Wilson, C., & Cowman, A. F. (1997). Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.25.13944
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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