The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine
Open accessAbstract
The widely used antimalarial combination therapy dihydroartemisinin + piperaquine (DHA + PPQ) has failed in Cambodia. Here, we perform a genomic analysis that reveals a rapid increase in the prevalence of novel mutations in the Plasmodium falciparum chloroquine resistance transporter PfCRT following DHA + PPQ implementation. These mutations occur in parasites harboring the K13 C580Y artemisinin resistance marker. By introducing PfCRT mutations into sensitive Dd2 parasites or removing them from resistant Cambodian isolates, we show that the H97Y, F145I, M343L, or G353V mutations each confer resistance to PPQ, albeit with fitness costs for all but M343L. These mutations sensitize Dd2 parasites to chloroquine, amodiaquine, and quinine. In Dd2 parasites, multicopy plasmepsin 2, a candidate molecular marker, is not necessary for PPQ resistance. Distended digestive vacuoles were observed in pfcrt-edited Dd2 parasites but not in Cambodian isolates. Our findings provide compelling evidence that emerging mutations in PfCRT can serve as a molecular marker and mediator of PPQ resistance.
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Spread of Artemisinin Resistance in Plasmodium falciparum Malaria
Ashley, E. A., Dhorda, M., Fairhurst, R. M., Amaratunga, C., Lim, P., Suon, S., Sreng, S., Anderson, J. M., Mao, S., Sam, B., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1314981 · Cited by 2,205
Self-citationA molecular marker of artemisinin-resistant Plasmodium falciparum malaria
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Self-citationMefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number
Price, R. N., Uhlemann, A.-C., Brockman, A., McGready, R., Ashley, E., Phaipun, L., Patel, R., Laing, K., Looareesuwan, S., White, N. J., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16767-6 · Cited by 853
K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates
Straimer, J., Gnädig, N. F., Witkowski, B., Amaratunga, C., Duru, V., Ramadani, A. P., Dacheux, M., Khim, N., Zhang, L., Lam, S., et al. (2015) · Science · doi:10.1126/science.1260867 · Cited by 728
Self-citationGenetic diversity and chloroquine selective sweeps in Plasmodium falciparum
Wootton, J. C., Feng, X., Ferdig, M. T., Cooper, R. A., Mu, J., Baruch, D. I., Magill, A. J., & Su, X.-Z. (2002) · Nature · doi:10.1038/nature00813 · Cited by 722
Chloroquine Resistance in Plasmodium falciparum Malaria Parasites Conferred by pfcrt Mutations
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Self-citationGenome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system
Ghorbal, M., Gorman, M., Macpherson, C. R., Martins, R. M., Scherf, A., & Lopez-Rubio, J.-J. (2014) · Nature Biotechnology · doi:10.1038/nbt.2925 · Cited by 653
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Cited by
Uwimana, A., Legrand, E., Stokes, B. H., Ndikumana, J.-L. M., Warsame, M., Umulisa, N., Ngamije, D., Munyaneza, T., Mazarati, J.-B., Munguti, K., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1005-2 · Cited by 831
Self-citationvan der Pluijm, R. W., Imwong, M., Chau, N. H., Hoa, N. T., Thuy-Nhien, N. T., Thanh, N. V., Jittamala, P., Hanboonkunupakarn, B., Chutasmit, K., Saelow, C., et al. (2019) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(19)30391-3 · Cited by 386
Self-citationMolecular Mechanisms of Drug Resistance in Plasmodium falciparum Malaria
Wicht, K. J., Mok, S., & Fidock, D. A. (2020) · Annual Review of Microbiology · doi:10.1146/annurev-micro-020518-115546 · Cited by 322
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Metadata
- Authors
- Ross, L. S., Dhingra, S. K., Mok, S., Yeo, T., Wicht, K. J., Kümpornsin, K., Takala-Harrison, S., Witkowski, B., Fairhurst, R. M., Ariey, F., Menard, D., & Fidock, D. A.
- Venue
- Nature Communications
- Published
- 2018-08-17
- Volume
- 9
- Issue
- 1
- Pages
- 3314-3314
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2886706562
- Cited by
- 256
- References
- 55
- FWCI
- 25.33
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ross, L. S., Dhingra, S. K., Mok, S., Yeo, T., Wicht, K. J., Kümpornsin, K., Takala-Harrison, S., Witkowski, B., Fairhurst, R. M., Ariey, F., Menard, D., & Fidock, D. A. (2018). Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine. Nature Communications. https://doi.org/10.1038/s41467-018-05652-0
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