Drug resistance is an obstacle to global malaria control, as evidenced by the recent emergence and rapid spread of delayed artemisinin (ART) clearance by mutant forms of the
This content will become publicly available on September 18, 2025
The European corn borer (
- PAR ID:
- 10542877
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Insect Molecular Biology
- ISSN:
- 0962-1075
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Pf Kelch13 protein in Southeast Asia. Identifying genetic determinants of ART resistance in African-derived parasites is important for surveillance and for understanding the mechanism of resistance. In this study, we carried out long-term in vitro selection of two recently isolated West African parasites (from Pikine and Thiès, Senegal) with increasing concentrations of dihydroartemisinin (DHA), the biologically active form of ART, over a 4-y period. We isolated two parasite clones, one from each original isolate, that exhibited enhanced survival to DHA in the ring-stage survival assay. Whole-genome sequence analysis identified 10 mutations in seven different genes. We chose to focus on the gene encodingPf Coronin, a member of the WD40-propeller domain protein family, because mutations in this gene occurred in both independent selections, and the protein shares the β-propeller motif withPf Kelch13 protein. For functional validation, whenpfcoronin mutations were introduced into the parental parasites by CRISPR/Cas9-mediated gene editing, these mutations were sufficient to reduce ART susceptibility in the parental lines. The discovery of a second gene for ART resistance may yield insights into the molecular mechanisms of resistance. It also suggests thatpfcoronin mutants could emerge as a nonkelch13 type of resistance to ART in natural settings. -
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