ArticleMolecular microbiology2012
Mechanisms of in vitro resistance to dihydroartemisinin in Plasmodium falciparum.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 97 citations in OpenAlex.
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- Autophagy Underlies the Proteostasis Mechanisms of Artemisinin Resistance in P. falciparum Malaria.mBio · 2022Article
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- Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response.Communications biology · 2022Article
- Impact of Drug Pressure versus Limited Access to Drug in Malaria Control: The Dilemma.Medicines (Basel, Switzerland) · 2022Review
- Prevalence of malaria resistance-associated mutations inFrontiers in microbiology · 2022Article
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- A systems-level gene regulatory network model for Plasmodium falciparum.Nucleic acids research · 2021Article
- Daily rhythms of both host and parasite affect antimalarial drug efficacy.Evolution, medicine, and public health · 2021Article
- Transmission of Artemisinin-Resistant Malaria Parasites to Mosquitoes under Antimalarial Drug Pressure.Antimicrobial agents and chemotherapy · 2020Article
- Modulation of Triple Artemisinin-Based Combination Therapy Pharmacodynamics byACS pharmacology & translational science · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The recent reports of artemisinin (ART) resistance in the Thai-Cambodian border area raise a serious concern on the long-term efficacy of ARTs. To elucidate the resistance mechanisms, we performed in vitro selection with dihydroartemisinin (DHA) and obtained two parasite clones from Dd2 with more than 25-fold decrease in susceptibility to DHA. The DHA-resistant clones were more tolerant of stressful growth conditions and more resistant to several commonly used antimalarial drugs than Dd2. The result is worrisome as many of the drugs are currently used as ART partners in malaria control. This study showed that the DHA resistance is not limited to ring stage, but also occurred in trophozoites and schizonts. Microarray and biochemical analyses revealed pfmdr1 amplification, elevation of the antioxidant defence network, and increased expression of many chaperones in the DHA-resistant parasites. Without drug pressure, the DHA-resistant parasites reverted to sensitivity in approximately 8 weeks, accompanied by de-amplification of pfmdr1 and reduced antioxidant activities. The parallel decrease and increase in pfmdr1 copy number and antioxidant activity and the up and down of DHA sensitivity strongly suggest that pfmdr1 and antioxidant defence play a role in in vitro resistance to DHA, providing potential molecular markers for ART resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.