ArticleThe Journal of experimental medicine2015
Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 74 citations in OpenAlex.
- Plasmepsins as Antimalarial Drug Targets-Then, Now, and the Future.Medicinal research reviews · 2026Review
- Host Reticulocyte Redox Attenuation Creates a Protective Niche for Artemisinin Tolerance in Plasmodium falciparum.The Journal of infectious diseases · 2026Article
- Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.The Journal of clinical investigation · 2026Article
- PfATG18 links V-ATPase assembly to endocytic membrane dynamics in malaria parasites.PLoS pathogens · 2026Article
- Hemoglobin Digestion Genes Are Conserved in Lizard-InfectiveEcology and evolution · 2026Article
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- Heme as activator and target for artemisinin: Towards multiple pharmacological bioactivity.Biochemistry and biophysics reports · 2026Review
- Experimental vaccination by single dose sporozoite injection of blood-stage attenuated malaria parasites.EMBO molecular medicine · 2024Article
- Magneto-optical assessment of Plasmodium parasite growth via hemozoin crystal size.Scientific reports · 2024Article
- Article
- Antimalarial and antioxidant activities of novel artesunate-ellagic acid hybrid compoundFrontiers in pharmacology · 2024Article
- Review
- pH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle.Nature communications · 2023Article
- Morphometric and molecular characterization of an unpigmented haemosporidian parasite in the Neotropical turnip-tailed gecko (Parasitology · 2023Article
- Article
- An Alternative Autophagy-Related Mechanism of Chloroquine Drug Resistance in the Malaria Parasite.Antimicrobial agents and chemotherapy · 2022Article
- Genetic and chemical validation ofeLife · 2022Article
- Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice.Nature communications · 2022Article
- The Role of the Iron Protoporphyrins Heme and Hematin in the Antimalarial Activity of Endoperoxide Drugs.Pharmaceuticals (Basel, Switzerland) · 2022Review
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Authors and funding
24 authors at 8 institutions in 6 countries.
Funding
Abstract
Most studies on malaria-parasite digestion of hemoglobin (Hb) have been performed using P. falciparum maintained in mature erythrocytes, in vitro. In this study, we examine Plasmodium Hb degradation in vivo in mice, using the parasite P. berghei, and show that it is possible to create mutant parasites lacking enzymes involved in the initial steps of Hb proteolysis. These mutants only complete development in reticulocytes and mature into both schizonts and gametocytes. Hb degradation is severely impaired and large amounts of undigested Hb remains in the reticulocyte cytoplasm and in vesicles in the parasite. The mutants produce little or no hemozoin (Hz), the detoxification by-product of Hb degradation. Further, they are resistant to chloroquine, an antimalarial drug that interferes with Hz formation, but their sensitivity to artesunate, also thought to be dependent on Hb degradation, is retained. Survival in reticulocytes with reduced or absent Hb digestion may imply a novel mechanism of drug resistance. These findings have implications for drug development against human-malaria parasites, such as P. vivax and P. ovale, which develop inside reticulocytes.
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