ArticleThe Journal of biological chemistry2013
Identification and functional analysis of the primary pantothenate transporter, PfPAT, of the human malaria parasite Plasmodium falciparum.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Critical interdependencies between Plasmodium nutrient flux and drugs.Trends in parasitology · 2023Review
- Starving the Beast: Limiting Coenzyme A Biosynthesis to Prevent Disease and Transmission in Malaria.International journal of molecular sciences · 2023Review
- Continuous In Vitro Culture ofCells · 2023Article
- An Alternative Culture Medium for Continuous In Vitro Propagation of the Human PathogenPathogens (Basel, Switzerland) · 2022Article
- Pantothenate biosynthesis is critical for chronic infection by the neurotropic parasite Toxoplasma gondii.Nature communications · 2022Article
- Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets.PLoS pathogens · 2021Review
- Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption.The EMBO journal · 2021Article
- How Malaria Parasites Acquire Nutrients From Their Host.Frontiers in cell and developmental biology · 2021Review
- Characterization ofFrontiers in cellular and infection microbiology · 2021Article
- Vitamin and cofactor acquisition in apicomplexans: SynthesisThe Journal of biological chemistry · 2020Review
- NMR metabolomics reveals effects ofGut pathogens · 2019Article
- The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation.Scientific reports · 2017Article
- Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.Nature communications · 2017Article
- Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito.Scientific reports · 2016Article
- A Putative Small Solute Transporter Is Responsible for the Secretion of G377 and TRAP-Containing Secretory Vesicles during Plasmodium Gamete Egress and Sporozoite Motility.PLoS pathogens · 2016Article
- Characterization of Plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening.Molecular microbiology · 2016Article
- Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite.Nature communications · 2016Article
- Targeting protein translation, RNA splicing, and degradation by morpholino-based conjugates in Plasmodium falciparum.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Novel pantothenate derivatives for anti-malarial chemotherapy.Malaria journal · 2015Article
- Identification of inhibitors of Plasmodium falciparum RuvB1 helicase using biochemical assays.Protoplasma · 2015Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The human malaria parasite Plasmodium falciparum is absolutely dependent on the acquisition of host pantothenate for its development within human erythrocytes. Although the biochemical properties of this transport have been characterized, the molecular identity of the parasite-encoded pantothenate transporter remains unknown. Here we report the identification and functional characterization of the first protozoan pantothenate transporter, PfPAT, from P. falciparum. We show using cell biological, biochemical, and genetic analyses that this transporter is localized to the parasite plasma membrane and plays an essential role in parasite intraerythrocytic development. We have targeted PfPAT to the yeast plasma membrane and showed that the transporter complements the growth defect of the yeast fen2Δ pantothenate transporter-deficient mutant and mediates the entry of the fungicide drug, fenpropimorph. Our studies in P. falciparum revealed that fenpropimorph inhibits the intraerythrocytic development of both chloroquine- and pyrimethamine-resistant P. falciparum strains with potency equal or better than that of currently available pantothenate analogs. The essential function of PfPAT and its ability to deliver both pantothenate and fenpropimorph makes it an attractive target for the development and delivery of new classes of antimalarial drugs.
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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.