ArticlePLoS pathogens2016
Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- Identification of α-Azacyclic Acetamide-Based Inhibitors ofACS infectious diseases · 2025Article
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- Article
- A Soluble Expression Construct of the Isolated Catalytic Domain of Plasmodium falciparum ATP4 Exhibits ATPase Activity Independent of a γ-Phosphate Receiving Aspartate.Molecular microbiology · 2025Article
- Mutational analysis of an antimalarial drug target,Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TheScience advances · 2024Article
- Antimalarial and Immunomodulatory Activities ofScientifica · 2024Article
- The enemy within: lipid asymmetry in intracellular parasite-host interactions.Emerging topics in life sciences · 2023Review
- Conditional permeabilization of the P. falciparum plasma membrane in infected cells links cation influx to reduced membrane integrity.PloS one · 2023Article
- A G358S mutation in the Plasmodium falciparum NaNature communications · 2022Article
- Selective Inhibition of Plasmodium falciparum ATPase 6 by Artemisinins and Identification of New Classes of Inhibitors after Expression in Yeast.Antimicrobial agents and chemotherapy · 2022Article
- Prefoldin subunit 6 of Plasmodium falciparum binds merozoite surface protein-1.FEBS open bio · 2022Article
- Dramatic Consequences of Reducing Erythrocyte Membrane Cholesterol on Plasmodium falciparum.Microbiology spectrum · 2022Article
- Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites.The Journal of biological chemistry · 2022Article
- Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure.Scientific reports · 2022Article
- Article
- The role of cholesterol in invasion and growth of malaria parasites.Frontiers in cellular and infection microbiology · 2022Review
- The Functioning of NaCells · 2020Review
- Diverse Chemical Compounds Target Plasmodium falciparum Plasma Membrane Lipid Homeostasis.ACS infectious diseases · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i) within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2), glycosylphosphotidylinositol (GPI)-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble "rhoptries" and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise.
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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.