ArticlePLoS pathogens2018
Mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- TheScience advances · 2026Article
- Thiazole substitution of a labile amide bond-a new option toward antiplasmodial pantothenamide-mimics.Antimicrobial agents and chemotherapy · 2025Article
- Characterization of the Sodium Multi-Vitamin Transporter in the MosquitoBiomolecules · 2025Article
- Identification and characterization of thiamine analogs with antiplasmodial activity.Antimicrobial agents and chemotherapy · 2024Article
- Starving the Beast: Limiting Coenzyme A Biosynthesis to Prevent Disease and Transmission in Malaria.International journal of molecular sciences · 2023Review
- Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183.Nature communications · 2022Article
- A new mass spectral library for high-coverage and reproducible analysis of the Plasmodium falciparum-infected red blood cell proteome.GigaScience · 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
- A novel heteromeric pantothenate kinase complex in apicomplexan parasites.PLoS pathogens · 2021Article
- Activation ofBiomolecules · 2021Article
- Characterization ofFrontiers in cellular and infection microbiology · 2021Article
- The Pathophysiological Role of CoA.International journal of molecular sciences · 2020Review
- Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of the Malaria Parasite Life Cycle.Cell host & microbe · 2020Article
- Multi-omic Characterization of the Mode of Action of a Potent New Antimalarial Compound, JPC-3210, AgainstMolecular & cellular proteomics : MCP · 2020Article
- Vitamin and cofactor acquisition in apicomplexans: SynthesisThe Journal of biological chemistry · 2020Review
- Overcoming synthetic challenges in targeting coenzyme A biosynthesis with the antimicrobial natural product CJ-15,801.MedChemComm · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The malaria-causing blood stage of Plasmodium falciparum requires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the parasite by targeting CoA biosynthesis/utilisation. Their mechanism of action, however, remains unknown. Here, we show that parasites pressured with pantothenol or CJ-15,801 become resistant to these analogues. Whole-genome sequencing revealed mutations in one of two putative PanK genes (Pfpank1) in each resistant line. These mutations significantly alter PfPanK activity, with two conferring a fitness cost, consistent with Pfpank1 coding for a functional PanK that is essential for normal growth. The mutants exhibit a different sensitivity profile to recently-described, potent, antiplasmodial pantothenate analogues, with one line being hypersensitive. We provide evidence consistent with different pantothenate analogue classes having different mechanisms of action: some inhibit CoA biosynthesis while others inhibit CoA-utilising enzymes.
Indexed as
Identifiers
What OpenQuestion holds
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.