ArticlePloS one2014
Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Temporal multi-tissue profiling reveals metabolites linked to immune response and malaria parasitemia control.iScience · 2026Article
- A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite.Nature communications · 2025Article
- Elevated NADNature communications · 2025Article
- Synthesis, Biological, and Computational Evaluations of Conformationally Restricted NAD-Mimics as Discriminant Inhibitors of Human NMN-Adenylyltransferase Isozymes.Pharmaceuticals (Basel, Switzerland) · 2024Article
- NAD activates olfactory receptor 1386 to regulate type I interferon responses inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hungry for control: metabolite signaling to chromatin in Plasmodium falciparum.Current opinion in microbiology · 2024Review
- Host metabolomic responses in recurrent P. vivax malaria.Scientific reports · 2024Article
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
- Protein-Targeting Drug Discovery.Biomolecules · 2023Article
- Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets.PLoS pathogens · 2021Review
- Pathogen induced subversion of NADCell death discovery · 2021Article
- Uncovering the Role of Metabolism in Oomycete-Host Interactions Using Genome-Scale Metabolic Models.Frontiers in microbiology · 2021Review
- Article
- Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival.PLoS pathogens · 2020Article
- Kinetic and oligomeric study ofHeliyon · 2020Article
- Analysis of the active fraction of IranianIranian journal of basic medical sciences · 2020Article
- Vitamin and cofactor acquisition in apicomplexans: SynthesisThe Journal of biological chemistry · 2020Review
- The Prospective Synergy of Antitubercular Drugs With NAD Biosynthesis Inhibitors.Frontiers in microbiology · 2020Review
- Novel Antimycobacterial Compounds Suppress NAD Biogenesis by Targeting a Unique Pocket of NaMN Adenylyltransferase.ACS chemical biology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P. falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT), is essential for NAD+ metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT in vitro and demonstrate its ability to genetically complement the closely related Escherichia coli NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD+ metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds.
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