ArticleMolecular microbiology2012
Dissecting the role of glutathione biosynthesis in Plasmodium falciparum.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Association of reduced glutathione levels with Plasmodium falciparum and Plasmodium vivax malaria: a systematic review and meta-analysis.Scientific reports · 2023Pooled it
- Glutathione redox system as a therapeutic target for Plasmodium: Opportunities, Challenges, and future perspectives.Folia microbiologica · 2026Review
- Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation ofAntimicrobial agents and chemotherapy · 2025Article
- Article
- Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs.Antimicrobial agents and chemotherapy · 2024Article
- Metabolic changes that allowFrontiers in parasitology · 2024Article
- Reactive Oxygen Species as the Brainbox in Malaria Treatment.Antioxidants (Basel, Switzerland) · 2021Review
- Redox interactome in malaria parasite Plasmodium falciparum.Parasitology research · 2021Review
- Glutaredoxin 1 Deficiency Leads to Microneme Protein-Mediated Growth Defects inFrontiers in microbiology · 2020Article
- Structure-Based Screening ofFrontiers in pharmacology · 2020Article
- Article
- Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.BMC genomics · 2017Article
- Major Polymorphisms of Genes Involved in Homocysteine Metabolism in Malaria Patients in Ouagadougou, Burkina Faso.Malaria research and treatment · 2017Article
- Role of Zn doping in oxidative stress mediated cytotoxicity of TiO2 nanoparticles in human breast cancer MCF-7 cells.Scientific reports · 2016Article
- Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage.Free radical biology & medicine · 2016Article
- Inhibition of Glutathione Biosynthesis Sensitizes Plasmodium berghei to Antifolates.Antimicrobial agents and chemotherapy · 2016Article
- Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery.Molecules (Basel, Switzerland) · 2015Review
- Role and Regulation of Glutathione Metabolism in Plasmodium falciparum.Molecules (Basel, Switzerland) · 2015Review
- Host reticulocytes provide metabolic reservoirs that can be exploited by malaria parasites.PLoS pathogens · 2015Article
- Biochemical and structural characterization of the apicoplast dihydrolipoamide dehydrogenase of Plasmodium falciparum.Bioscience reports · 2015Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Glutathione (γ-glutamylcysteinyl-glycine, GSH) has vital functions as thiol redox buffer and cofactor of antioxidant and detoxification enzymes. Plasmodium falciparum possesses a functional GSH biosynthesis pathway and contains mM concentrations of the tripeptide. It was impossible to delete in P. falciparum the genes encoding γ-glutamylcysteine synthetase (γGCS) or glutathione synthetase (GS), the two enzymes synthesizing GSH, although both gene loci were not refractory to recombination. Our data show that the parasites cannot compensate for the loss of GSH biosynthesis via GSH uptake. This suggests an important if not essential function of GSH biosynthesis pathway for the parasites. Treatment with the irreversible inhibitor of γGCS L-buthionine sulfoximine (BSO) reduced intracellular GSH levels in P. falciparum and was lethal for their intra-erythrocytic development, corroborating the suggestion that GSH biosynthesis is important for parasite survival. Episomal expression of γgcs in P. falciparum increased tolerance to BSO attributable to increased levels of γGCS. Concomitantly expression of glutathione reductase was reduced leading to an increased GSH efflux. Together these data indicate that GSH levels are tightly regulated by a functional GSH biosynthesis and the reduction of GSSG.
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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.