ArticleScientific reports2017
A disrupted transsulphuration pathway results in accumulation of redox metabolites and induction of gametocytogenesis in malaria.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 60 citations in OpenAlex.
- Shared host, distinct invaders: metabolomic footprints of plasmodium and babesia in host red cells.Current opinion in hematology · 2025Review
- Evolutionary Trajectory ofBiomedicines · 2025Review
- Variable surface antigen expression, virulence, and persistent infection byMicrobiology and molecular biology reviews : MMBR · 2025Review
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- Sexual differentiation in human malaria parasites is regulated by competition between phospholipid metabolism and histone methylation.Nature microbiology · 2023Article
- The human malaria parasiteProceedings of the National Academy of Sciences of the United States of America · 2023Article
- High-throughput analysis of the transcriptional patterns of sexual genes in malaria.Parasites & vectors · 2023Article
- Plasmodium falciparum Sexual Commitment Rate Variation among Clinical Isolates and Diverse Laboratory-Adapted Lines.Microbiology spectrum · 2022Article
- Recent metabolomic developments for antimalarial drug discovery.Parasitology research · 2022Review
- Identification and characterization of extracellular vesicles from red cells infected withFrontiers in cellular and infection microbiology · 2022Article
- Article
- Metabolic regulation of sexual commitment in Plasmodium falciparum.Current opinion in microbiology · 2020Review
- Mining the Human Host Metabolome Toward an Improved Understanding of Malaria Transmission.Frontiers in microbiology · 2020Review
- ApiAP2 Transcription Factors in Apicomplexan Parasites.Pathogens (Basel, Switzerland) · 2019Review
- Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria.Scientific reports · 2019Article
- Essential metabolism for a minimal cell.eLife · 2019Article
- Identification of a putative methyltransferase gene of Babesia bigemina as a novel molecular biomarker uniquely expressed in parasite tick stages.Parasites & vectors · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intra-erythrocytic growth of malaria parasite is known to induce redox stress. In addition to haem degradation which generates reactive oxygen species (ROS), the parasite is also thought to efflux redox active homocysteine. To understand the basis underlying accumulation of homocysteine, we have examined the transsulphuration (TS) pathway in the parasite, which is known to convert homocysteine to cysteine in higher eukaryotes. Our bioinformatic analysis revealed absence of key enzymes in the biosynthesis of cysteine namely cystathionine-β-synthase and cystathionine-γ-lyase in the parasite. Using mass spectrometry, we confirmed the absence of cystathionine, which is formed by enzymatic conversion of homocysteine thereby confirming truncation of TS pathway. We also quantitated levels of glutathione and homocysteine in infected erythrocytes and its spent medium. Our results showed increase in levels of these metabolites intracellularly and in culture supernatants. Our results provide a mechanistic basis for the long-known occurrence of hyperhomocysteinemia in malaria. Most importantly we find that homocysteine induces the transcription factor implicated in gametocytogenesis namely AP2-G and consequently triggers sexual stage conversion. We confirmed this observation both in vitro using Plasmodium falciparum cultures, and in vivo in the mouse model of malaria. Our study implicates homocysteine as a potential physiological trigger of gametocytogenesis.
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