ArticleInfection and immunity2016
Distinct Prominent Roles for Enzymes of Plasmodium berghei Heme Biosynthesis in Sporozoite and Liver Stage Maturation.
Article in Infection and immunity, 2016. 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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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- The Plasmodium heme detoxification protein functions in mitochondrial protein synthesis.Nature communications · 2026Article
- Acyl Carrier Protein is Essential for Apicoplast Biogenesis in Malaria Parasites Independent of Fatty Acid Synthesis.bioRxiv : the preprint server for biology · 2026Article
- Biogenesis of CytochromesACS infectious diseases · 2025Article
- Biogenesis of cytochromesbioRxiv : the preprint server for biology · 2024Article
- Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.Nature communications · 2024Article
- Roles of the apicoplast across the life cycles of rodent and human malaria parasites.The Journal of eukaryotic microbiology · 2022Review
- Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice.Nature communications · 2022Article
- Structure-based pharmacophore modeling, virtual screening, and molecular dynamics simulation studies for identification ofFrontiers in medicine · 2022Article
- Characterization of the apicoplast-localized enzymeThe Journal of biological chemistry · 2020Article
- Article
- Vitamin and cofactor acquisition in apicomplexans: SynthesisThe Journal of biological chemistry · 2020Review
- Host Porphobilinogen Deaminase Deficiency Confers Malaria Resistance inFrontiers in cellular and infection microbiology · 2020Article
- Plasmodium heme biosynthesis: To be or not to be essential?PLoS pathogens · 2017Review
- Article
- Engineering of Genetically Arrested Parasites (GAPs) For a Precision Malaria Vaccine.Frontiers in cellular and infection microbiology · 2017Review
- Interaction betweenFrontiers in cellular and infection microbiology · 2017Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malarial parasites have evolved complex regulation of heme supply and disposal to adjust to heme-rich and -deprived host environments. In addition to its own pathway for heme biosynthesis, Plasmodium likely harbors mechanisms for heme scavenging from host erythrocytes. Elaborate compartmentalization of de novo heme synthesis into three subcellular locations, including the vestigial plastid organelle, indicates critical roles in life cycle progression. In this study, we systematically profile the essentiality of heme biosynthesis by targeted gene deletion of enzymes in early steps of this pathway. We show that disruption of endogenous heme biosynthesis leads to a first detectable defect in oocyst maturation and sporogony in the Anopheles vector, whereas blood stage propagation, colonization of mosquito midguts, or initiation of oocyst development occurs indistinguishably from that of wild-type parasites. Although sporozoites are produced by parasites lacking an intact pathway for heme biosynthesis, they are absent from mosquito salivary glands, indicative of a vital role for heme biosynthesis only in sporozoite maturation. Rescue of the first defect in sporogony permitted analysis of potential roles in liver stages. We show that liver stage parasites benefit from but do not strictly depend upon their own aminolevulinic acid synthase and that they can scavenge aminolevulinic acid from the host environment. Together, our experimental genetics analysis of Plasmodium enzymes for heme biosynthesis exemplifies remarkable shifts between the use of endogenous and host resources during life cycle progression.
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