ArticlePloS one2013
Experimental Genetics of Plasmodium berghei NFU in the Apicoplast Iron-Sulfur Cluster Biogenesis Pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 21 citations in OpenAlex.
- Complex Endosymbiosis II: The Nonphotosynthetic Plastid of Apicomplexa Parasites (The Apicoplast) and Its Integrated Metabolism.Methods in molecular biology (Clifton, N.J.) · 2024Article
- TheeLife · 2023Article
- Roles of Ferredoxin-Dependent Proteins in the Apicoplast of Plasmodium falciparum Parasites.mBio · 2021Article
- Engineering of Genetically Arrested Parasites (GAPs) For a Precision Malaria Vaccine.Frontiers in cellular and infection microbiology · 2017Review
- Recent advances in the Suf Fe-S cluster biogenesis pathway: Beyond the Proteobacteria.Biochimica et biophysica acta · 2015Review
- Sulfur mobilization for Fe-S cluster assembly by the essential SUF pathway in the Plasmodium falciparum apicoplast and its inhibition.Antimicrobial agents and chemotherapy · 2014Article
- Article
- Identification of vital and dispensable sulfur utilization factors in the Plasmodium apicoplast.PloS one · 2014Article
- Improved efficacy of fosmidomycin against Plasmodium and Mycobacterium species by combination with the cell-penetrating peptide octaarginine.Antimicrobial agents and chemotherapy · 2013Article
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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
Eukaryotic pathogens of the phylum Apicomplexa contain a non-photosynthetic plastid, termed apicoplast. Within this organelle distinct iron-sulfur [Fe-S] cluster proteins are likely central to biosynthesis pathways, including generation of isoprenoids and lipoic acid. Here, we targeted a nuclear-encoded component of the apicoplast [Fe-S] cluster biosynthesis pathway by experimental genetics in the murine malaria parasite Plasmodium berghei. We show that ablation of the gene encoding a nitrogen fixation factor U (NifU)-like domain containing protein (NFUapi) resulted in parasites that were able to complete the entire life cycle indicating redundant or non-essential functions. nfu (-) parasites displayed reduced merosome formation in vitro, suggesting that apicoplast NFUapi plays an auxiliary role in establishing a blood stage infection. NFUapi fused to a combined fluorescent protein-epitope tag delineates the Plasmodium apicoplast and was tested to revisit inhibition of liver stage development by azithromycin and fosmidomycin. We show that the branched apicoplast signal is entirely abolished by azithromycin treatment, while fosmidomycin had no effect on apicoplast morphology. In conclusion, our experimental genetics analysis supports specialized and/or redundant role(s) for NFUapi in the [Fe-S] cluster biosynthesis pathway in the apicoplast of a malarial parasite.
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