ArticleMolecular and biochemical parasitology2019
Farnesyl pyrophosphate synthase is essential for the promastigote and amastigote stages in Leishmania major.
Article in Molecular and biochemical parasitology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 23 citations in OpenAlex.
- Molecular docking and simulation analysis of selected herbal compounds against GP63, FPPS, and NMT, three importantResearch in pharmaceutical sciences · 2025Article
- Knockdown of farnesyl pyrophosphate synthetase gene TuFPPS by RNAi extends quiescent period and halts molting of the spider mite, Tetranychus urticae.Experimental & applied acarology · 2025Article
- Article
- CYP5122A1 encodes an essential sterol C4-methyl oxidase in Leishmania donovani and determines the antileishmanial activity of antifungal azoles.Nature communications · 2024Article
- Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.PLoS pathogens · 2023Article
- Ethanolaminephosphate cytidyltransferase is essential for survival, lipid homeostasis and stress tolerance inbioRxiv : the preprint server for biology · 2023Article
- The Golgi-localized sphingosine-1-phosphate phosphatase is indispensable for Leishmania major.Scientific reports · 2022Article
- Article
- Drug combinations as effective anti-leishmanials against drug resistantRSC medicinal chemistry · 2020Article
- Identifying Structural Determinants of Product Specificity inBiochemistry · 2020Article
- Bisphosphonate-Based Molecules as Potential New Antiparasitic Drugs.Molecules (Basel, Switzerland) · 2020Review
- Multi-target heteroleptic palladium bisphosphonate complexes.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Isoprenoid synthesis provides a diverse class of biomolecules including sterols, dolichols, ubiquinones and prenyl groups. The enzyme farnesyl pyrophosphate synthase (FPPS) catalyzes the formation of farnesyl pyrophosphate, a key intermediate for the biosynthesis of all isoprenoids. In Leishmania, FPPS is considered the main target of nitrogen containing bisphosphonates, yet the essentiality of this enzyme remains untested. Using a facilitated knockout approach, we carried out the genetic analysis of FPPS in Leishmania major. Our data indicated that chromosomal null mutants for FPPS could only be generated in presence of an episomally expressed FPPS. Long-term retention of the episome by the chromosomal FPPS-null mutants in culture and in infected BALB/c mice suggests that FPPS is indispensable. In addition, applying negative selection pressure failed to induce the loss of ectopic FPPS in the chromosomal FPPS-null mutants, although it led to significant growth delay in culture and in mice. Together, our findings have confirmed the essentiality of FPPS in both promastigotes and amastigotes in L. major and thus validate its potential as a drug target for the treatment of cutaneous leishmaniasis.
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