ArticlePLoS pathogens2014
Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91 citing papers in PubMed, 185 citations in OpenAlex.
- Queuosine tRNA modification regulates translational adaptation and virulence of Leishmania mexicana.PLoS biology · 2026Article
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- Targeting mitochondrial bioenergetics: the "Achilles' heel" of Leishmania.Parasites & vectors · 2026Article
- Identification of transporters essential for survival of Leishmania promastigotes in the digestive tract of sand flies.PLoS pathogens · 2026Article
- Investigation of viscerotropism-associated genes inFrontiers in microbiology · 2026Article
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- Leishmania major Dihydrolipoyl dehydrogenase (DLD) is a key metabolic enzyme that drives parasite proliferation, pathology and host immune response.PLoS pathogens · 2025Article
- Synthesis and in vitro antitrypanosomatid activity of novel 5-nitroindole-rhodanine conjugates.Future medicinal chemistry · 2025Article
- TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.Nature communications · 2025Article
- Integration of hepatic lipidomics and transcriptomics reveals dysregulation of lipid metabolism in a golden hamster model of visceral leishmaniasis.Frontiers in immunology · 2025Article
- The repertoire of iron superoxide dismutases fromJournal of enzyme inhibition and medicinal chemistry · 2024Article
- CYP5122A1 encodes an essential sterol C4-methyl oxidase in Leishmania donovani and determines the antileishmanial activity of antifungal azoles.Nature communications · 2024Article
- Evolutionary divergent clusters of transcribed extinct truncated retroposons drive low mRNA expression and developmental regulation in the protozoan Leishmania.BMC biology · 2024Article
- Distribution and Functional Analysis of Isocitrate Dehydrogenases across Kinetoplastids.Genome biology and evolution · 2024Article
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- Molecular Mechanisms of Persistence in Protozoan Parasites.Microorganisms · 2023Review
- Metabolomics analysis of visceral leishmaniasis based on urine of golden hamsters.Parasites & vectors · 2023Article
- Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.PLoS pathogens · 2023Article
- Arsinothricin InhibitsMicroorganisms · 2023Article
31 more citing papers are in PubMed but not listed here.
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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
Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13)C-stable isotope resolved metabolomics and (2)H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate) and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA) cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.
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