ArticleMolecular and cellular biology2001
Glycosylation defects and virulence phenotypes of Leishmania mexicana phosphomannomutase and dolicholphosphate-mannose synthase gene deletion mutants.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 87 citations in OpenAlex.
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- Mapping Alterations Induced by Long-Term Axenic Cultivation ofFrontiers in cellular and infection microbiology · 2019Article
- Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana.PLoS pathogens · 2018Article
- Discovery and Genetic Validation of Chemotherapeutic Targets for Chagas' Disease.Frontiers in cellular and infection microbiology · 2018Review
- Simple and efficient synthesis of 5'-aryl-5'-deoxyguanosine analogs by azide-alkyne click reaction and their antileishmanial activities.Molecular diversity · 2016Article
- Cysteine Peptidase B Regulates Leishmania mexicana Virulence through the Modulation of GP63 Expression.PLoS pathogens · 2016Article
- Depletion of UDP-Glucose and UDP-Galactose Using a Degron System Leads to Growth Cessation of Leishmania major.PLoS neglected tropical diseases · 2015Article
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- Unveiling the intracellular survival gene kit of trypanosomatid parasites.PLoS pathogens · 2014Review
- Characterization of Leishmania major phosphatidylethanolamine methyltransferases LmjPEM1 and LmjPEM2 and their inhibition by choline analogs.Molecular and biochemical parasitology · 2014Article
- Leishmania lipophosphoglycan: how to establish structure-activity relationships for this highly complex and multifunctional glycoconjugate?Frontiers in cellular and infection microbiology · 2014Review
- Induction of a stringent metabolic response in intracellular stages of Leishmania mexicana leads to increased dependence on mitochondrial metabolism.PLoS pathogens · 2014Article
- In-silico Leishmania target selectivity of antiparasitic terpenoids.Molecules (Basel, Switzerland) · 2013Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania parasites synthesize an abundance of mannose (Man)-containing glycoconjugates thought to be essential for virulence to the mammalian host and for viability. These glycoconjugates include lipophosphoglycan (LPG), proteophosphoglycans (PPGs), glycosylphosphatidylinositol (GPI)-anchored proteins, glycoinositolphospholipids (GIPLs), and N-glycans. A prerequisite for their biosynthesis is an ample supply of the Man donors GDP-Man and dolicholphosphate-Man. We have cloned from Leishmania mexicana the gene encoding the enzyme phosphomannomutase (PMM) and the previously described dolicholphosphate-Man synthase gene (DPMS) that are involved in Man activation. Surprisingly, gene deletion experiments resulted in viable parasite lines lacking the respective open reading frames (DeltaPMM and DeltaDPMS), a result against expectation and in contrast to the lethal phenotype observed in gene deletion experiments with fungi. L. mexicana DeltaDPMS exhibits a selective defect in LPG, protein GPI anchor, and GIPL biosynthesis, but despite the absence of these structures, which have been implicated in parasite virulence and viability, the mutant remains infectious to macrophages and mice. By contrast, L. mexicana DeltaPMM are largely devoid of all known Man-containing glycoconjugates and are unable to establish an infection in mouse macrophages or the living animal. Our results define Man activation leading to GDP-Man as a virulence pathway in Leishmania.
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