ArticleProceedings of the National Academy of Sciences of the United States of America2000
Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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137 citing papers in PubMed, 300 citations in OpenAlex.
- Leishmania major virulence attenuation in vitro: An old conundrum revisited in the omics era.PLoS neglected tropical diseases · 2026Article
- Platelet DKK1 promotes tolerogenic dendritic cells and non-healing responses in cutaneous leishmaniasis.iScience · 2026Article
- A Human Monoclonal Antibody Targeting α-Gal Ameliorates Experimental Cutaneous Leishmaniasis.The Journal of infectious diseases · 2026Article
- Functional Dissection ofToxins · 2026Article
- Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area.Parasites & vectors · 2025Article
- CYP5122A1 encodes an essential sterol C4-methyl oxidase in Leishmania donovani and determines the antileishmanial activity of antifungal azoles.Nature communications · 2024Article
- Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds.Molecules (Basel, Switzerland) · 2024Article
- Activation Pathways of Murine Macrophages by Lipophosphoglycan from Strains ofACS infectious diseases · 2024Article
- Identification of potential novel proteomic markers ofFrontiers in cellular and infection microbiology · 2024Article
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- From classical approaches to new developments in genetic engineering of live attenuated vaccine against cutaneous leishmaniasis: potential and immunization.Frontiers in public health · 2024Review
- Extracellular Vesicles Released byMicroorganisms · 2023Article
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- Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-AttenuatedMicroorganisms · 2023Review
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- C-reactive protein binds to short phosphoglycan repeats ofFrontiers in immunology · 2023Article
- Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose TransporterMicrobiology spectrum · 2022Article
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Leishmania major Strain-Dependent Macrophage Activation Contributes to Pathogenicity in the Absence of Lymphocytes.Microbiology spectrum · 2022Article
- Quantitative single-cell analysis of Leishmania major amastigote differentiation demonstrates variably extended expression of the lipophosphoglycan (LPG) virulence factor in different host cell types.PLoS neglected tropical diseases · 2022Article
77 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protozoan parasites of the genus Leishmania undergo a complex life cycle involving transmission by biting sand flies and replication within mammalian macrophage phagolysosomes. A major component of the Leishmania surface coat is the glycosylphosphatidylinositol (GPI)-anchored polysaccharide called lipophosphoglycan (LPG). LPG has been proposed to play many roles in the infectious cycle, including protection against complement and oxidants, serving as the major ligand for macrophage adhesion, and as a key factor mitigating host responses by deactivation of macrophage signaling pathways. However, all structural domains of LPG are shared by other major surface or secretory products, providing a biochemical redundancy that compromises the ability of in vitro tests to establish whether LPG itself is a virulence factor. To study truly lpg(-) parasites, we generated Leishmania major lacking the gene LPG1 [encoding a putative galactofuranosyl (Gal(f)) transferase] by targeted gene disruption. The lpg1(-) parasites lacked LPG but contained normal levels of related glycoconjugates and GPI-anchored proteins. Infections of susceptible mice and macrophages in vitro showed that these lpg(-) Leishmania were highly attenuated. Significantly and in contrast to previous LPG mutants, reintroduction of LPG1 into the lpg(-) parasites restored virulence. Thus, genetic approaches allow dissection of the roles of this complex family of interrelated parasite virulence factors, and definitively establish the role of LPG itself as a parasite virulence factor. Because the lpg1(-) mutant continue to synthesize bulk GPI-anchored Gal(f)-containing glycolipids other than LPG, a second pathway distinct from the Golgi-associated LPG synthetic compartment must exist.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.