title: The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages.
abstract: Glycosylation is an important posttranslational protein modification in all eukaryotes. Besides glycosylphosphatidylinositol (GPI) anchors and N-glycosylation, O-fucosylation has been recently reported in key sporozoite proteins of the malaria parasite. Previous analyses showed the presence of GDP-fucose (GDP-Fuc), the precursor for all fucosylation reactions, in the blood stages of Plasmodium falciparum. The GDP-Fuc de novo pathway, which requires the action of GDP-mannose 4,6-dehydratase (GMD) and GDP-L-fucose synthase (FS), is conserved in the parasite genome, but the importance of fucose metabolism for the parasite is unknown. To functionally characterize the pathway we generated a PfGMD mutant and analyzed its phenotype. Although the labelling by the fucose-binding Ulex europaeus agglutinin I (UEA-I) was completely abrogated, GDP-Fuc was still detected in the mutant. This unexpected result suggests the presence of an alternative mechanism for maintaining GDP-Fuc in the parasite. Furthermore, PfGMD null mutant exhibited normal growth and invasion rates, revealing that the GDP-Fuc de novo metabolic pathway is not essential for the development in culture of the malaria parasite during the asexual blood stages. Nonetheless, the function of this metabolic route and the GDP-Fuc pool that is generated during this stage may be important for gametocytogenesis and sporogonic development in the mosquito.
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Sanz
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: López-Gutiérrez
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 72 East Concord St, Boston, MA 02118, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bandini
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Damerow
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School, Boston MA 02115, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Absalon
authors.affiliation: The University of Florida Emerging Pathogens Institute, Department of Infectious Diseases &Pathology, Gainesville FL 32611, USA.
authors.forename: Rhoel R
authors.initials: RR
authors.lastname: Dinglasan
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 72 East Concord St, Boston, MA 02118, USA.
authors.forename: John
authors.initials: J
authors.lastname: Samuelson
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Izquierdo
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics; D005643:Fucose / Q000378:metabolism*; D018503:Genome, Protozoan / Q000235:genetics; D006001:Glycoconjugates / Q000378:metabolism*; D006154:Guanosine Diphosphate Fucose / Q000096:biosynthesis*; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D010641:Phenotype; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D006001:Glycoconjugates; D015800:Protozoan Proteins; D006154:Guanosine Diphosphate Fucose; D005643:Fucose; D006836:Hydro-Lyases; C044971:GDPmannose 4,6-dehydratase