14 research outputs found
The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in <i>Plasmodium</i> asexual blood stages
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
Maternal TLR4 and NOD2 Gene Variants, Pro-Inflammatory Phenotype and Susceptibility to Early-Onset Preeclampsia and HELLP Syndrome
Background: Altered maternal inflammatory responses play a role in the development of preeclampsia and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. We examined whether allelic variants of the innate immune receptors toli-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain (NOD2), that impair the inflammatory response to endotexin are related to preeclampsia and HELLP syndrome. Methods and Finding: We determined five common mutations in TLR4 (D299G and T399I and NOD2 (R70W, G908R and L1007fs) in 340 primiparous women with a histo