Protein glycosylation in the malaria parasite

The nature and extent of glycosylation in Plasmodium falciparum has long be en controversial. It has been widely believed that O-glycosylation is the m ajor carbohydrate modification in the intraerythrocytic stage of P. falcipa rum and that the parasite has no N-glycosylation capacity. Contrary to this , recent studies have demonstrated that P. falciparum has a low N-glycosyla tion capability, and O-glycosylation is either absent or present at an extr emely low level, whereas glycosylphosphatidylinositol (GPI) anchor modifica tion is common and is the major carbohydrate modification in parasite prote ins. The GPI anchor moieties are essential for parasite survival. The paras ite GPI anchors can activate signaling pathways ill host cells, and thereby induce the expression of inflammatory cytokines, adhesion molecules and in duced nitric oxide synthase (iNOS). This might cause erythrocyte sequestrat ion, hypoglycemia, triglyceride lipogenesis and immune dysregulation. Thus, the parasite GPI anchor structure and biosynthetic pathways are attractive targets for antimalarial and/or antiparasite drug development, as discusse d here by Channe Gowda and Eugene Davidson.