| Popis: |
Summary: Folate metabolism is essential for DNA synthesis and a validated drug target in fast-growing cell populations, including tumors and malaria parasites. Genome data suggest that Plasmodium has retained its capacity to generate folates de novo. However, the metabolic plasticity of folate uptake and biosynthesis by the malaria parasite remains unresolved. Here, we demonstrate that Plasmodium uses an aminodeoxychorismate synthase and an aminodeoxychorismate lyase to promote the biogenesis of the central folate precursor para-aminobenzoate (pABA) in the cytoplasm. We show that the parasite depends on de novo folate synthesis only when dietary intake of pABA by the mammalian host is restricted and that only pABA, rather than fully formed folate, is taken up efficiently. This adaptation, which readily adjusts infection to highly variable pABA levels in the mammalian diet, is specific to blood stages and may have evolved to avoid folate competition between the parasite and its host. : Matz et al. present an integrated approach of experimental genetics and nutritional metabolite restriction to demonstrate two complementary folate acquisition strategies of the malaria parasite in the blood: endogenous synthesis and salvage of the folate precursor pABA. Uptake of pABA, and not folate, is physiological, facilitating avoidance of host-parasite competition. Keywords: para-aminobenzoic acid, pABA, folate, aminodeoxychorismate synthase, aminodeoxychorismate lyase, ADCS, ADCL, milk, malaria, Plasmodium |
