Targeting the Hexosamine Biosynthetic Pathway Prevents Developmental Cycle and Disease Pathology in Vertebrate Host.

Cerebral malaria (CM) is a clinical syndrome involving irreversible and lethal signs of brain injury associated to infection by parasites of the genus . The pathogenesis of CM derives from infection-induced proinflammatory cytokines associated with cytoadherence of parasitized red blood cells to brain microvasculature. Glycoconjugates are very abundant in the surface of spp., and are critical mediators of parasite virulence in host-pathogen interactions. Herein, we show that 6-Diazo-5-oxo-L-norleucine (DON) therapeutically used for blocking hexosamine biosynthetic pathway leads to recovery in experimental murine cerebral malaria. DON-induced protection was associated with decreased parasitism, which severely reduced transmission to mosquitoes. These findings point to a potential use of DON in combination therapies against malaria.