AUTHOR=Gomes Pollyanna Stephanie , Tanghe Scott , Gallego-Delgado Julio , Conde Luciana , Freire-de-Lima Leonardo , Lima Ana Carolina , Freire-de-Lima Célio Geraldo , Lima Junior Josué da Costa , Moreira Otacílio , Totino Paulo , Rodriguez Ana , Todeschini Adriane Regina , Morrot Alexandre 

TITLE=Targeting the Hexosamine Biosynthetic Pathway Prevents Plasmodium Developmental Cycle and Disease Pathology in Vertebrate Host

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00305

DOI=10.3389/fmicb.2019.00305

ISSN=1664-302X

ABSTRACT=<p>Cerebral malaria (CM) is a clinical syndrome involving irreversible and lethal signs of brain injury associated to infection by parasites of the genus <italic>Plasmodium</italic>. 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 <italic>Plasmodium</italic> 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 <italic>Plasmodium</italic> transmission to mosquitoes. These findings point to a potential use of DON in combination therapies against malaria.</p>