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TARGETING THE HEXOSAMINE BIOSYNTHETIC PATHWAY PREVENTS PLASMODIUM DEVELOPMENTAL CYCLE AND DISEASE PATHOLOGY IN VERTEBRATE HOST
Gomes, Pollyanna Stephanie et al. | Date Issued: 2019
Author
Gomes, Pollyanna Stephanie
Tanghe, Scott
Gallego-Delgado, Julio
Conde, Luciana
Lima, Leonardo Freire de
Lima, Ana Carolina
Lima, Célio Geraldo Freire de
Lima Junior, Josué da Costa
Moreira, Otacílio
Totino, Paulo
Rodriguez, Ana
Todeschini, Adriane Regina
Morrot, Alexandre
Affilliation
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.
New York University School of Medicine. Department of Microbiology. Division of Parasitology. New York, NY, USA.
New York University School of Medicine. Department of Microbiology. Division of Parasitology. New York, NY, USA.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
New York University School of Medicine. Department of Microbiology. Division of Parasitology. New York, NY, USA.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Glicobiologia Estrutural e Funcional. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.
Abstract
Cerebral malaria (CM) is a clinical syndrome involving irreversible and lethal signs of brain injury associated to infection by parasites of the genus Plasmodium. 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 Plasmodium 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 Plasmodium transmission to mosquitoes. These findings point to a potential use of DON in combination therapies against malaria.
Keywords in Portuguese
Plasmodium falciparum
Glicobiologia
Malária cerebral
Estratégias de tratamento
Parasitas
 
Keywords
Plasmodium falciparum
Glycobyology
Cerebral malaria
Treatment strategies
Parasites
 
Publisher
Frontiers Media
Citation
GOMES, Pollyanna Stephanie et al. Targeting the Hexosamine Biosynthetic Pathway Prevents Plasmodium Developmental Cycle and Disease Pathology in Vertebrate Host. Frontiers in Microbiology, v. 10, p. 1-9, Feb. 2019.
DOI
10.3389/fmicb.2019.00305
ISSN
1664-302X