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Targeting the Hexosamine Biosynthetic Pathway Prevents Plasmodium Developmental Cycle and Disease Pathology in

Pollyanna Stephanie Gomes1, Scott Tanghe2, Julio Gallego-Delgado2

  • 1Centro de Pesquisas em Tuberculose, Instituto de Microbiologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Frontiers in Microbiology
|March 16, 2019
PubMed

Insights

6-Diazo-5-oxo-L-norleucine (DON) aids recovery in experimental cerebral malaria (CM) by reducing parasite levels. This therapeutic approach also significantly lowers malaria parasite transmission to mosquitoes.

Area of Science:

  • Infectious diseases
  • Parasitology
  • Neuroscience

Background:

  • Cerebral malaria (CM) is a severe clinical syndrome caused by Plasmodium parasites, leading to lethal brain injury.
  • Pathogenesis involves infection-induced proinflammatory cytokines and cytoadherence of infected red blood cells in cerebral microvasculature.
  • Parasitic glycoconjugates are crucial virulence factors in Plasmodium spp. host-pathogen interactions.

Purpose of the Study:

  • To investigate the therapeutic potential of 6-Diazo-5-oxo-L-norleucine (DON) in experimental murine cerebral malaria.
  • To evaluate the impact of DON on parasite levels and transmission.

Main Methods:

  • Treatment of experimental murine cerebral malaria with 6-Diazo-5-oxo-L-norleucine (DON).
  • Assessment of therapeutic recovery and reduction in parasite load.
  • Evaluation of Plasmodium transmission to mosquitoes following DON treatment.

Main Results:

  • DON administration led to recovery in experimental murine cerebral malaria.
  • DON treatment was associated with decreased Plasmodium parasitism.
  • Reduced parasitism significantly lowered malaria parasite transmission to mosquitoes.

Conclusions:

  • 6-Diazo-5-oxo-L-norleucine (DON) demonstrates therapeutic efficacy in experimental cerebral malaria.
  • DON treatment reduces parasite burden and subsequent transmission, suggesting a dual benefit.
  • DON represents a potential candidate for combination therapies against malaria.
Keywords:
Plasmodium falciparumcerebral malariaglycobyologyparasitestreatment strategies

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