Plasmodium dihydrofolate reductase is a second enzyme target for the antimalarial action of triclosan

Elizabeth Bilsland, Liisa van Vliet, Kevin Williams, Jack Feltham, Marta P. Carrasco, Wesley L. Fotoran, Eliana F. G. Cubillos, Gerhard Wunderlich, Morten Grøtli, Florian Hollfelder, Victoria Jackson, Ross D. King, Stephen G. Oliver

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)
169 Downloads (Pure)

Abstract

Malaria, caused by parasites of the genus Plasmodium, leads to over half a million deaths per year, 90% of which are caused by Plasmodium falciparum. P. vivax usually causes milder forms of malaria; however, P. vivax can remain dormant in the livers of infected patients for weeks or years before re-emerging in a new bout of the disease. The only drugs available that target all stages of the parasite can lead to severe side effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; hence, there is an urgent need to develop new drugs active against blood and liver stages of the parasite. Different groups have demonstrated that triclosan, a common antibacterial agent, targets the Plasmodium liver enzyme enoyl reductase. Here, we provide 4 independent lines of evidence demonstrating that triclosan specifically targets both wild-type and pyrimethamine-resistant P. falciparum and P. vivax dihydrofolate reductases, classic targets for the blood stage of the parasite. This makes triclosan an exciting candidate for further development as a dual specificity antimalarial, which could target both liver and blood stages of the parasite
Original languageEnglish
Article number1038
JournalScientific Reports
Volume8
Issue number1
Early online date18 Jan 2018
DOIs
Publication statusPublished - 18 Jan 2018

Keywords

  • Andes
  • Argentina
  • Chile
  • climate change
  • ENSO
  • MOD10A1
  • MODIS
  • snow albedo
  • snow cover extent
  • time series analysis
  • Enzyme Activation/drug effects
  • Triclosan/chemistry
  • Molecular Conformation
  • Models, Molecular
  • Structure-Activity Relationship
  • Tetrahydrofolate Dehydrogenase/chemistry
  • Protein Binding
  • Plasmodium/drug effects
  • Antimalarials/chemistry
  • Binding Sites
  • Folic Acid Antagonists/chemistry

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