Epigenetics of malaria parasite nutrient uptake, but why?

Trends Parasitol. 2022 Aug;38(8):618-628. doi: 10.1016/j.pt.2022.05.005. Epub 2022 May 28.

Abstract

The conserved plasmodial surface anion channel (PSAC) mediates nutrient uptake by bloodstream malaria parasites and is an antimalarial target. This pathogen-associated channel is linked to the clag multigene family, which is variably expanded in Plasmodium spp. Member genes are under complex epigenetic regulation, with the clag3 genes of the human P. falciparum pathogen exhibiting monoallelic transcription and mutually exclusive surface exposure on infected erythrocytes. While other multigene families use monoallelic expression to evade host immunity, the reasons of epigenetic control of clag genes are unclear. I consider existing models and their implications for nutrient acquisition and immune evasion. Understanding the reasons for epigenetic regulation of PSAC-mediated nutrient uptake will help clarify host-pathogen interactions and guide development of therapies resistant to allele switching.

Keywords: antimalarial drug discovery; epigenetic regulation; ion channel; malaria parasite antigens; membrane transport; nutrient acquisition.

Publication types

  • Review
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Epigenesis, Genetic* / genetics
  • Epigenesis, Genetic* / physiology
  • Erythrocytes / parasitology
  • Humans
  • Malaria* / parasitology
  • Malaria, Falciparum* / genetics
  • Malaria, Falciparum* / metabolism
  • Nutrients / metabolism
  • Plasmodium falciparum* / genetics
  • Plasmodium falciparum* / metabolism
  • Plasmodium* / genetics
  • Plasmodium* / metabolism
  • Protozoan Proteins / metabolism

Substances

  • Protozoan Proteins