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The Wellcome Trust lecture. Mechanisms of molecular trafficking in malaria

I W Sherman1

  • 1Department of Biology, University of California, Riverside 92521.

Parasitology
|January 1, 1988
PubMed

Insights

Malaria parasite Plasmodium alters red blood cell permeability, affecting nutrient and drug transport. Future research needs controlled conditions to understand these complex transport mechanisms.

Area of Science:

  • * Molecular biology
  • * Parasitology
  • * Cell biology

Background:

  • * The asexual stages of Plasmodium parasites reside within erythrocytes (red blood cells).
  • * Plasmodium infection induces significant changes in the permeability of the host red blood cell membrane.
  • * These permeability alterations affect the transport of essential nutrients, ions, and antimalarial drugs.

Purpose of the Study:

  • * To investigate the mechanisms underlying altered red blood cell permeability during malaria infection.
  • * To differentiate between transporter modification and the formation of leaks/pores as causes of increased influx.
  • * To identify the specific transport systems operational in malaria-infected erythrocytes.

Main Methods:

  • * Analysis of red blood cell permeability changes for various solutes and drugs.
  • * Examination of red cell transporters' affinity and specificity.
  • * Investigation of parasite-encoded transporter insertion and aqueous leak formation.

Main Results:

  • * Increased influx of glucose, amino acids, purine nucleosides, ions (Na+, K+, Ca2+, Zn2+, Fe2+), and antimalarial drugs (chloroquine, amodiaquine, mefloquine) was observed.
  • * Changes in permeability are generally not attributed to altered affinity or specificity of host red cell transporters.
  • * Most transport changes are not dependent on the insertion of Plasmodium proteins, suggesting leak formation.
  • * A striking increase in influx suggests parasite-encoded transporters or aqueous leaks/pores.

Conclusions:

  • * Plasmodium infection significantly modifies red blood cell permeability, impacting nutrient and drug uptake.
  • * The precise mechanisms, whether transporter-mediated or leak-based, require further elucidation.
  • * Future studies necessitate rigorous experimental conditions to distinguish between various transport systems in infected erythrocytes.

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